Isoliquiritigenin regulates the circ_0002860/miR-431-5p/RAB9A axis to function as a tumor inhibitor in melanoma

Background: Isoliquiritigenin (ISL) presents antitumor effects against melanoma cells. It is known that various circular RNAs (circRNAs) are involved in the development of melanoma. Therefore, the present study aims to investigate the molecular mechanisms of ISL and circ_0002860. Methods: Circ_0002860, microRNA-431-5p (miR-431-5p) and member RAS oncogene family (RAB9A) were detected through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay. Cell viability was examined via cell counting kit-8 assay. The proliferation ability was assessed using colony formation assay. Cell apoptosis and cell cycle were determined by flow cytometry. Transwell assay was used for detection of migration and invasion. Western blot was conducted for protein analysis. Target binding was confirmed via dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo research was performed through xenograft tumor assay. Results: Circ_0002860 was downregulated by ISL in melanoma cells. ISL-induced inhibitory effects on cell proliferation, cell cycle progression, migration and invasion were alleviated by circ_0002860 overexpression. MiR-431-5p was a target of circ_0002860. Circ_0002860 eliminated the ISL-induced tumor inhibition via sponging miR-431-5p in melanoma cells. Circ_0002860 elevated the RAB9A level by targeting miR-431-5p. The function of ISL was related to miR-431-5p/RAB9A axis in melanoma progression. Tumor growth was reduced by ISL in vivo through downregulating circ_0002860 to regulate miR-431-5p and RAB9A levels. Conclusion: The current data indicates that ISL suppressed cell malignant progression of melanoma via targeting the circ_0002860/miR-431-5p/RAB9A pathway.(AU)

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.

Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.

Bioactive properties of Persea lingue Ness (Lauraceae) fruit and leaf extracts / Propriedades bioativas de extratos de folhas e frutos de Persea lingue Ness (Lauraceae)

Persea lingue Ness is a tree species that lives mainly in temperate forests of south-central Chile. Its leaves are used in ethnomedicine, the fruit is a drupe similar to that of the avocado and has not been studied. The aim of this study was to determine the cytotoxicity in leukemia cell and antibacterial activity, along with some chemical content characteristics of P. lingue fruit and leaf extracts. The antibacterial activity was determined by the inhibition of bacterial growth in liquid medium assay against Gram-positive and Gram-negative bacteria. The leukemia cell lines Kasumi-1 and Jurkat were used to evaluate the cytotoxic activity by using propidium iodide and AlamarBlue assays. Total phenolic, flavonoid, condensed tannin, alkaloid and lipid contents were evaluated in the fruit and in the leaf extracts. The antioxidant activity of both extracts were also elavaluated. Leaf extract presented the highest content of total phenols, condensed tannins and flavonoids, and also the highest antioxidant activity. While the fruit extract has a higher amount of lipids and alkaloids and the high antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium and Micrococcus luteus. The leaf extract only showed activity against M. luteus. Concerning the cytotoxic activity, only the fruit extract showed cytotoxicity against the cell lines Jurkat and Kasumi-1. P. lingue fruit extract is a potential source of biologically active molecules for the development of new drugs to be used in some types of leukemia, as well as antibacterial agent.(AU)

Persea lingue Ness é uma árvore que vive principalmente na floresta temperada do centro-sul do Chile. As folhas são usadas na etnomedicina. O fruto é uma drupa similar ao abacate e que nunca foi pesquisada anteriormente. O objetivo deste estudo foi o de avaliar a citotoxicidade em células leucêmicas e as atividades antibacterianas, assim como algumas características químicas do extrato de fruto e da folha do P. lingue. As atividades antibacterianas foram determinadas pelo método da inibição do crescimento bacteriano em meio líquido empregando-se bactérias Gram-positivas e Gram-negativas. As linhagens celulares leucêmicas, Kasumi-1 e Jurkat foram usadas para avaliar a atividade citotóxica em ensaios empregando-se iodeto de propídio e AlamarBlue. Foram avaliados os teores totais de fenóis, flavonóides, taninos condensados, alcalóides e lipídeos presentes nos extratos das folhas e dos frutos. As atividades antioxidantes de ambos os extratos também foram avaliadas. O extrato das folhas foi o que apresentou o maior conteúdo de fenóis, taninos condensados e flavonóides totais e a maior atividade antioxidante. Já o extrato de fruto apresentou a maior quantidade de lipídios e alcaloides e a melhor atividade antibacteriana contra Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus megaterium e Micrococcus luteus. Já o extrato das folhas apresentou apenas atividade contra M. luteus. Em relação à atividade citotóxica, apenas o extrato do fruto apresentou citotoxicidade contra as linhagens celulares Jurkat e Kasumi-1. Em resumo, o extrato do fruto de P. lingue é uma potencial fonte de moléculas com atividade biológica para o desenvolvimento de novos fármacos a serem utilizados em alguns tipos de leucemia, bem como agente antibacteriano.(AU)

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.(AU)

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.(AU)

Potential use of bacterial pigments as anticancer drugs and female reproductive toxicity: a review / Uso potencial de pigmentos bacterianos como drogas anticâncer e toxicidade reprodutiva feminina: uma revisão

