Síntesis de evidencia. Cianobacterias, efectos a la salud humana, animal y ambiental / Synthesis of evidence. Cyanobacteria, effects on human, animal and environmental health

Los cuerpos de agua dulce albergan una gran cantidad de microorganismos cruciales para los ecosistemas acuáticos, incluyendo las cianobacterias. Sin embargo, su proliferación descontrolada representa riesgos para la salud humana, animal y el medio ambiente. Esta revisión destaca los efectos adversos de las cianobacterias y sus toxinas, así como los métodos de detección y prevención. La gestión efectiva de estos eventos requiere una comprensión integral de los factores ambientales y un enfoque preventivo en el tratamiento del agua. Se necesitan estrategias multifacéticas que incluyan la monitorización continua, medidas de tratamiento adecuadas y políticas de conservación ambiental para abordar este desafío

Freshwater bodies host a large number of microorganisms crucial to aquatic ecosystems, including cyanobacteria. However, their uncontrolled proliferation poses risks to human, animal and environmental health. This review highlights the adverse effects of cyanobacteria and their toxins, as well as detection and prevention methods. Effective management of these events requires a comprehensive understanding of environmental factors and a preventive approach to water treatment. Multifaceted strategies including continuous monitoring, appropriate treatment measures and environmental conservation policies are needed to address this challenge

Animais que curam: um olhar da família e terapeuta / Animals that heal: a family and therapist perspective

Conhecer e compreender as contribuições da Terapia Assistida por Animais no desenvolvimento do indivíduo e no restabelecimento da saúde, na concepção dos cuidadores e familiares. Método: pesquisa descritiva exploratória, com abordagem qualitativa, em uma empresa privada de Intervenções Assistidas com Animais da região noroeste do Estado do Rio Grande do Sul, no segundo semestre de 2022. Os participantes foram os familiares e/ou cuidadores dos praticantes e a terapeuta. A coleta de dados deu-se por meio de questionário semiestruturado e a análise dos dados através da análise de conteúdo das falas e aprovada pelo parecer nº 5.652.286. Resultados: Verifica-se que os benefícios no desenvolvimento estão associados a aspectos como melhora no fortalecimento do tônus muscular, na linguagem, na autonomia, na coordenação motora, na tranquilidade e na afetividade. Conclusão: Essa intervenção tem grande potencial dentro do tratamento dos praticantes, e merece ser cada vez mais estudada.(AU)

To know and understand the contributions of Animal Assisted Therapy in the development of the individual and the restoration of health, in the conception of caregivers and family members. Method: exploratory descriptive research, with a qualitative approach, in a private Animal Assisted Interventions company in the northwest region of the State of Rio Grande do Sul, in the second half of 2022. The participants were the family members and/or caregivers of the practitioners and the therapist . Data collection took place through a semi-structured questionnaire and data analysis through content analysis of the statements and approved by opinion no. 5,652,286. Results: It appears that the benefits in development are associated with aspects such as improvements in strengthening muscle tone, language, autonomy, motor coordination, tranquility and affectivity. Conclusion: This intervention has great potential in the treatment of practitioners, and deserves to be increasingly studied.(AU)

Conocer y comprender los aportes de la Terapia Asistida con Animales en el desarrollo del individuo y el restablecimiento de la salud, en la concepción de los cuidadores y familiares. Método: investigación descriptiva exploratoria, con enfoque cualitativo, en una empresa privada de Intervenciones Asistidas con Animales en la región noroeste del Estado de Rio Grande do Sul, en el segundo semestre de 2022. Los participantes fueron los familiares y/o cuidadores de los practicantes y el terapeuta. La recolección de datos se realizó a través de un cuestionario semiestructurado y el análisis de los datos mediante análisis de contenido de los enunciados aprobados por dictamen nº 5.652.286. Resultados: Parece que los beneficios en el desarrollo están asociados a aspectos como mejoras en el fortalecimiento del tono muscular, el lenguaje, la autonomía, la coordinación motora, la tranquilidad y la afectividad. Conclusión: Esta intervención tiene un gran potencial en el tratamiento de los profesionales y merece ser cada vez más estudiada

Syagrus flexuosa (Mart.) Becc. (Arecaceae) seedling recruitment at the edge and interior of Cerrado remnants / Recrutamento de plântulas em Syagrus flexuosa (Mart.) Becc. (Arecaceae), na borda e interior de remanescentes de Cerrado

