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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling

Chinese Journal of Integrative Medicine 2024年第6期30卷 525-533页

作者： Lucas dos santos Zamarioli Michele Rosana Maia santos Adolfo Garcia Erustes Vanessa Marques Meccatti Thais cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto Department of Pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research Group on Phytocomplexes and Cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil Department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)*** and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling

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Use of Initial Modified RECIST Tumor Response Evaluation Criteria for Predicting Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization with Drug-Eluting Beads

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Journal of Cancer Therapy 2015年第13期6卷 1115-1123页

作者： Natália Sousa Freitas Queiroz Luciana Kikuchi Regis Otaviano Franca Bezerra Regiane S. S. M. Alencar aline Lopes Chagas Cláudia Megumi Tani Márcio Augusto Diniz aline cristine barbosa santos Airton Mota Moreira Manoel de Souza Rocha Luiz Augusto Carneiro D’Albuquerque Francisco César Carnevale Flair José Carrilho Sao Paulo Clínicas Liver Cancer Group Instituto do Cancer do Estado de Sao Paulo Hospital das Clínicas Department of Gastroenterology University of Sao Paulo School of Medicine Sao Paulo Brazil Sao Paulo Clínicas Liver Cancer Group Instituto do Cancer do Estado de Sao Paulo Hospital das Clínicas Department of Radiology University of Sao Paulo School of Medicine Sao Paulo Brazil

Introduction: Transarterial chemoembolization (TACE) reduces tumor growth and increases survival in patients with hepatocellular carcinoma (HCC). Drug-eluting beads (DEB) deliver slow-release chemotherapy and reduce systemic toxicity during TACE. This study correlated initial tumor response according to modified RECIST (mRECIST) criteria and 1-year survival in patients with HCC treated with TACE-DEB, and identified predictors of tumor response. Methods: Fifty-two patients with HCC received TACE-DEB loaded with doxorubicin 75 mg during a 6-month period. Tumor response was evaluated 1 month after the procedure according to mRECIST criteria. Results: Most patients were cirrhotic and etiology of liver disease was hepatitis C in 26/52 (50%). Similar numbers of patients had Barcelona Clinic Liver Cancer (BCLC) A and BCLC B disease. Most patients had one nodule (66%). Complete response (CR) was achieved in 12/52 (23%), partial response in 19/52 (37%), stable disease in 4/52 (8%) and progressive disease in 17/52 (32%). Largest HCC ≤58 mm and BCLC stage A were associated with CR. The 1-year survival was 74%, with survival rates of 95% and 56% in the BCLC A and B groups, respectively. Variables reflecting tumor extension were associated with better survival. CR according to mRECIST criteria was a predictor of better 1-year survival (100% vs. 64%, P < 0.05). Conclusion: BCLC A and CR according to mRECIST criteria predict improved 1-year survival in patients with HCC treated with TACE-DEB. Further studies are needed to evaluate other predictors of survival and to determine if tumor response predicts long-term survival.

关键词： Hepatocellular Carcinoma mRECIST Criteria Transarterial Chemoembolization Overall Survival Drug-Eluting Beads

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Haemochromatosis revisited

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World Journal of Hepatology 2022年第11期14卷 1931-1939页

作者： aline Morgan Alvarenga Pierre Brissot Paulo Caleb Junior Lima santos Department of Pharmacology-Escola Paulista de Medicina Universidade Federal de São PauloSão Paulo 04044-020Brazil University of Rennes1 Rennes 35065France

Haemochromatosis is a genetic disease caused by hepcidin deficiency,responsible for an increase in intestinal iron *** is associated with homozygosity for the HFE ***282Tyr ***,rare cases of haemochromatosis(non-HFE haemochromatosis)can also be caused by path-ogenic variants in other genes(such as HJV,HAMP,TFR2 and SLC40A1).A working group of the International Society for the Study of Iron in Biology and Medicine(BIOIRON Society)has concluded that the classification based in different molecular subtypes is difficult to be adopted in clinical practice and has proposed a new classification approaching clinical questions and molecular *** aim of the present review is to provide an update on classification,pathophysiology and therapeutic recommendations.