Natural bioactive compounds obtained from microorganisms, have awakened particular interest in the industry nowadays. This attention comes when natural resources depletion is pronounced, and the acquisition of both new plant origin resources and bioactive products, represents a challenge for the next generations. In this sense, prospecting for large-scale production and use of bacterial pigments is a necessary strategy for the development of novel products. A wide variety of properties have been attributed to these substances and, among them, their therapeutic potential against important diseases, such as cancer. There is consensus that available chemotherapy protocols are known to detrimentally affect cancer patients fertility. Hence, considerable part of the deleterious effects of chemotherapy is related to the drugs cytotoxicity, which, in addition to cancer cells, also affect normal cells. Therefore, the intrinsic properties of bacterial pigments associated with low cytotoxicity and relevant cell selectivity, certified them as potential anticancer drugs. However, little information is available about reproductive toxicity of these new and promising compounds. Thus, the present review aims to address the main bacterial pigments, their potential uses as anticancer drugs and their possible toxic effects, especially on the female gonad.

Os compostos bioativos naturais obtidos de microrganismos têm despertado especial interesse da indústria nos últimos anos. Esta atenção ocorre em um momento em que o esgotamento de recursos naturais é pronunciado, e a aquisição de novos insumos e produtos bioativos de origem vegetal representa um desafio para as próximas gerações. Neste sentido, a prospecção para a produção e uso em larga escala dos pigmentos bacterianos tem representado uma importante estratégia para o desenvolvimento de novos produtos. Uma grande variedade de propriedades foi atribuída a estas substâncias, entre elas, o potencial terapêutico contra doenças importantes, como o câncer. Existe um consenso de que os protocolos quimioterápicos disponíveis são conhecidos por afetarem negativamente a fertilidade de pacientes com câncer. Grande parte dos efeitos deletérios da quimioterapia está relacionado à citotoxicidade das drogas usadas para este fim, que além das células cancerosas, afetam as células normais. Nesse sentido, as propriedades naturais atribuídas aos pigmentos bacterianos associadas à baixa citotoxicidade e relevante seletividade, os qualificaram como potenciais drogas anticâncer. No entanto, pouco se tem de informação a respeito da toxicidade reprodutiva destes novos e promissores compostos. Dessa forma, a presente revisão tem o objetivo de abordar os principais pigmentos bacterianos, suas utilizações potenciais como drogas anticâncer, bem como os seus possíveis efeitos tóxicos, sobretudo, sobre a gônada feminina.

Recycled pequi (Caryocar brasiliense, Camb) shell ethanolic extract induces apoptosis in canine osteosarcoma cell / Extrato etanólico de cascas recicladas de pequi (Caryocar brasiliense, Camb) induz apoptose em células de osteossarcoma canino

Osteosarcoma is a mesenchymal cancer associated with high mortality in dogs and in humans. The biodiversity-rich Cerrado, the predominant biome in the Midwest region of Brazil, is native to locally appreciated fruits such as pequi (Caryocar brasiliense, Camb). Although this plant has been frequently used in folk medicine, the pharmacological properties of pequi fruit shells have not been fully evaluated. Thus, this study aimed to determine the cytotoxic activity of ethanol extract of recycled pequi shells on canine osteosarcoma cells in vitro. Cells were cultured and treated with final extract concentrations of 0, 0.029 µg/µL, 0.29 µg/µL, and 2.91 µg/µL for 24, 48, or 72 hours. Cell viability assay using trypan blue exclusion method and tetrazolium reduction method, cell survival assay, and double labeling with annexin V and propidium iodide were performed in the treated osteosarcoma cells. These allowed the determination of IC50, survival fraction, and type of cell death, respectively. Pequi shell ethanol extract at a concentration of 2.91 µg/µL showed the greatest inhibition of osteosarcoma cell growth in vitro, resulting in a 71.80% decrease in growth compared to the control. The mean IC50 was 155.2 µg/mL at 72 hours. The calculated survival fractions showed that cell growth at 72 hours was 3.33% lower in cells treated with 2.91 µg/µL extract. Results from the double labeling experiment suggest that apoptosis was the predominant type of cell death in cells treated with 2.91 µg/µL extract. These results demonstrate that ethanol extract of recycled pequi shells promotes apoptosis in canine osteosarcoma cells.

O osteossarcoma é uma neoplasia mesenquimal associada à alta mortalidade em cães e humanos. O pequi (Caryocar brasiliense, Camb.) é nativo do Cerrado, bioma rico em biodiversidade predominante na região Centro-Oeste do Brasil. Embora esta planta seja frequentemente utilizada na medicina popular, as propriedades farmacológicas da casca do pequi ainda são pouco conhecidas. Este estudo teve como objetivo determinar a atividade citotóxica do extrato etanólico de cascas de pequi recicladas em células de osteossarcoma canino. As células foram cultivadas e tratadas com concentrações finais de extrato de zero, 0,029 µg/µL, 0,29 µg/µL e 2,91 µg/µL por 24, 48 ou 72 horas. As células foram submetidas a ensaio de viabilidade celular pelos métodos de exclusão de azul de tripano da redução de tetrazólio para determinar a IC50, ao ensaio de sobrevivência celular para calcular a fração de sobrevivência e à dupla marcação com anexina V e iodeto de propídio para determinar o tipo de morte celular. O extrato etanólico de casca de pequi na concentração de 2,91 µg/µL apresentou a maior inibição do crescimento de células de osteossarcoma, com redução de 71,80% no crescimento em relação ao controle. A IC50 média foi de 155,2 µg/mL em 72 horas. O crescimento celular em 72 horas foi 3,33% menor nas células tratadas com 2,91 µg/µL de extrato. A apoptose foi o tipo predominante de morte celular em células tratadas com 2,91 µg/µL de extrato. Esses resultados demonstram que o extrato etanólico de cascas de pequi recicladas promove apoptose em células de osteossarcoma canino.