The edge effect has impacts on seed and seedling survival due to modifications in biotic and abiotic factors. Often, large-seeded tree species lost seed vectors in the forest edge due to the rarity or absence of large frugivores at this habitat type. In this study, I compared the seedling abundance and distribution of the palm Syagrus flexuosa between edges and interiors of three large Cerrado remnants. In every remnant, the number of seedlings around parent palms in the edge was smaller than around palm individuals located in the Cerrado interior. Moreover, the distribution of seedlings around parent palms differed between edges and interiors. In the edges, most seedlings were found under parent crowns, while in the interiors, the contrary occurred. The high concentration of seedlings under parent palms suggests a decrease of seed dispersal at the edges. Because S. flexuosa is a widely distributed palm that serves as an important resource for several animals along Cerrado habitats, changes on the regeneration process of this palm due to edge effects can further impact frugivore populations. Therefore, the decline of seedling establishment along forest edges implies changes in the Cerrado regeneration dynamics, which may compromise the persistence of ecological processes and animal communities.

O efeito de borda tem impactos severos na sobrevivência de sementes e plântulas devido a modificações dos fatores bióticos e abióticos. Frequentemente, espécies arbóreas com sementes grandes perdem seus dispersores na borda da floresta devido à raridade ou ausência de grandes frugívoros neste tipo de habitat. Neste estudo, comparei a abundância e distribuição de plântulas de S. flexuosa entre bordas e interiores de três grandes remanescentes de Cerrado. Em cada remanescente, o número de plântulas ao redor das palmeiras-mãe, na borda, era menor do que ao redor dos indivíduos no interior do Cerrado. Nas bordas, a maioria das plântulas foi encontrada junto às plantas mãe, enquanto no interior ocorreu o contrário. A alta concentração de plântulas sob as plantas adultas sugere diminuição da dispersão de sementes nas bordas. Como S. flexuosa é uma palmeira amplamente distribuída que serve como um recurso importante para vários animais nos habitats do Cerrado, mudanças no processo de regeneração dessa palmeira devido aos efeitos de borda podem impactar ainda mais as populações de frugívoros. Portanto, o declínio do estabelecimento de plântulas ao longo das bordas do Cerrado implica em mudanças na dinâmica de regeneração do Cerrado, o que pode comprometer a persistência de processos ecológicos e comunidades animais.

Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor / 中国结合医学杂志

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

The Uptake and Distribution Evidence of Nano- and Microplastics in vivo after a Single High Dose of Oral Exposure / 生物医学与环境科学（英文）

OBJECTIVE@#Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.@*METHODS@#Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg∙body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.@*RESULTS@#In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group ( P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h ( P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h ( P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.@*CONCLUSION@#Nanoplastics translocated rapidly to observed organs/tissues through blood circulation; however, only small amounts of MPs could penetrate the organs.

Effect of glutaminase 1 inhibitor on carbon tetrachloride-induced liver fibrosis in mice / 中国生物制品学杂志

@#Objective To investigate the effect of glutaminase 1(GLS1)specific inhibitor BPTES[bis-2-（5-phenylacetamido-1,3,4-thiadiazol-2-yl）ethyl sulfide]on the liver fibrosis in the mouse model of liver fibrosis induced by carbon tetrachloride(CCl4).Methods Male C57BL/6J mice were intraperitoneally injected with olive oil(control group),10%CCl4(10 μL/g,model group)or 10% CCl4(10 μL/g)+ BPTES(10 mg/kg,treatment group),with 10 mice in each group,two doses a week for four weeks to establish liver fibrosis model. Collagen deposition in mouse liver tissue was observed by Sirius red staining. The expression levels of actin alpha 2(Acta2),collagen typeⅠalpha 1(Col1a1)GLS1 and GLS1 protein were detected by qRT-PCR and immunohistochemical staining.Results Compared with the control group,the liver tissue of mice in the model group was generally enlarged,the surface was not smooth and granular,and the ratio of liver mass to tibia length significantly increased(t = 2. 979,P < 0. 05);The Sirius red positive area of collagen deposition increased signifi-cantly in the liver tissue of mice in the model group(t = 7. 661,P < 0. 01),the relative expression levels of Acta2 and Col1a1 significantly increased(t = 4. 335 and 5. 319,respectively,each P < 0. 01),and the mRNA and protein levels of GLS1 significantly increased(t = 5. 319 and 9. 725,respectively,each P < 0. 01). However,compared with the model group,the BPTES treatment group had a reduction in liver mass,a significant reduction in the Sirius red positive area of collagen deposition in liver tissue(t = 7. 427,P < 0. 01),and a significant reduction in the relative expressions of Atca2 and Col1a1(t = 3. 713 and 2. 628,respectively,each P < 0. 05).Conclusion Inhibition of GLS1activity can significantly improve the degree of liver fibrosis induced by CCl4,providing a new idea for the treatment of liver fibrosis.