关键词： Haemochromatosis Iron overload HFE Molecular diagnosis Hepcidin

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Hydrological variability and long-term floristic-structural modifications in different habitats of a tropical semi-deciduous forest

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Journal of Forestry Research 2022年第3期33卷 801-811页

作者： Alisson Borges Miranda santos Vinicius Andrade Maia Cléber Rodrigo de Souza Natália de Aguiar-Campos Aurélio de Jesus Rodrigues Pais Wilder Bento da Silva Nathalle cristine Alencar Fagundes Jean Daniel Morel Rubens Manoel dos santos Department of Forestry Sciences Federal University of LavrasCampus UniversitárioC.P.3037LavrasBrazil Faculty of Environmental Engineering and Natural Resources Zambeze UniversityChimoioC.P.2400Mozambique Biological Sciences Universidade do Estado de Minas GeraisUnidade ItuiutabaAv.Antônio Carlos 6627Ituiutaba31270-901Brazil Department of Biology Federal University of LavrasUniversity campusC.P.3037Lavras37200-000Brazil

Shifts in hydrological regimes alter river flow rates and flood pulses, decrease environmental heterogeneity and the floristic-structural complexity of associated plant communities. We tested the hypothesis that drought events affect plant community composition and structure at a small-scale within a riparian fragment towards a reduction in floristic-structural complexity. The tree community was sampled in three habitats (wet, transitional and dry) and monitored in seven inventories carried out between 1991 and 2018. Hydrological variations were evaluated through annual rainfalls, river flow rates and water level data. The species richness and the detrended correspondence analysis axes were used to characterise the temporal modifications in floristic composition. Community structure was described in terms of biomass: accumulated, growth of survivors, mortality and recruitment. Generalised linear mixed models were fitted to evaluate the effects of time and environment in community. It was concluded that the climate has become drier in recent years due to declining precipitation that has affected flow rates and water levels. The floristic-structural complexity of the study fragment was maintained during the monitoring period. However, prolonged and extreme drought events displayed the potential to impact floristic-structural patterns.

关键词： Forest dynamics Climate changes Semi-deciduous seasonal forest Temporal change Functioning communities

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Peroxisome proliferator-activated receptors as targets to treat metabolic diseases:Focus on the adipose tissue,liver,and pancreas

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World Journal of Gastroenterology 2023年第26期29卷 4136-4155页

作者： Henrique Souza-Tavares Carolline santos Miranda Isabela Macedo Lopes Vasques-Monteiro Cristian Sandoval Daiana Araujo Santana-Oliveira Flavia Maria Silva-Veiga aline Fernandes-da-Silva Vanessa Souza-Mello Department of Anatomy Rio de Janeiro State UniversityRio de Janeiro 20551030Brazil Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásOsorno 5310431Chile Departamento de Ciencias Preclínicas Universidad de la FronteraTemuco 4780000Chile

The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease *** prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its *** adipose tissue is the initial site of obesity *** excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other *** pancreas is one of the organs most affected by *** lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long *** for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic *** silent disease affects around 30%of the worldwide population and can evolve into end-stage liver *** therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM *** PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial *** review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.

关键词： Obesity Insulin resistance Peroxisome proliferator-activated receptors Pancreas Hepatic steatosis Adipose tissue

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High Order of Accuracy for Poisson Equation Obtained by Grouping of Repeated Richardson Extrapolation with Fourth Order Schemes

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Computer Modeling in Engineering & Sciences 2021年第8期128卷 699-715页

作者： Luciano Pereira da Silva Bruno Benato Rutyna aline Roberta santos Righi Marcio Augusto Villela Pinto Graduate Program in Numerical Methods in Engineering Federal University of ParanaCuritiba81531-980Brazil Graduate Program in Space Sciences and Technologies Aeronautics Institute of TechnologySao Jose dos Campos12228-900Brazil Department of Mechanical Engineering Federal University of ParanaCuritiba81531-980Brazil

In this article,we improve the order of precision of the two-dimensional Poisson equation by combining extrapolation techniques with high order *** high order solutions obtained traditionally generate non-sparse matrices and the calculation time is very *** can obtain sparse matrices by applying compact *** this article,we compare compact and exponential finite difference schemes of fourth *** numerical solutions are calculated in quadruple precision(Real*16 or extended precision)in FORTRAN language,and iteratively obtained until reaching the round-off error magnitude around 1.0E−*** procedure is performed to ensure that there is no iteration *** Repeated Richardson Extrapolation(RRE)method combines numerical solutions in different grids,determining higher orders of *** main contribution of this work is based on a process that initializes with fourth order solutions combining with RRE in order to find solutions of sixth,eighth,and tenth order of *** multigrid Full Approximation Scheme(FAS)is also applied to accelerate the convergence and obtain the numerical solutions on the fine grids.