Mastocitoma cutâneo em uma cadela / Cutaneous mast cell tumor in a bitch

Background: The diagnostic of neoplasia in dogs has risen significantly in the last years and this fact is mostly attributed to the longer life expectancy of these animals, which contributes to a greater chance of exposure to carcinogenic agents. In between the diverse tumors that could compromise skin, the mastocytoma is the third most commonly diagnosed neoplasia. It is characterized by being a form of neoplasia with round cells, these being the mast cells. The objective of the present study consisted in relating a case of cutaneous mastocytoma in a 7-year-old bitch mixed-breed treated at the Veterinary Medical Teaching Hospital of the University of Uberaba (UNIUBE) - Uberaba, MG, Brazil. Case: The bitch initially presented a localized nodule external to the right ear pinna with cytology test suggesting a mastocytoma. The nodule was surgically removed and, posteriorly, an histopatholgy was not requested. After 5 months since the emergence of the nodule and a month after its surgical resection, the tutor noticed the presence of a new growth in the ipsilateral cervical region to the previous nodule. At this moment, the responsible veterinarian decided to refer the animal to an oncologist. During the appointment with the oncologist, alterations such as hyporexia and anemia were related, and the presence of a nodule in the right cervical region measuring 4.5 to 4 cm of diameter was verified. Material for cytologic evaluation of the neoplasia was collected and again the result suggested a mastocytoma. The new tumor was also surgically removed but was then referred to histopathological evaluation for diagnostic confirmation, grading and evaluation of surgical margins. The tumor was classified as an infiltrative subcutaneous mastocytoma presenting, additionally, compromised surgical margins. After its excision, the association with a chemotherapy treatment using a protocol of Vimblastina 2 mg/m², i.v. in unique dosage per section, associated with Predinisona 1 mg/kg, v.o, SID was indicated. Each section was realized with an interval of 7 days in between. Only 2 chemotherapy sessions took place. Because of the worsening of the clinical condition associated with a very weakened animal the veterinarian opted for the euthanasia of the animal. Discussion: The diagnostic of mastocytoma must be realized through the association of cytology and histopathology, in case histopathological evaluation is needed to confirm the obtained cytology result, to grade the tumor and to evaluate the compromising of surgical margins. In this sense, it was observed that the bitch was submitted only to cytology diagnostic when it presented the nodule in the ear pavilion. Yet, at the second approach realized by the oncologist, it was possible to realize adequate diagnose methods. However, the animal was not submitted to clinical staging of the mastocytoma due to the non-authorization of the exam by the tutor. Such measure is very important, as it reflects directly in the treatment and prognostic of the animal. Thus, image exams such as abdominal ultrasonography and chest X-ray should have been realized, as well as cytological and histopathological evaluation of the regional lymph nodes, in order to search for metastasis points in these places. As the data suggests, the importance of clinical staging of animals affected by this neoplasia and the importance of cytological evaluation associated with histopathology for a correct diagnosis, prognosis and mastocytoma treatment is noted. It is emphasized that many times veterinarians face impediment related to requesting all necessary exams coming from tutors, which compromises treatment success.

Studies on the recombinant production and anticancer activity of thermostable L- asparaginase I from Pyrococcus abyssi / Estudos sobre a produção recombinante e atividade anticancerígena da L-asparaginase I termoestável de Pyrococcus abyssi

L-Asparaginase catalysing the breakdown of L-Asparagine to L-Aspartate and ammonia is an enzyme of therapeutic importance in the treatment of cancer, especially the lymphomas and leukaemia. The present study describes the recombinant production, properties and anticancer potential of enzyme from a hyperthermophilic archaeon Pyrococcus abyssi. There are two genes coding for asparaginase in the genome of this organism. A 918 bp gene encoding 305 amino acids was PCR amplified and cloned in BL21 (DE3) strain of E. coli using pET28a (+) plasmid. The production of recombinant enzyme was induced under 0.5mM IPTG, purified by selective heat denaturation and ion exchange chromatography. Purified enzyme was analyzed for kinetics, in silico structure and anticancer properties. The recombinant enzyme has shown a molecular weight of 33 kDa, specific activity of 1175 U/mg, KM value 2.05mM, optimum temperature and pH 80°C and 8 respectively. No detectable enzyme activity found when L-Glutamine was used as the substrate. In silico studies have shown that the enzyme exists as a homodimer having Arg11, Ala87, Thr110, His112, Gln142, Leu172, and Lys232 being the putative active site residues. The free energy change calculated by molecular docking studies of enzyme and substrate was found as ∆G ­ 4.5 kJ/mole indicating the affinity of enzyme with the substrate. IC50 values of 5U/mL to 7.5U/mL were determined for FB, caco2 cells and HepG2 cells. A calculated amount of enzyme (5U/mL) exhibited 78% to 55% growth inhibition of caco2 and HepG2 cells. In conclusion, the recombinant enzyme produced and characterized in the present study offers a good candidate for the treatment of cancer. The procedures adopted in the present study can be prolonged for in vivo studies.