Fitting Degrees of Animal Models of Diarrhea-irritable Bowel Syndrome with Clinical Characteristics of Western Medicine and Traditional Chinese Medicine / 中国实验方剂学杂志

Diarrhea-irritable bowel syndrome （IBS-D） is one of the common functional bowel diseases in clinical practice. Since it pathogenesis is complex and has not been fully elucidated， effective treatment methods remains to be developed for this disease. Establishing the animal models of IBS-D in accordance with the clinical characteristics of traditional Chinese medicine （TCM） and Western medicine helps to reveal the pathogenesis of this disease and improve the treatment plan. The fitting degree of an animal model with clinical characteristics is an indicator to evaluate the effectiveness of the animal model in simulating the disease characteristics of Western medicine and the syndromes of TCM based on the latest diagnostic standards. By reviewing the relevant articles about the animal models of IBS-D， we discovered that rats were the preferred animals for modeling， and the models were mainly induced by single factors， double factors， or the combination of multiple factors. The established animal models mainly present symptoms or signs associated with visceral hypersensitivity or/and gastrointestinal motility abnormalities. The single factor-induced rat models of IBS-D had high fitting degrees with the clinical characteristics of Western medicine but low fitting degrees with the TCM syndromes. The animal models induced by two or more factors had high but varied fitting degrees with the clinical characteristics of Western medicine. In addition， the animal models of IBS-D considering TCM syndromes mainly focuses on the syndrome of liver depression and spleen deficiency， and few models were established for the syndromes of spleen-kidney Yang deficiency， spleen-stomach dampness-heat， spleen deficiency and dampness excess， and cold and heat in complexity. Therefore， it is essential to improve the existing or develop new animal models of IBS-D in the future， so as to provide more tools for deciphering the mechanisms of TCM and Western medicine and developing treatment methods for this disease.

Current research status of animal models for acute-on-chronic liver failure / 临床肝胆病杂志

Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models.

Establishment and application of animal models for portal vein thrombosis / 临床肝胆病杂志

Portal vein thrombosis （PVT） refers to thromboembolism that occurs in the extrahepatic main portal vein and/or intrahepatic portal vein branches. PVT is the result of the combined effect of multiple factors， but its pathogenesis remains unclear. Animal models are an important method for exploring the pathophysiological mechanism of PVT. Based on the different species of animals， this article reviews the existing animal models of PVT in terms of modeling methods， principles， advantages and disadvantages， and application.

Establishment and Evaluation of Animal Model of Acute Myocardial Infarction with Syndrome of Qi and Yin Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the establishment and evaluation methods of the rat model of acute myocardial infarction （AMI） in coronary heart disease with the syndrome of Qi and Yin deficiency by sleep deprivation （SD） combined with isoproterenol （ISO） and preliminarily explore its biological basis. MethodForty SD rats were assigned into normal （no treatment）， SD （treatment in modified multi-platform water environment for 96 h）， ISO （subcutaneous injection of ISO at 100 mg·kg-1 once every other day for a total of 2 times）， and SD+ISO （injection of 100 mg·kg-1 ISO after SD for 72 h and 96 h） groups. The cardiac function was detected by small animal echocardiography. The serum levels of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， and cardiac troponin T （cTnT） were measured by biochemical methods. The pathological changes of the myocardial tissue were observed by hematoxylin-eosin staining. The general state， body weight， grip strength， body temperature， behaviors in open field test， serum levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， cAMP/cGMP ratio， red （R）， green （G）， blue （B） values of the tongue surface， and pulse amplitude were observed and measured to evaluate the modeling results. Enzyme-linked immunosorbent assay was employed to determine the serum levels of interleukin-18 （IL-18）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， malondialdehyde （MDA）， corticotropin-releasing factor （CRF）， adrenocorticotropic hormone （ACTH）， triiodothyronine （T3）， tetraiodothyronine （T4）， cluster of differentiation 4 （CD4）， and cluster of differentiation 8 （CD8）. ResultIn terms of disease indicators， the ISO and SD+ISO groups had lower cardiac function indicators than the normal group （P<0.01）. The levels of CK， CM-MB， LDH and cTnT elevated in each model group compared with the normal group （P<0.01）. The pathological changes of myocardial tissue were obvious in the ISO and SD+ISO groups. In terms of syndrome indicators， compared with the normal group， the SD and SD+ISO groups showed decreased body weight at each time point （P<0.01）， and the ISO group showed decreased body weight at the time points of 48 h and 72 h （P<0.05， P<0.01）. The paw temperature and rectal temperature increased in the SD group （P<0.01）. The model groups showed weakened grasp strength， lowered R， G， and B values of the tongue surface （P<0.01）， prolonged immobility time （P<0.01）， reduced total distance and number of entering the central area （P<0.01）， decreased average speed （P<0.05， P<0.01）， and increased cAMP and cGMP （P<0.05， P<0.01）. The cAMP/cGMP ratio was increased in the SD+ISO group （P<0.01）， and the pulse amplitude was decreased in the SD and SD+ISO groups （P<0.01）. In terms of serological indicators，compared with the normal group， the levels of IL-18， TNF-α， SOD and MDA were significantly increased in the ISO and SD+ISO groups （P<0.01）， the CRF， ACTH， CORT， T3， T4， CD4 and CD8 in the model groups were increased （P<0.05， P<0.01）. ConclusionSleep deprivation for 96 h combined with high-dose ISO can successfully establish a rat model of acute myocardial infarction in coronary heart disease with the syndrome of Qi and Yin deficiency. The model evaluation system can be built with disease indicators of western medicine， histopathological indicators， macroscopic indicators of traditional Chinese medicine， and serological indicators.

