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

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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

A different vision of translational research in biomarker discovery: a pilot study on circulatory mitochondrial proteins as Parkinson’s disease potential biomarkers

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Translational Neurodegeneration 2020年第2期9卷 118-131页

作者： sandra I.Anjo Patrícia Valério dos santos Luiza Rosado Graça Baltazar Inês Baldeiras Diana Pires Andreia Gomes cristina Januário Miguel Castelo-Branco Mário Grãos Bruno Manadas CNC-Center for Neuroscience and Cell Biology University of CoimbraCoimbraPortugal Faculty of Medicine University of CoimbraCoimbraPortugal Centro de Investigação em Ciências da Saúde(CICS-UBI) Universidade da Beira InteriorCovilhãPortugal Centro Hospitalar Cova da Beira E.P.ECovilhãPortugal Neurology Department Centro Hospitalar e Universitário de CoimbraCoimbraPortugal Coimbra Institute for Biomedical Imaging and Translational Research(CIBIT) CoimbraPortugal Biocant Biotechnology Transfer AssociationCantanhedePortugal Institute for Interdisciplinary Research University of Coimbra(IIIUC)CoimbraPortugal

Background The identification of circulating biomarkers that closely correlate with Parkinson’s Disease(PD)has failed several times in the ***,in this pilot study,a translational approach was conducted,allowing the evaluation of the plasma levels of two mitochondrial-related proteins,whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched *** The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions,followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two *** pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD *** From the secretome analysis,several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two ***,two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched ***,a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two *** proteins are associated with apoptotic mitochondrial changes,which may correspond to potential indicators of cell ***,one of these proteins,the VPS35 protein,was reported in plasma for the first time,and its quantification was only possible due to its previous identification in the secretome *** In this work,an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases,in the present case Parkinson’s *** novelty and success of this pilot study may arise from the combination of:i)a translational research pipeline,where plasma samples are interrogated using knowledge previously ob

关键词： Mitochondrial-related proteins SWATH-MS Parkinson's disease Biomarker discovery Blood-biomarker Secretomes Oxidative stress

Comparison of morphological and functional outcomes of mouse sciatic nerve repair with three biodegradable polymer conduits containing poly (lactic acid)

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Neural Regeneration Research 2018年第10期13卷 1811-1819页

作者： Fernanda Marques Pestana Rui C.C.Domingues Júlia Teixeira Oliveira Daniela F.P.A.Durco Camila Oliveira Goulart Henrique rocha Mendonca Anne Caroline Rodrigues dos santos Natália Tavares de Campos Beatriz Theodoro da Silva cristina Cardoso Pereira Cristiano Piacsek Borges Ana Maria Blanco Martinez Pós Graduacao em Ciências Morfológicas Instituto de Ciências Biomédicas-UFRJRio de Janeiro RJ Brazil Anatomia Patológica-Faculdade de Medicina-HUCFF-UFRJ Rio de Janeiro RJ Brazil Laboratório de Neurodegeneracao e Reparo-Faculdade de Medicina-HUCFF-UFRJ Rio de Janeiro RJ Brazil Programa de Eng. Química COPPE-UFRJRio de Janeiro Brazil Polo Universitário de Macaé Laboratório Integrado de Produtos Bioativos e BiociênciasMacaê UFRJ Brazil

Poly（lactic acid）（PLA）-containing nerve guidance conduits（NGCs） are currently being investigated for nerve repair as an alternative to autograft, which leads to permanent functional impairment in the territory innervated by the removed nerve. Combination of polymers modifies the physical properties of the conduits, altering their nerve-guidance properties. Conduits made from PLA-only or combined with other polymers have been used successfully for nerve repair, but their efficiency has not been compared. We compared the morphological and functional outcomes of peripheral nerve repair by using NGCs made of poly（lactic acid） and combined or not with polycaprolactone（PLA/PCL） or polyvinylpyrrolidone（PLA/PVP）. To assess the functional recovery, we employed a mechanical hyperalgesia analysis, sciatic functional index（SFI）, and electroneuromyography. The mechanical hyperalgesia analysis showed that the PLA group improved more rapidly than the PLA/PVP and PLA/PCL groups; similarly, in the electroneuromyography assay, the PLA group exhibited higher amplitude than the PLA/PCL and PLA/PVP groups. However, the SFI improvement rates did not differ among the groups. Morphologically, the PLA group showed more vascularization, while the nerve fiber regeneration did not differ among the groups. In conclusion, the PLA-only conduits were superior to the other NGCs tested for nerve repair.