A L-asparaginase, que catalisa a degradação da L-asparagina em L-aspartato e amônia, é uma enzima de importância terapêutica no tratamento do câncer, especialmente dos linfomas e da leucemia. O presente estudo descreve a produção recombinante, propriedades e potencial anticancerígeno da enzima de Pyrococcus abyssi, um archaeon hipertermofílico. Existem dois genes que codificam para a asparaginase no genoma desse organismo. Um gene de 918 bp, que codifica 305 aminoácidos, foi amplificado por PCR e clonado na cepa BL21 (DE3) de E. coli usando o plasmídeo pET28a (+). A produção da enzima recombinante foi induzida sob 0,5mM de IPTG, purificada por desnaturação seletiva por calor e cromatografia de troca iônica. A enzima purificada foi analisada quanto à cinética, estrutura in silico e propriedades anticancerígenas. A enzima recombinante apresentou peso molecular de 33 kDa, atividade específica de 1.175 U / mg, valor de KM 2,05 mM, temperatura ótima de 80º C e pH 8. Nenhuma atividade enzimática detectável foi encontrada quando a L-glutamina foi usada como substrato. Estudos in silico mostraram que a enzima existe como um homodímero, com Arg11, Ala87, Thr110, His112, Gln142, Leu172 e Lys232 sendo os resíduos do local ativo putativo. A mudança de energia livre calculada por estudos de docking molecular da enzima e do substrato foi encontrada como ∆G ­ 4,5 kJ / mol, indicando a afinidade da enzima com o substrato. Valores de IC50 de 5U / mL a 7,5U / mL foram determinados para células FB, células caco2 e células HepG2. Uma quantidade de enzima (5U / mL) apresentou inibição de crescimento de 78% a 55% das células caco2 e HepG2, respectivamente. Em conclusão, a enzima recombinante produzida e caracterizada no presente estudo é uma boa possibilidade para o tratamento do câncer. Os procedimentos adotados na presente pesquisa podem ser aplicados para estudos in vivo.

Avaliação morfológica e morfométrica do útero de camundongos fêmeas após uso de extrato de graviola / Morphological and morphometric evaluation of femal e mice uterus after using soursop extract

O presente estudo teve como objetivo avaliar o efeito do extrato de Annona muricata no útero de camundongos fêmeas por meio de análises macro e microscópicas. Vinte camundongos fêmeas foram aleatoriamente distribuídas em quatro grupos: controle (solução salina), ciclofosfamida e extrato de folhas de graviola em duas concentrações diferentes (50 e 100mg/kg). Após sete dias de experimento, as fêmeas foram eutanasiadas e seus úteros coletados e submetidos a análise macroscópica, seguida de processamento histológico para análises morfológicas e morfométricas das camadas do útero e das glândulas endometriais. As características macroscópicas do útero foram mantidas em todos os grupos avaliados. Microscopicamente, não foram identificadas alterações patológicas nas células uterinas. No entanto, houve um aumento significativo na camada do miométrio após o tratamento com ciclofosfamida (p<0,05). O diâmetro interno das glândulas endometriais foi significativamente menor em ambos os grupos tratados com extrato de A. muricata quando comparados ao grupo controle (p<0,05), enquanto o diâmetro total das glândulas foi significativamente menor somente na maior concentração de extrato de A. muricata quando comparado ao grupo controle (p<0,05). A administração do extrato de folhas de A. muricata não causou alterações morfológicas ao útero. Desta forma, o extrato não apresentou toxicidade uterina nas condições avaliadas.

O presente estudo teve como objetivo avaliar o efeito do extrato de Annona muricata no útero de camundongos fêmeas por meio de análises macro e microscópicas. Vinte camundongos fêmeas foram aleatoriamente distribuídas em quatro grupos: controle (solução salina), ciclofosfamida e extrato de folhas de graviola em duas concentrações diferentes (50 e 100mg/kg). Após sete dias de experimento, as fêmeas foram eutanasiadas e seus úteros coletados e submetidos a análise macroscópica, seguida de processamento histológico para análises morfológicas e morfométricas das camadas do útero e das glândulas endometriais. As características macroscópicas do útero foram mantidas em todos os grupos avaliados. Microscopicamente, não foram identificadas alterações patológicas nas células uterinas. No entanto, houve um aumento significativo na camada do miométrio após o tratamento com ciclofosfamida (p<0,05). O diâmetro interno das glândulas endometriais foi significativamente menor em ambos os grupos tratados com extrato de A. muricata quando comparados ao grupo controle (p<0,05), enquanto o diâmetro total das glândulas foi significativamente menor somente na maior concentração de extrato de A. muricata quando comparado ao grupo controle (p<0,05). A administração do extrato de folhas de A. muricata não causou alterações morfológicas ao útero. Desta forma, o extrato não apresentou toxicidade uterina nas condições avaliadas.