Mechanism of Ruanmai decoction in treating atherosclerosis based on YWHAZ/p38MAPK/CASP3 signaling pathway / 中国药理学通报

Aim To explore the mechanism of action of Ruanmai decoction in treating atherosclerosis through network pharmacology. Methods The chemical components and targets of Ruanmai decoction were queried using TCMSP. Relevant targets for atherosclerosis were retrieved from DrugBank, GeneCards, OMIM, and TTD databases. The " Drug-Active Ingredient-Target" PPI network was constructed using Cyto-scape software. GO and KEGG enrichment analysis were performed using the David database. Molecular docking verification of key components with core targets was conducted using the Seesar software. Atherosclerosis mouse models were established by feeding ApoE mice with a high-fat diet, and Ruanmai decoction granules were administered orally. Aortic pathological sections were stained, blood lipids were measured, and immunofluorescence was used to detect Mac2 and YWHAZ protein expression. Western blot was used to detect p-p38MAPK and C-CASP3 protein expression. Results Ruanmai decoction screened a total of 72 active drug components corresponding to 168 target genes for the treatment of atherosclerosis. The targets were primarily enriched in biological processes related to lip-id metabolism, inflammation and immunity, oxidative stress, vascular endothelial function, cell proliferation and apoptosis, glycolysis, and ubiquitination. Signaling pathways such as МАРК, TNF, PDK-Akt, and IL-17 were also involved. Animal experiments verified that RMJ could regulate the p38MAPK signaling pathway by down-regulating key targets YWHAZ, p-p38MAPK, and C-CASP3, thereby reducing AS inflammation and inflammation-induced apoptosis. Conclusions Ruanmai decoction can inhibit the expression of YWHAZ and activate the p38MAPK signaling pathway, potentially improving vascular inflammation, lipid metabolism, oxidative stress, and other pathological processes by regulating the МАРК, TNF, PDK-Akt, and IL-17 signaling pathways, thus preventing and treating atherosclerosis.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Research progress on bone metabolism and molecular mechanisms in accelerated aging SAMP6 mice / 中国药理学通报

Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. The pathogenesis of SOP is complex and not well understood. Currently, the rapid aging model mouse, senescence accelerated mouse prone 6 (SAMP6), is an ideal model for studying the mechanisms of SOP development and exploring its prevention and treatment. This model exhibits characteristics including increased bone fragility, degradation of bone microstructure, loss of bone matrix, and abnormal metabolism and dysfunction of bone cells, faithfully replicating the process of SOP occurrence and progression at both macroscopic and microscopic levels.