关键词： Tenth order accuracy RRE compact scheme exponential scheme multigrid finite difference

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The role of environmental temperature on movement patterns of giant anteaters

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Integrative Zoology 2022年第2期17卷 285-296页

作者： aline GIROUX Zaida ORTEGA Alessandra BERTASSONI Arnaud Léonard Jean DESBIEZ Danilo KLUYBER Gabriel Favero MASSOCATO Guilherme DE MIRANDA Guilherme MOURÃO Luciana SURITA Nina ATTIAS Rita de Cassia BIANCHI Vinícius Peron de Oliveira GASPAROTTO Luiz Gustavo Rodrigues OLIVEIRA-santos Ecology Department Federal University of Mato Grosso do Sul(UFMS)Campo GrandeMato Grosso do SulBrazil Post Graduate Program of Ecology and Evolution Federal University of Goiás(UFG)GoiâniaGoiásBrazil Institute of Research and Conservation of Anteaters in Brazil(PROJETO TAMANDUÁ) ParnaíbaPiauíBrazil Institute for the Conservation of Wild Animals(ICAS) Campo GrandeMato Grosso do SulBrazil Royal Zoological Society of Scotland(RZSS) MurrayfieldEdinburghUK Institute for Ecological Research(IPÊ) NazaréPaulistaSão PauloBrazil Naples Zoo at Caribbean Gardens NaplesFloridaUSA The Houston Zoo HoustonTexasUSA National Institute of Criminalistics-Federal Police BrasíliaBrazil Embrapa Pantanal CorumbáMato Grosso do SulBrazil Natural Resources Graduate Program(PRONAT)-Federal University of Roraima(UFRR) Boa VistaRoraimaBrazil Animal Biology Graduate Program Federal University of Mato Grosso do Sul(UFMS)Campo GrandeMato Grosso do SulBrazil Animal Biology Department São Paulo State University(UNESP)São Josédo Rio PretoSão PauloBrazil Department of Preventive Veterinary Medicine and Animal Health School of Veterinary MedicineUniversity of São Paulo(USP)São PauloSPBrazil Brazilian Institute for Conservation Medicine(TRÍADE) RecifePernambucoBrazil

Mammals can show conspicuous behavioral responses to thermal variation,including changes in movement *** used an integrative approach to understand how environmental temperature can drive the movement behavior of a mammal with low capacity for physiological thermoregulation,the giant anteater(Myrmecophaga tridactyla).We tracked 52 giant anteaters in 7 areas throughout the Brazilian *** estimated the distance moved,area used,use of forest areas,and mean environmental temperature for each monitoring day of each *** modeled these data with Mixed Structural Equations—considering the possible interactions between our variables and controlling for sex and body *** anteaters reduced displacement and increased forest use with decreasing environmental temperature,probably because of their low body heat *** is possible that they reduce distance moved and area used by reducing the duration of *** decreasing temperature,forest habitats become warmer than open ones,besides buffer rain and chilly *** displacement and using forests are important strategies to reduce body heat loss and the energetic costs of ***,decreasing movement can limit food access and,consequently,***,we highlight the importance of forests as thermal *** increasing frequency and intensity of extreme weather events,we showed the need to preserve forest patches to offer suitable conditions for tropical mammals’behavioral *** this context,policies favoring deforestation on Brazilian territory are especially ***,we emphasize the need of integrative approaches to understand the complex interactions between organisms and the environment.

关键词： behavioral thermoregulation biologging habitat use mixed structural equations movement ecology

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Nutrition and exercise can attenuate inflammatory and psychobiological changes in hypoxia?

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Asian Pacific Journal of Tropical Biomedicine 2017年第1期7卷 86-90页

作者： aline Venticinque Caris Wanessa Ysis Valdir de Aquino Lemos Ricardo Bottura Ronaldo Vagner Thomatieli dos santos Department of Psychobiology Federal University of Sao Paulo(UNIFESP)SantosBrazil Department of Bioscience Federal University of Sao Paulo(UNIFESP)SantosBrazil

Exposure to hypoxia causes damage in several physiological systems, whose tissues are dependent on the O2 supply. Recently, there has been growing attention on the immunosuppressive and inflammatory potential of the hypoxia, including stimulation, nuclear factor kappa B pathway in macrophages and Th2 response from lymphocytes. These changes may result in transient immunosuppression and happen at the same time to worsening of cognition and other psychobiological aspects. Furthermore, exercise and nutrition, especially glutamine supplementation may provide important role, not pharmacological partially reversing the effects of hypoxia. In fact, recent studies show that moderate exercise can improve cognition in people exposed to hypoxia while the exercise associated with glutamine supplementation can reverse the increase in inflammatory markers and the Th1/Th2 balance. This review aims to bring the light of the discussion about nonpharmacological ways to prevent the effects of hypoxia on the connection between the immune system and the central nervous system.