Foeniculum vulgare (fennel) and Cymbopogon winterianus (citronella) essential oils to replace a growth promoter in the diet of European quails / Óleos essenciais de Foeniculum vulgare (erva doce) e Cymbopogon winterianus (citronela) em substituição a um promotor de crescimento na dieta de codornas europeias

The objective of this study was to evaluate the replacement of a growth-promoting antibiotic by fennel (Foeniculum vulgare) and citronella (Cymbopogon winterianus) essential oils in the quail diet on performance variables (weight gain, feed intake, feed conversion), as well as the carcass and cut yield. To do so, 240 one-day-old male and female European quails were distributed in a completely randomized design with four treatments, five replications and 12 animals per experimental unit. The treatments consisted of: PC ­ positive control diet without fennel or citronella essential oils and with the growth promoter (zinc bacitracin); NC ­ negative control diet without essential oils and without growth promoter; CEO - Diet with +0.078% citronella essential oil without the growth promoter; and FEO - Diet with +0.078% fennel essential oil without the growth promoter. The experiment lasted 42 days, in which the performance variables were analyzed in three periods (1-14 days; 14-21 days; and 22-42 days) and the carcass and cut yield in two periods (at 21 and 42 days). The observed data were submitted to analysis of variance and the comparison of means was performed using the Tukey's test at 5% significance. The presence of essential oils positively influenced (P<0.05) the performance variables and the carcass and cuts yield in all analyzed periods. The use of fennel and citronella essential oils to replace zinc bacitracin in the diet of European quails improves performance and the carcass and cut yield.(AU)

Objetivou-se avaliar a substituição de um antibiótico promotor de crescimento por óleos essenciais de erva-doce (Foeniculum vulgare) e citronela (Cymbopogon winterianus) na dieta de codornas sobre o desempenho, rendimento de carcaça e cortes. Para isso, foram utilizadas 240 codornas europeias machos e fêmeas de um dia de idade distribuídos em delineamento inteiramente ao acaso com quatro tratamentos, cinco repetições e 12 animais por unidade experimental. Os tratamentos consistiram em: CP- Dieta sem os óleos essenciais de erva-doce ou citronela e com o promotor de crescimento (bacitracina de zinco); CN- Dieta sem os óleos essenciais e sem o promotor de crescimento; OC- Dieta com + 0,078% de óleo essencial de citronela sem o promotor de crescimento; OED- Dieta com + 0,078% de óleo essencial de erva-doce sem o promotor de crescimento. O experimento teve duração de 42 dias, no qual as variáveis de desempenho foram analisadas em três períodos (1-14 dias; 14-21 dias e 22-42 dias) e o rendimento de carcaça e cortes em dois períodos (aos 21 e 42 dias). Os dados observados foram submetidos à análise de variância e a comparação das médias foi realizada pelo teste de Tukey a 5%. A presença dos óleos essenciais influenciou positivamente (P<0,05) as variáveis de desempenho e o rendimento de carcaça e cortes em todos os períodos analisados. A utilização de óleos essenciais de erva-doce e citronela em substituição a bacitracina de zinco na dieta de codornas europeias melhora o desempenho e o rendimento de carcaça e cortes.(AU)

Canine mast cell tumour lomustine's sensitization by tyrosine kinase inhibitors

Background: Tyrosine kinase inhibitors (TKIs) may sensitize neoplasms to conventional antineoplastic agents, however such studies are scarse in the veterinary literature and there is no in vivo study about this subject. Although the literature recommend consensual about the use of masitinib for unresectable or metastatic MCTs, the potential of tumour sensitization to chemotherapeutic agents exerted by the drug is poorly explored in veterinary medicine. The objective of this paper was to report, for the first time, the sensitization of 2 canine mast cell tumours (MCTs) to lomustine, with the use of 2 tyrosine kinase inhibitors: masitinib and toceranib. Cases: Two dogs were referred due tumour recurrence in the left pelvic limb (dog 1), and unilateral mass in the right nasal mucocutaneous region (dog 2). The first case was a 8-year-old female Pinscher, and the second case refers to a 8-year-old male mixed-breed dog. Fine needle aspiration of both lesions was performed, and the cytological analysis were compatible with high grade canine MCT. In the first case, it was started a chemotherapeutic treatment with intravenous vinblastine (2 mg/m² ), associated with prednisolone (40 mg/m2 , every 24 h for 7 days), followed by 25 mg/m2 every 24 h, for more 30 days, tramadol (4 mg/kg every 8 h, until new recommendations) and gabapentin (3 mg/kg every 12 h, until new recommendations). However, there was no objective response, and vinblastine was substituted by lomustine (60 mg/m2 every 21 days), however there was also no response after 2 doses. After masitinib importation, the same was started at 12.5 mg/kg orally every 24 h, but there was also no objective response. However, after new lomustine administration the lesion showed complete remission. The second dog initiated its treatment with toceranib, recently licensed in Brazil, at a dosage of 2.7 mg/kg every 48 h, and after 30 days, there was partial remission. However, the remaining lesion still deemed unresectable, and systemic chemotherapy with lomustine (50 mg/m2 ) was initiated along with continuous toceranib. After 3 weeks of the first chemotherapy complete remission was noted and a second dose was administered. Once the patient remained in complete clinical remission, only toceranib was maintained at the same dose. After 11 months using the toceranib, there was sign of disease recurrence and lomustine was re-initiated resulting in complete remission. Discussion: The TKIs masitinib and toceranib might be considered the first-line therapy for unresectable and/or metastatic canine MCT, but also for those cases with confirmed internal tandem duplications in the exon 11 of the c-KIT protooncogene. Masitinib appears to be more selective than others TKI, such as toceranib, imatinib, dasatinib and sunitinib, because it causes weak inhibition of BCR/ABL (breakpoint cluster region-Abelson), Fms (macrophage colony-stimulating factor receptor), Flt-3 (FMS-like tyrosine kinase-3) and VEGFR (vascular endothelial growth factor receptor), which may partially explains its increased safety and lower risk of cardiotoxicity. In the first case, the animal has been treated with lomustine associated to masitinib and showed a progression-free interval of 33 days, however, the response reported may have been lower, due previously exposition to chemotherapeutic agents, which might compromise the response to TKI. The second case, with the association of lomustine and toceranib, was followed up for 365 days, presenting only one recurrence in the final third of the follow-up, however, with subsequent new complete remission. Sensitization of canine MCT to lomustine with TKIs increases the therapeutic possibilities for this neoplasm, mainly in patients with advanced stage and high-grade tumours.