Application of Animal Models of Corneal Neovascularization Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo provide a reference for the establishment of an ideal corneal neovascularization （CNV） animal model by summarizing the modeling characteristics of CNV animal models. MethodWith "CVN" as the theme word， this paper searched the China National Knowledge Infrastructure （CNKI）， Wanfang， Chinese medical journals full-text database， and PubMed database and screened out relevant literature on CNV animal experiments from 2013 to 2023. The database was established by Excel 2021， and the experimental animal strain， gender， modeling method， detection index， and application category were sorted out. The characteristics of the CNV animal model were analyzed. ResultAfter comparative analysis， it was found that the animal strains were Sprague-Dawley rats （87 times， 29.49%） and New Zealand white rabbits （52 times， 17.63%）. Male animals were recommended. Most modeling methods for efficacy verification and mechanism studies were the alkali burn method. Index detection methods included apparent index observation， histopathological detection， immunohistochemistry （IHC）， Western blot， and various polymerase chain reaction （PCR） tests. Detection indexes included apparent indication， corneal histopathology， CNV regulation， etc. ConclusionThe CNV model of SD rats induced by the alkali burn method is recommended for model replication， and the indexes are mainly selected from the growth of CNV， corneal histopathological test， and vascular endothelial growth factor （VEGF）-related test. In addition， according to the demand， the corneal apparent indication and the basic indexes related to the regulation of CNV， such as vascular endothelial growth factor receptor 2 （VEGFR2）， basic fibroblast growth factor （bFGF）， and secretogranin Ⅲ （Scg3） are also selected. Clinical treatment of CNV relies on anti-inflammatory drugs and anti-VEGF drugs， and there is a lack of application of traditional Chinese medicine （TCM）， so the model needs to be improved by adding elements of TCM syndromes.

Animal Models of Ovarian Cancer Based on Characteristics of Clinical Symptoms of Traditional Chinese and Western Medicine / 中国实验方剂学杂志

ObjectiveOvarian cancer is the third most common gynecologic cancer worldwide， with the second highest mortality rate among gynecologic cancers， and age-standardized rates are gradually increasing in many low- and middle-income countries. At present， its etiology and pathogenesis are not clear. There are no obvious symptoms in the early stage， and when the symptoms become obvious， it often indicates the advanced stage. The 5-year survival rate of the advanced stage is only 17%， which poses a great threat to women's health. Therefore， an in-depth study of the etiology and pathogenesis of ovarian cancer is very important to the exploration of prevention and treatment methods for ovarian cancer. Based on the clinical characteristics of ovarian cancer in traditional Chinese and Western medicine， and combined with the existing evaluation methods of animal models， this study evaluated the animal model of ovarian cancer， and provided analysis and suggestions. MethodThis study searched China National Knowledge Infrastructure （CNKI）， Wanfang data， VIP information database， and PubMed database using the keywords "ovarian cancer" and "animal model"， excluded the articles that did not meet the criteria， and then classified the remaining studies. Combined with the clinical diagnostic criteria of Western medicine and traditional Chinese medicine syndrome differentiation， the related indicators of ovarian cancer animal models were assigned and the degree of agreement was evaluated. ResultThe use of the transplanted animal model exhibited the highest frequency， followed by that of the induced model. The degree of agreement of traditional Chinese medicine for each model was lower than that of Western medicine. The induced ovarian cancer model had a high degree of clinical agreement and was similar to human ovarian cancer in terms of tumor growth pattern， disease progression and complications， which is an ideal animal model of ovarian cancer. Although this animal model can simulate the etiology and pathogenesis of ovarian cancer to a certain extent and reflect some indicators of traditional Chinese and Western medicine， it lacks differentiation of traditional Chinese medicine syndromes. ConclusionOn the basis of the original model， the animal model of ovarian cancer was added with Qi deficiency syndrome， blood deficiency syndrome， Qi stagnation syndrome， blood stasis syndrome， heat-toxin syndrome， and Yang deficiency syndrome to establish an animal model combining traditional Chinese medicine disease and syndrome of ovarian cancer， which could better simulate the clinical actual situation of traditional Chinese and Western medicine and lay a solid foundation for the study of integrated traditional Chinese and Western medicine for the treatment of ovarian cancer.

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Physiological responses of tambaqui (Colossoma macropomum) fed diets supplemented with silage from fish and vegetables residues