关键词： Physical exercise High altitude Inflammation Cognition Glutamine

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Impacts of land use and land cover changes on hydrological processes and sediment yield determined using the SWAT model

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International Journal of Sediment Research 2022年第1期37卷 54-69页

作者： Edivaldo Afonso de Oliveira Serr?o Madson Tavares Silva Thomás Rocha Ferreira Lorena Concei??o Paiva de Ataide Cleber Assis dos santos aline Maria Meiguins de Lima Vicente de Paulo Rodrigues da Silva Francisco de Assis Salviano de Sousa Denis José Cardoso Gomes Academic Unit of Atmospheric Sciences Federal University of Campina Grande Department of Physics Center for Natural and Exact Sciences Federal University of Santa Maria Institute of Technology Civil Engineering Graduate Program Federal University of Pará Earth System Science Center National Institute of Space Research Institute of Geosciences Federal University of Pará

Land use and land cover (LULC) changes strongly affect local hydrology and sediment *** current study focused on a basin in the Brazilian Amazon and had the following three objectives:(1) to perform an effective diagnosis of flow and sediment yield,(2) to evaluate the impacts of LULC changes over the last 40 years on the hydro-sedimentological variables,and (3) to investigate the impacts of the possible trends or breaking points in the flow,surface runoff,and sediment yield *** Soil and Water Assessment Tool (SWAT) model validation showed that the simulated results were consistent with the data measured in the dynamic reproduction of flow ***,changes in LULC altered surface runoff,sediment yield,and flow according to the Mann-Kendall and Pettitt non-parametric *** was also observed that the sub-basins in which pastureland is predominant are more susceptible to increased surface runoff and sediment *** to trend and homogeneity tests,these sub-basins had break points in the time series of these *** the other hand,in the sub-basins whose land cover is predominantly forest,the time series is homogeneous and *** current study highlighted the impacts that 40 years of LULC changes in an Amazonian basin had on hydro-sedimentological variables,which,in turn,can play an important role in changing the hydrological cycle,consequently these changes can also impact diverse human activities in the region,such as agribusiness,livestock,energy production,food security,and public water ***,it is concluded that the SWAT model is a good estimator of hydro-sedimentological processes in Amazonian basins and can be used by decision makers in the management of water and environmental resources.

关键词： Hydrological modeling Sediment yield Amazon basin SWAT model

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Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

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World Journal of Hepatology 2023年第11期15卷 1237-1249页

作者： Adriana Camargo Ferrasi Samara Vitória Granja Lima aline Faria Galvani Jeany Delafiori Flavia Luísa Dias-Audibert Rodrigo Ramos Catharino Giovanni Faria Silva Roberta Rodrigues Praxedes Driele Bretones santos Dayane Trevisan de Macedo Almeida Estela Oliveira Lima Department of Internal Medicine Sao Paulo State UniversityBotucatu 18618-686Brazil Innovare Biomarkers Laboratory University of CampinasCampinas 13083-877Brazil

BACKGROUND Chronic Hepatitis C(CHC)affects 71 million people globally and leads to liver issues such as fibrosis,cirrhosis,cancer,and death.A better understanding and prognosis of liver involvement are vital to reduce morbidity and *** accurate identification of the fibrosis stage is crucial for making treatment decisions and predicting *** used to grade fibrosis include histological analysis and imaging but have *** markers such as molecular biomarkers can offer valuable insights into *** To identify potential biomarkers that might stratify these lesions and add information about the molecular mechanisms involved in the *** Plasma samples were collected from 46 patients with hepatitis C and classified into fibrosis grades F1(n=13),F2(n=12),F3(n=6),and F4(n=15).To ensure that the identified biomarkers were exclusive to liver lesions(CHC fibrosis),healthy volunteer participants(n=50)were also *** untargeted metabolomic technique was used to analyze the plasma metabolites using mass spectrometry and database *** analyses were performed to identify differential biomarkers among *** Six differential metabolites were identified in each grade of *** six-metabolite profile was able to establish a clustering tendency in patients with the same grade of fibrosis;thus,they showed greater efficiency in discriminating *** This study suggests that some of the observed biomarkers,once validated,have the potential to be applied as prognostic ***,it suggests that liquid biopsy analyses of plasma metabolites are a good source of molecular biomarkers capable of stratifying patients with CHC according to fibrosis grade.

关键词： Chronic Hepatitis C Fibrosis Metabolome Biomarkers Plasma Liquid biopsy

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