Phytochemical characterization and biological activities of Plectranthus barbatus Andrews / Caracterização fitoquímica e atividades biológicas de Plectranthus barbatus Andrews

Plectranthus barbatus Andrews (Lamiaceae) is widely distributed in the world and has a range of popular therapeutic indications. This work aimed to evaluate the phytochemical characterization of two leaf extracts of P. barbatus, and their antimicrobial, antineoplastic and immunomodulatory potential. After collection, herborization and obtainment of the P. barbatus aqueous extract (PBA) and acetone:water 7:3 P. barbatus organic extract (PBO), the phytochemical characterization was performed by high-performance liquid chromatography (HPLC). The antimicrobial activity was performed to determine the minimum inhibitory concentration (MIC) against eight bacterial strains using the microdilution test and the fungus Trichophyton rubrum by disc diffusion assay and microdilution test. Cytotoxicity was assessed by MTT and trypan blue methods in normal peripheral blood mononuclear cells (PBMCs) at concentrations ranged between 0.1 to 100 µg.mL-1 and in neoplastic cell lines Toledo, K562, DU-145 and PANC-1 at 1, 10 and 100 µg.mL-1 . Immunomodulatory activity, was evaluated by sandwich ELISA of proinflammatory cytokines at BALB/c mice splenocytes cultures supernatant. Both extracts presented flavonoids, cinnamic derivatives, steroids and ellagic acid. PBO showed bacteriostatic activity against Acinetobacter baumannii (MIC = 250 µg.mL-1) clinical isolate and PBA fungistatic activity against Trichophyton rubrum (MIC = 800 µg.mL-1). The extracts did not exhibit toxicity to PBMCs and neoplastic cells (IC50 > 100 µg.mL-1). Additionally, PBO at 100 µg.mL-1 significantly inhibited IFN-γ and IL-17A cytokines (p = 0.03). Plectranthus barbatus is a potential candidate for therapeutic use due to its low toxicity in healthy human cells and exhibits biological activities of medical interest as bacteriostatic, fungistatic and immunomodulatory.

Plectranthus barbatus Andrews (Lamiaceae) é amplamente distribuída no mundo e com uma série de indicações terapêuticas populares. Este trabalho teve como objetivo avaliar a caracterização fitoquímica de dois extratos da folha de P. barbatus e seu potencial antimicrobiano, antineoplásico e imunomodulador. Após coleta, herborização e obtenção do extrato aquoso (PBA) e acetona: água 7: 3 (orgânico) (PBO) de P. barbatus, a caracterização fitoquímica foi realizada por cromatografia líquida de alta eficiência (CLAE). A atividade antimicrobiana foi realizada para determinar a concentração inibitória mínima (CIM) contra oito cepas bacterianas usando o teste de microdiluição e o fungo Trichophyton rubrum por ensaio de difusão em disco e teste de microdiluição. A citotoxicidade foi avaliada por métodos MTT e azul de tripan em células normais mononucleares do sangue periférico (CMSP) em concentrações variadas entre 0,1 a 100 µg.mL-1 e nas linhagens celulares neoplásicas Toledo, K562, DU-145 e PANC-1 em 1, 10 e 100 µg.mL-1 . A atividade imunomoduladora foi avaliada por ELISA sanduíche de citocinas pró-inflamatórias em sobrenadante de culturas de esplenócitos de camundongos BALB/c. Ambos os extratos apresentaram flavonoides, derivados cinâmicos, esteróides e ácido elágico. O PBO mostrou atividade bacteriostática contra Acinetobacter baumannii (CIM = 250 µg.mL-1) e atividade fungistática do PBA contra Trichophyton rubrum (CIM = 800 µg.mL-1). Os extratos não apresentaram toxicidade para CMSP e células neoplásicas (IC50 > 100 µg.mL-1). Além disso, o PBO a 100 µg.mL-1 inibiu significativamente as citocinas IFN-γ e IL-17A (p = 0,03). Plectranthus barbatus é um candidato potencial para uso terapêutico devido à sua baixa toxicidade em células humanas saudáveis e exibe atividade de interesse médico como bacteriostática, fungistática e imunomoduladora.