Abstract The demand for products to replace high-cost raw materials, such oil and fish meal, in the manufacture of feed for use in aquaculture, while also guaranteeing the nutritional quality of the diets, is increasing. Silage produced with fish and vegetables residues is a low-cost and efficient protein source. The objective of the present study was to evaluate the physiological and biochemical responses of tambaqui fingerlings fed four different levels of silage included in commercial feed with 28% crude protein, over two periods: 45 and 90 days. Each treatment was carried out over three replications, with 10 tambaqui in each 100 L experimental tank. At the end of each established period, blood samples were collected from five animals from each repetition to determine the hematological and biochemical variables. Body weight and total length, hepatosomatic and liposomal indices and hematocrit of specimens fed with diets supplemented with silage did not exhibit significant changes in both assessment period. After 45 days of feeding, the hemoglobin concentration increased when tambaqui were fed a diet including 20% silage. The red blood cell count, mean corpuscular volume and mean corpuscular hemoglobin did not change between treatments in either period. The total protein concentrations increased significantly in the plasma of tambaqui fed with diets with the inclusion of 5 and 10% of silage, evaluated after feeding for 45 days. It was found that the groups which had silage included in their diet did not exhibit significant alterations in the evaluated parameters, and the diet was therefore not consider harmful to the health of tambaqui. Therefore, the use of silage as a feed supplement during tambaqui farming is a sustainable alternative for producers, as it leads to a reduction of impacts of fish and vegetables waste disposal.

Resumo A procura por insumos que substituam produtos de alto custo, como óleo e farinha de peixe, na fabricação de rações para uso na aquicultura é crescente, sendo necessário garantir a qualidade nutricional das dietas. A silagem produzida a partir de resíduos de pescado e de vegetais apresenta-se como uma alternativa de baixo custo e eficiente fonte proteica. O objetivo do presente estudo foi avaliar as respostas fisiológicas e bioquímicas de alevinos de tambaqui alimentados com quatro níveis de inclusão de silagem em ração comercial com 28% de proteína bruta, em dois períodos: 45 e 90 dias. Cada tratamento foi realizado em três repetições, com 10 tambaquis em cada caixa experimental de 100 L. Ao término de cada período estabelecido, amostras sanguíneas foram coletadas de cinco animais de cada repetição para determinação das variáveis hematológicas e bioquímicas. Peso, comprimento total e índices hepatossomático e lipossomático de espécimes alimentados com silagem não mostraram alterações significativas em ambos os períodos de avaliação, bem como os valores de hematócrito. A concentração de hemoglobina de tambaqui após 45 dias de alimentação aumentou quando foi fornecida dieta com inclusão de 20% de silagem. A contagem de eritrócitos, volume corpuscular médio e hemoglobina corpuscular média não apresentaram alterações entre os tratamentos, em ambos os períodos. As proteínas totais aumentaram significativamente no plasma de tambaquis que receberam dietas com inclusão de 5 e 10% de silagem, avaliados após 45 dias de alimentação. Evidenciou-se que os grupos com inclusão de silagem na dieta não apresentaram alterações significativas nos parâmetros avaliados, assim não sendo prejudiciais à higidez do tambaqui. Portanto, o uso da silagem como suplemento alimentar durante o cultivo do tambaqui é uma alternativa sustentável para produtores, por promover a redução do descarte de resíduos de pescado e da agricultura.

Syagrus flexuosa (Mart.) Becc. (Arecaceae) seedling recruitment at the edge and interior of Cerrado remnants

Abstract The edge effect has impacts on seed and seedling survival due to modifications in biotic and abiotic factors. Often, large-seeded tree species lost seed vectors in the forest edge due to the rarity or absence of large frugivores at this habitat type. In this study, I compared the seedling abundance and distribution of the palm Syagrus flexuosa between edges and interiors of three large Cerrado remnants. In every remnant, the number of seedlings around parent palms in the edge was smaller than around palm individuals located in the Cerrado interior. Moreover, the distribution of seedlings around parent palms differed between edges and interiors. In the edges, most seedlings were found under parent crowns, while in the interiors, the contrary occurred. The high concentration of seedlings under parent palms suggests a decrease of seed dispersal at the edges. Because S. flexuosa is a widely distributed palm that serves as an important resource for several animals along Cerrado habitats, changes on the regeneration process of this palm due to edge effects can further impact frugivore populations. Therefore, the decline of seedling establishment along forest edges implies changes in the Cerrado regeneration dynamics, which may compromise the persistence of ecological processes and animal communities.

Resumo O efeito de borda tem impactos severos na sobrevivência de sementes e plântulas devido a modificações dos fatores bióticos e abióticos. Frequentemente, espécies arbóreas com sementes grandes perdem seus dispersores na borda da floresta devido à raridade ou ausência de grandes frugívoros neste tipo de habitat. Neste estudo, comparei a abundância e distribuição de plântulas de S. flexuosa entre bordas e interiores de três grandes remanescentes de Cerrado. Em cada remanescente, o número de plântulas ao redor das palmeiras-mãe, na borda, era menor do que ao redor dos indivíduos no interior do Cerrado. Nas bordas, a maioria das plântulas foi encontrada junto às plantas mãe, enquanto no interior ocorreu o contrário. A alta concentração de plântulas sob as plantas adultas sugere diminuição da dispersão de sementes nas bordas. Como S. flexuosa é uma palmeira amplamente distribuída que serve como um recurso importante para vários animais nos habitats do Cerrado, mudanças no processo de regeneração dessa palmeira devido aos efeitos de borda podem impactar ainda mais as populações de frugívoros. Portanto, o declínio do estabelecimento de plântulas ao longo das bordas do Cerrado implica em mudanças na dinâmica de regeneração do Cerrado, o que pode comprometer a persistência de processos ecológicos e comunidades animais.