关键词： sciatic nerve tubulization biodegradable conduit poly(lactic acid) regeneration

Evaluation of the Therapeutic Response and Improvement in the Quality of Life of the Patient with Darier Disease to Acitretin through an Analogy between Close Relatives

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Journal of Biosciences and Medicines 2017年第8期5卷 48-54页

作者： Thiago Sande Miguel Mateus de Oliveira Reis Bruno Fonseca dos santos Aline da Silva rocha Nayrton Kalys Cruz dos Anjos Lívia cristina de Melo Pino Daniel Almeida da Costa The Medical School at the Center of Higher Education of Valenca Valenca Brazil

Darier disease (DD), also known as follicular keratosis, is a rare autosomal dominant hereditary acantholytic dermatosis caused by a mutation in the ATP2A2 gene. Skin lesions are characterized by persistent confluent papules, preferentially located on the seborrheic areas of the face, chest and back. The hands, feet and nails are also commonly affected. DD has a chronic course with frequent relapses. Their treatment is often difficult and unsatisfactory. We present the case of a 54-year-old male with a history of keratotic papules with a brownish-black color, with a foul-smelling, pruritic and ardent appearance on the back and trunk, since the age of 19, which worsen in the summer. His 27-year-old daughter has a similar picture with her skin lesions started at age of 17 in the region below the breast, back, trunk, feet and hands. After the skin biopsy, the diagnosis was confirmed and acitretin 30 mg/day was instituted. The importance of this case report is to alert health professionals that the diagnosis of DD should be considered in family members of patients, especially those in the first degree, and also in patients with follicular keratolytic dermatoses, being an important differential diagnosis of this group of patients diseases.

关键词： Darier’s Disease Follicular Keratosis Hereditary Dermatosis

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease

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世界胃肠病学杂志：英文版 2015年第29期21卷 8927-8934页

作者： Daniele Santetti Maria Inês de Albuquerque Wilasco cristina Toscani Leal Dornelles Isabel cristina Ribas Werlang Fernanda Urruth Fontella Carlos Oscar Kieling Jorge Luiz dos santos sandra Maria Goncalves Vieira Helena Ayako Sueno Goldani Post-Graduate Program of Child and Adolescent Health Faculdade de MedicinaUniversidade Federal do Rio Grande do SulPorto Alegre Nutrition Service Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto Alegre Laboratory of Translational Pediatrics-NESCA Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto Alegre Pediatric Hepatology Unit Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto Alegre Pediatric Gastroenterology Unit Hospital de Clínicas de Porto Alegre and Post-Graduate Program of Child and Adolescent HealthFaculdade de MedicinaUniversidade Federal do Rio Grande do SulPorto Alegre

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver ***: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease(MELD) and Pediatric End Stage Liver Disease(PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition(Z-score <-1.00) and malnutrition(Z-score <-2.00). Interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median(25th-75 th centile) age of the study population was 60(17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease(72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values were increased in patients at nutritional risk(34.9%) compared with those who were well-nourished [7.12(0.58-34.23) pg/m L vs 1.63(0.53-3.43) pg/m L; P = 0.02], correlating inversely with triceps skinfold-for-age z-score(rs =-0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score(P = 0.001).

关键词： Cytokines Interleukin-6 Malnutrition Cirrhosis Child

Role of Cognitive Behavioral Therapy in Fibromyalgia: A Systematic Review

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Open Journal of Rheumatology and Autoimmune Diseases 2021年第4期11卷 169-187页

作者： Heloisa Lima Heller Aline Rizzo Borges Luís Otávio Amarante Franco João Pedro De Oliveira Aucelio Marcos Igor Albanaz Vargas Rebeca Naoum Lorga Mirella Bastos Sales Natália Vargas Do Nascimento Gabriela Furlan Ribeiro Barbosa Netto Beatriz Carneiro Passos Beatriz Pires Paes Beatriz Toledo Mendes Bruna De Paula Gonçalves Sousa Lyra Ciro Moisés Oliveira Vieira dos santos Gustavo Araújo Do Nascimento santos Maria Luiza Pimentel De Oliveira Matheus Macêdo Da Silva Maurício Silva De Jesus Paulo Ricardo Guimaraes rocha Storni Tamires Martinelli De Oliveira Ferraz Viviane cristina Uliana Peterle Ana Paula Monteiro Gomides Reis Centro Universitário de Brasília Brasília Brazil Universidade Católica de Brasília Brasília Brazil Centro Universitário Euro Americano Brasília Brazil

A literature search of articles from 2002-2019 was performed using Medline, Embase, Cochrane, LILACS, IBECS, CRD, and Epistemonikos databases, to analyze the effects of Cognitive-Behavioral Therapy (CBT) in the treatment of fibromyalgia. Twenty-seven articles were selected in which CBT was performed exclusively by specialist physicians, associated or not with conventional pharmacological treatment and/or physical exercise. In most articles, CBT worked with self-knowledge and cognitive restructuring, attempting to reduce pain perception, and it showed a general improvement in daily activities by decreasing patient’s limitations, such as morning stiffness. The literature showed significant correlations of CBT in pain processing over time. When CBT was compared to conventional pharmacological therapy, a certain superiority of CBT could be observed concerning the quality of life, catastrophizing, and acceptance of pain. However, when they were simultaneously applied, this improvement in quality of life was not observed.

关键词： Cognitive Behavioral Therapy Fibromyalgia Pain