Turmeric ethanol extract (Curcuma longa L. ) reduces apoptosis and promotes canine osteosarcoma cell proliferation / Extrato etanólico de açafrão (Curcuma longa L. ) reduz apoptose e promove proliferação de células de osteossarcoma canino

Curcuma longa L., also known as turmeric, has been widely studied for its various therapeutic properties, including antineoplastic action. The ethanolic extract of the plant contains several phenolic compounds, especially curcumin. Osteosarcoma is a predominant bone tumor in dogs and humans, characterized by high metastatic potential and an unfavorable prognosis. The aim of this study was to investigate the effects of turmeric ethanol extract on canine osteosarcoma cells from established culture. The cells were cultured and treated with different curcumin concentrations (0, 10 µM, 20 µM, 50 µM, 100 µM, and 1000 µM) and exposure times (24h, 48h, and 72h). We first performed tetrazolium reduction technique (MTT) assay and calculated IC50. An immunocytochemistry assay was performed after extract treatment to verify the expression of mutated p53 and therefore study the proliferative potential of malignant cells; Bcl-2 and Ki-67 were used to assess apoptosis and the degree of malignancy, respectively. The extract enhanced the proliferation of canine osteosarcoma cells, reaching 3,819.74% at 50 µM of curcumin. The extract also significantly altered the expression of mutated p53 and Ki-67 proteins but not that of Bcl-2, suggesting that it did not induce this antiapoptotic pathway. Overall, these results are prerequisite to better understanding how natural compounds such as turmeric ethanolic extract affect cell proliferation and could be used to treat various diseases.

A Curcuma longa L., planta conhecida popularmente como açafrão, tem sido amplamente estudada por suas diversas propriedades terapêuticas, incluindo a ação antineoplásica. O extrato etanólico da planta contém diversos compostos fenólicos, com destaque para a curcumina. O osteossarcoma é um tumor ósseo predominante em cães e humanos, caracterizado por apresentar alto potencial metastático e prognóstico desfavorável. Procurou-se investigar os efeitos de diferentes concentrações de curcumina do extrato etanólico de açafrão sobre células de osteossarcoma canino de cultura estabelecida. As células foram cultivadas e submetidas ao tratamento com extrato com diferentes concentrações de curcumina (0, 10 µM, 20 µM, 50 µM, 100 µM e 1000 µM) e tempos de exposição (24h, 48h e 72h) pelo EEA. Inicialmente, foram realizados: técnica de redução do tetrazólio (MTT) e cálculo da IC50. Posteriormente, após o tratamento com o extrato, realizou-se o ensaio de imunocitoquímica para verificar a expressão de p53 mutada e estudar o potencial proliferativo das células malignas; Bcl-2, com intuito de averiguar o estímulo de via antiapoptótica; e o marcador Ki-67, que sinaliza aumento no grau de malignidade. O extrato promoveu proliferação de células de osteossarcoma canino, com incremento de até 3819,74% na concentração de 50µM de curcumina. O composto também alterou a expressão das proteínas p53 mutante e Ki-67 significativamente, mas não alterou a expressão de Bcl-2, mostrando que não induziu a via antiapoptótica mediada por esta. Estes resultados demonstram que o extrato etanólico do açafrão apresenta potencial proliferativo sobre células de osteossarcoma canino, sugerindo a necessidade de conscientização e conhecimento dos reais efeitos de determinados compostos naturais, considerados seguros ao serem utilizados como tratamento de diversas enfermidades.

Plasmocitoma extramedular oral em felino doméstico / Oral extramedullary plasmocytoma in domestic cat

Plasmocitomas são geralmente incomuns em cães, representando cerca de 3% das neoplasias, e, em gatos, esse número é ainda menor, sendo consideradas raras e observadas em aproximadamente 1% dos casos. Objetiva-se com este trabalho apresentar um relato de caso de uma doença muito pouco relatada na oncologia veterinária, o plasmocitoma extramedular oral em felinos domésticos. A metodologia empregada para a construção deste trabalho deu-se por meio de: consulta a referências bibliográficas; observação e acompanhamento dos processos realizados no âmbito hospitalar, além da consulta ao prontuário médico do paciente. Embora muito descrita na literatura a utilização da cirurgia de mandibulectomia ou maxilectomia na terapia de plasmocitomas orais em cães, são escassos os relatos do emprego da técnica em gatos. Porém, é certo afirmar que a eletroquimioterapia, associada à quimioterapia antineoplásica adjuvante, promoveu uma ótima sobrevida (407 dias), sem comprometimento na qualidade de vida do paciente, mostrando que, mesmo com um tratamento menos invasivo e conservador, foi possível cuidar do paciente de maneira efetiva. Uma grande dificuldade, durante todo o processo, foi a falta de relatos científicos específicos para o plasmocitoma oral em felinos. As neoplasias orais em felinos e, principalmente, as originadas por plasmócitos precisam ser mais estudadas e relatadas, promovendo maior conhecimento técnico e científico a todos os profissionais da área.

Plasmocytomas are generally uncommon in dogs, representing about 3% of neoplasms, and in cats, this number is even lower, being considered rare and observed in approximately 1% of cases. The aim of this work is to present a case report of a disease that is rarely reported in veterinary oncology: oral extramedullary plasmacytoma in domestic cats. The methodology used for the construction of this work was given through: consultation of bibliographic references; observation and monitoring of processes performed in the hospital, in addition to consulting the patient's medical record. Although the use of mandibulectomy or maxillectomy surgery to treat oral plasmacytomas in dogs is widely described in the literature, there are few reports on the use of the technique in cats. However, it is true to say that electrochemotherapy, associated with adjuvant antineoplastic chemotherapy, promoted an excellent survival (407 days), without compromising the patient's quality of life, showing that even with a less invasive and conservative treatment it was possible to care for the patient in a way effective. A major difficulty throughout the process was the lack of specific scientific reports for oral plasmacytoma in felines. Oral neoplasms in felines and mainly those originating from plasmocytes need to be further studied and reported, promoting greater technical and scientific knowledge to all professionals in the field.