Advances and challenges in animal source food inspection legislation for Brazilian small-scale and artisanal producers / Avanços e desafios na legislação de inspeção de alimentos de origem animal para pequenos produtores e produtores artesanais no Brasil / Avances y desafíos en la legislación de inspección de alimentos de origen animal para pequeños productores y productores artesanos brasileños

Abstract: The strict sanitary inspection legislation of animal source food has been considered a trade barrier for smallholder farmers and small-scale producers in Brazil. In this sense, law flexibilization is suggested to facilitate national trade of these products. We conducted a social and sanitary analysis, presenting the current Brazilian conjuncture and difficulties for animal source food Brazilian inspection law flexibilization. By discussing inequalities, human rights issues, animal source food legislation, and international food safety standards, we evidenced critical barriers for legislative reform in Brazil. Among these barriers, the main ones are social inequalities; high zoonotic risk of animal source food products; the Brazilian political structure and its reflection on different inspection practices among country jurisdictions; and the lack of inspection services in most Brazilian municipalities. At the same time, we present positive updates in the normative framework, and point out game-changers to modify the actual safety and trade situations of Brazilian small-scale and artisanal animal source food products, including policies to strengthen state and municipal inspection services and harmonization initiatives based on international standards and national legislation. We also suggest policies to implement inspection services in municipalities, whether by municipal action or by a consortium, as well as policies to strengthen technical assistance and rural extension for small-scale and artisanal producers. These policies aim to reduce technical and sanitary education inequalities and build a fairer animal source food system.

Resumo: A rigorosa legislação de inspeção sanitária de alimentos de origem animal tem sido considerada uma barreira comercial para agricultores familiares e pequenos produtores no Brasil. Nesse sentido, sugestiona-se a flexibilização das leis para facilitar o comércio nacional destes produtos. Realizamos uma análise sociosanitária, apresentando a atual conjuntura brasileira e apontando as dificuldades para a flexibilização da lei de inspeção de alimentos de origem animal. Discutindo as desigualdades brasileiras, os direitos humanos, a legislação brasileira sobre alimentos de origem animal e as normas internacionais de segurança de alimentos, evidenciamos pontos críticos que constituem o desafio para a reforma da legislação, sendo eles: desigualdades sociais; alto risco zoonótico de produtos de origem animal; a estrutura política brasileira e seu reflexo nas diferentes práticas de fiscalização entre as jurisdições do país; e a falta de inspeção oficial na maioria dos municípios brasileiros. Ao mesmo tempo, apresentamos atualizações positivas no arcabouço normativo e apontamos divisores de águas para modificar a real situação de segurança e comércio dos produtos de origem animal brasileiros de pequena escala e artesanais, incluindo políticas relacionadas ao fortalecimento dos serviços de inspeção estaduais e municipais e iniciativas de harmonização com base em padrões internacionais e legislação nacional; políticas de implantação dos serviços de inspeção oficial nos municípios, seja por ação municipal ou por consórcio; e políticas de fortalecimento da assistência técnica e extensão rural para pequenos produtores e produtores artesanais, em prol da redução das desigualdades na educação técnica e sanitária e construção de um sistema alimentar de origem animal mais justo.

Resumen: La estricta legislación de inspección sanitaria de alimentos de origen animal ha sido considerada una barrera comercial para los agricultores familiares y pequeños productores en Brasil. En ese sentido, se sugiere flexibilizar la ley para facilitar el comercio nacional de estos productos. Realizamos un análisis sociosanitario, presentando la coyuntura actual brasileña y señalando las dificultades para flexibilizar la ley de Inspección de alimentos de origen animal. Al discutir las desigualdades brasileñas, los derechos humanos, la legislación brasileña sobre alimentos de origen animal y las normas internacionales de seguridad alimentaria, destacamos puntos críticos que constituyen el desafío para la reforma de la legislación, a saber: desigualdades sociales; alto riesgo zoonótico de los productos de origen animal; la estructura política brasileña y su reflejo en las diferentes prácticas de inspección entre las jurisdicciones del país; y la falta de inspección oficial en la mayoría de los municipios brasileños. A la vez, presentamos actualizaciones positivas en el marco normativo y señalamos parteaguas para cambiar la situación real de seguridad y comercio de los productos de origen animal brasileños de pequeña escala y artesanía, incluidas políticas relacionadas con el fortalecimiento de los servicios de inspección estatales y municipales e iniciativas de armonización con base en normas internacionales y legislación nacional; políticas para la implementación de servicios oficiales de inspección en los municipios, ya sea por acción municipal o por consorcio; y políticas para fortalecer la asistencia técnica y la extensión rural a pequeños productores y productores artesanos, para reducir las desigualdades en la educación técnica y sanitaria y construir un sistema de alimentos de origen animal más justo.

Physiological responses of tambaqui (Colossoma macropomum) fed diets supplemented with silage from fish and vegetables residues / Respostas fisiológicas de tambaqui (Colossoma macropomum) alimentado com dietas suplementadas com silagem de resíduos de pescado e vegetais

The demand for products to replace high-cost raw materials, such oil and fish meal, in the manufacture of feed for use in aquaculture, while also guaranteeing the nutritional quality of the diets, is increasing. Silage produced with fish and vegetables residues is a low-cost and efficient protein source. The objective of the present study was to evaluate the physiological and biochemical responses of tambaqui fingerlings fed four different levels of silage included in commercial feed with 28% crude protein, over two periods: 45 and 90 days. Each treatment was carried out over three replications, with 10 tambaqui in each 100 L experimental tank. At the end of each established period, blood samples were collected from five animals from each repetition to determine the hematological and biochemical variables. Body weight and total length, hepatosomatic and liposomal indices and hematocrit of specimens fed with diets supplemented with silage did not exhibit significant changes in both assessment period. After 45 days of feeding, the hemoglobin concentration increased when tambaqui were fed a diet including 20% silage. The red blood cell count, mean corpuscular volume and mean corpuscular hemoglobin did not change between treatments in either period. The total protein concentrations increased significantly in the plasma of tambaqui fed with diets with the inclusion of 5 and 10% of silage, evaluated after feeding for 45 days. It was found that the groups which had silage included in their diet did not exhibit significant alterations in the evaluated parameters, and the diet was therefore not consider harmful to the health of tambaqui. Therefore, the use of silage as a feed supplement during tambaqui farming is a sustainable alternative for producers, as it leads to a reduction of impacts of fish and vegetables waste disposal.

A procura por insumos que substituam produtos de alto custo, como óleo e farinha de peixe, na fabricação de rações para uso na aquicultura é crescente, sendo necessário garantir a qualidade nutricional das dietas. A silagem produzida a partir de resíduos de pescado e de vegetais apresenta-se como uma alternativa de baixo custo e eficiente fonte proteica. O objetivo do presente estudo foi avaliar as respostas fisiológicas e bioquímicas de alevinos de tambaqui alimentados com quatro níveis de inclusão de silagem em ração comercial com 28% de proteína bruta, em dois períodos: 45 e 90 dias. Cada tratamento foi realizado em três repetições, com 10 tambaquis em cada caixa experimental de 100 L. Ao término de cada período estabelecido, amostras sanguíneas foram coletadas de cinco animais de cada repetição para determinação das variáveis hematológicas e bioquímicas. Peso, comprimento total e índices hepatossomático e lipossomático de espécimes alimentados com silagem não mostraram alterações significativas em ambos os períodos de avaliação, bem como os valores de hematócrito. A concentração de hemoglobina de tambaqui após 45 dias de alimentação aumentou quando foi fornecida dieta com inclusão de 20% de silagem. A contagem de eritrócitos, volume corpuscular médio e hemoglobina corpuscular média não apresentaram alterações entre os tratamentos, em ambos os períodos. As proteínas totais aumentaram significativamente no plasma de tambaquis que receberam dietas com inclusão de 5 e 10% de silagem, avaliados após 45 dias de alimentação. Evidenciou-se que os grupos com inclusão de silagem na dieta não apresentaram alterações significativas nos parâmetros avaliados, assim não sendo prejudiciais à higidez do tambaqui. Portanto, o uso da silagem como suplemento alimentar durante o cultivo do tambaqui é uma alternativa sustentável para produtores, por promover a redução do descarte de resíduos de pescado e da agricultura.