Anti-inflammatory activities of arthropod peptides: a systematic review

Peptides obtained from different animal species have gained importance recently due to research that aims to develop biopharmaceuticals with therapeutic potential. In this sense, arthropod venoms have drawn attention, not only because of their toxicity but mainly for the search for molecules with various bioactivities, including anti-inflammatory activity. The purpose of the present study is to gather data available in the literature on new peptides derived from arthropod species with anti-inflammatory potential. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies on peptides from arthropods that display anti-inflammatory activity were retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases. The bibliographic research started in 2020 and searched papers without a limit on the publication date. The articles were analyzed using a search string containing the following terms: "Peptides" and "Anti-inflammatory", in combinations such as "Ant", "Bee", "Wasp", "Crab", "Shrimp", "Scorpion", "Spider", "Tick" and "Centipedes". Besides, a search was carried out in the databases with the terms: "Peptides", "Antitumor", or "Anticancer", and "Arthropods". Articles that met the inclusion and exclusion criteria totalized 171, and these served for data extraction. Additionally, the present review included anti-inflammatory peptides with anticancer properties. Peptides with confirmed anti-inflammatory activity were from insects (ants, bees, and wasps), crustaceans (shrimp and crabs), arachnids (scorpions, spiders, and ticks), and centipedes. These arthropod peptides act mainly by decreasing pro-inflammatory cytokines as analyzed in vitro and in vivo. Some showed significant antineoplastic activity, working in essential cellular pathways against malignant neoplasms.(AU)

Anti-inflammatory activities of arthropod peptides: a systematic review

Peptides obtained from different animal species have gained importance recently due to research that aims to develop biopharmaceuticals with therapeutic potential. In this sense, arthropod venoms have drawn attention, not only because of their toxicity but mainly for the search for molecules with various bioactivities, including anti-inflammatory activity. The purpose of the present study is to gather data available in the literature on new peptides derived from arthropod species with anti-inflammatory potential. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies on peptides from arthropods that display anti-inflammatory activity were retrieved from PubMed, Scopus, Web of Science, and Google Scholar databases. The bibliographic research started in 2020 and searched papers without a limit on the publication date. The articles were analyzed using a search string containing the following terms: "Peptides" and "Anti-inflammatory", in combinations such as "Ant", "Bee", "Wasp", "Crab", "Shrimp", "Scorpion", "Spider", "Tick" and "Centipedes". Besides, a search was carried out in the databases with the terms: "Peptides", "Antitumor", or "Anticancer", and "Arthropods". Articles that met the inclusion and exclusion criteria totalized 171, and these served for data extraction. Additionally, the present review included anti-inflammatory peptides with anticancer properties. Peptides with confirmed anti-inflammatory activity were from insects (ants, bees, and wasps), crustaceans (shrimp and crabs), arachnids (scorpions, spiders, and ticks), and centipedes. These arthropod peptides act mainly by decreasing pro-inflammatory cytokines as analyzed in vitro and in vivo. Some showed significant antineoplastic activity, working in essential cellular pathways against malignant neoplasms.(AU)

Cytotoxic and anticancer properties of the Malaysian mangrove pit viper (Trimeresurus purpureomaculatus) venom and its disintegrin (purpureomaculin)

The Asiatic pit vipers from the Trimeresurus complex are medically important venomous snakes. These pit vipers are often associated with snakebite that leads to fatal coagulopathy and tissue necrosis. The cytotoxic venoms of Trimeresurus spp.; however, hold great potential for the development of peptide-based anticancer drugs. Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue. Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study. Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.(AU)

Anticancer potential of nanogold conjugated toxin GNP-NN-32 from Naja naja venom

Background: Cancer is the second most common fatal disease in the world, behind cardiovascular disorders in the first place. It accounts for around 0.3 million deaths per year in India due to the lack of proper diagnostic facilities, prevention and treatment. Current therapeutic methods do not provide adequate protection and affect normal cells along with cancerous ones. Thus, there is a need for some alternative therapeutic strategy, preferably from natural products, which have been traditionally used for treatment of various diseases in the country. Methods: In this study, we have conjugated purified NN-32 toxin from Naja naja venom with gold nanoparticles and its anticancer potential was evaluated against human breast cancer cell lines. UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy and zeta potential analysis were the techniques used for characterization of GNP-NN-32. Results: GNP-NN-32 showed dose- and time-dependent cytotoxicity against breast cancer cell lines (MCF-7 and MDA-MB-231). NN-32 and GNP-NN-32 induced apoptosis in both breast cancer cell lines. The results of CFSE cell proliferation study revealed that NN-32 and GNP-NN-32 arrested cell division in both MCF-7 and MDA-MB-231 cell lines resulting in inhibition of proliferation of these cancer cells. Conclusion: GNP-NN-32 showed an anticancer potential against human breast cancer cell lines. Analysis of detailed chemical characterization along with its cytotoxic property might help to perceive a new dimension of the anti-cancer potential of GNP-NN-32 that will enhance its biomedical function in near future.(AU)

Aspectos clínicos, laboratoriais e tratamento da leucemia mieloide crônica em cão: relato de caso / Clinical aspects, hematological changes and treatments of chronic myeloid leukemia in dog: case report

O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias após ao início do tratamento com hidroxiureia.

The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient's anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.