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Antitumor Effect of cationic INKKI Peptide from Bovine β-casein on Melanoma B16f10

Journal of cancer Therapy 2012年第4期3卷 237-244页

作者： Ricardo Alexandre Azevedo Adilson Kleber ferreira Aline Vivian Vatti Auada Kerly fernanda Mesquita Pasqualoto Rafael marques-Porto Durvanei Augusto Maria Ivo Lebrun Butantan Institute Biochemistry and Biophysical Laboratory Sao Paulo Brazil

cationic peptide with the sequence INKKI 41-45 was isolated from bovine β-casein after tryptic hydrolysis and synthetized. The aim of this work was to evaluate the antiproliferative activity in vitro and antitumor effect in animal model. The in vitro cytotoxicity was evaluated on B16f10 melanoma cells by MTT assay. Detection of apoptosis was measured using the annexin V/PI double staining and cell cycle analysis performed flow cytometry. caspase-3 activity was analyzed with substrate specific fluorogenic DEVD-McA. In vivo, antitumor activity was evaluated in B16f10 melanoma tumor-bearing c57BL/6J mice. The animals were treated with 55 mg/kg INKKI administered into peritumoral region, while control group received saline solution. The following antitumor parameters were examined: tumor volume, number of metastases, tumor delayed time, tumor doubling time. Histological analyses were performed with H & E staining. The results showed that INKKI induced dose-response cytotoxicity selective for B16f10 melanoma cells (Ic50 1.7 μM) and did not present cytotoxic effects for fN1 fibroblast cells. INKKI-induced apoptosis detected trough of annexin V/PI assay and it was accompanied with an increase of sub-G1 apoptotic fractions and significant increase of caspase-3 cleavage. The tumor-bearing mice treated with INKKI showed a significant reduction in tumor volume of 72.62% and decreased of metastasis number loci. In addition, INKKI caused a significant delay in tumor growth and prolonged the tumor doubling time. Histological analysis revealed an increased of necrosis areas and reduction of tumor cells in tumor treated with INKKI, it was a many hallmark of its antitumor effects observed from in vivo experiments. In conclusion, we show that INKKI is a peptide that could be considered a new putative candidate development to anticancer therapy drug.

关键词： β-casein Peptide Apoptosis Metastasis Tumor Growth Melanoma

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Triiodothyronine and breast cancer

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World Journal of clinical Oncology 2014年第3期5卷 503-508页

作者： Maria Teresa De Sibio Miriane de Oliveira fernanda cristina fontes Moretto Regiane marques castro Olimpio Sandro José conde Aline carbonera Luvizon célia Regina Nogueira Department of Internal Medicine Botucatu Medical SchoolUniv Estadual PaulistaUNESPBotucatuSP 18618-970Brazil Department of Pathology Botucatu Medical School Univ Estadual Paulista-UNESP Botucatu SP 18618-970Brazil

The thyroid hormones(THs), triiodothyronine(T3) and thyroxine(T4), are essential for survival; they are involved in the processes of development, growth, and metabolism. In addition to hyperthyroidism or hypothyroidism, THs are involved in other diseases. The role of THs in the development and differentiation of mammary epithelium is well established; however, their specific role in the pathogenesis of breast cancer(Bc) is controversial. Steroid hormones affect many human cancers and the abnormal responsiveness of the mammary epithelial cells to estradiol(E2) in particular is known to be an important cause for the development and progression of Bc. The proliferative effect of T3 has been demonstrated in various types of cancer. In Bc cell lines, T3 may foster the conditions for tumor proliferation and increase the effect of cell proliferation by E2; thus, T3 may play a role in the developmentand progression of Bc. Studies show that T3 has effects similar to E2 in Bc cell lines. Despite controversy regarding the relationship between thyroid disturbances and the incidence of Bc, studies show that thyroid status may influence the development of tumor, proliferation and metastasis.

关键词： Thyroid hormone Triiodothyronine Breast cancer Mammary gland and metabolism

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PNPLA3 and TM6Sf2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease

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World Journal of Hepatology 2020年第10期12卷 792-806页

作者： Quelson coelho Lisboa Mateus Jorge Nardelli Patrícia de Araújo Pereira Débora marques Miranda Stephanie Nunes Ribeiro Raissa Soares Neves costa camila Azevedo Versiani Paula Vieira Teixeira Vidigal Teresa cristina de Abreu ferrari claudia Alves couto Departament de clínica Médica Faculty of MedicineUniversidade Federal de Minas GeraisBelo Horizonte 30130100Brazil

BAcKGROUND Nonalcoholic fatty liver disease(NAfLD)is becoming the most common chronic liver disease worldwide,with significant morbidity associated with nonalcoholic steatohepatitis(NASH).Genome-wide association studies demonstrated that the variants rs738409 c/G in the PNPLA3 and rs58542926 c/T in the TM6Sf2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAfLD *** To investigate PNPLA3 and TM6Sf2 genotype frequency and their association with NAfLD development and progression in Brazilian *** This cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in *** case patients(n=148)were confirmed to have NAfLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver *** to the clinical protocol,patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis(n=65).Steatohepatitis was confirmed in 54 *** who did not have biopsy indication or NASH on histology were considered to have simple steatosis(n=94).The control group(n=137)was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical *** individuals underwent PNPLA3 and TM6Sf2 genotype *** PNPLA3 cc,cG and GG genotype frequencies were 37%,44%and 19%,respectively,in NAfLD patients and were 58%,31%and 10%in controls(Pfor gender,age,body mass index and type 2 diabetes mellitus,the G allele increased the chance of NAfLD(OR=1.69,95%cI:1.21-2.36,P=0.002)and NASH(OR=3.50,95%cI:1.84-6.64,Pchance of NASH was even higher with GG homozygosis(OR=5.53,95%cI:2.04-14.92,P=0.001).No association was found between G allele and the features of metabolic *** histological assessment,PNPLA3 genoty

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Genetic variation Single nucleotide polymorphism Genotype Brazil fibrosis

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白癜风患者合并Sézary综合征的发病机制

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世界核心医学期刊文摘（皮肤病学分册） 2006年第3期2卷 44-45页

作者： Knol A.c. Quéreux G. marques-Briand S. B. Dreno 冯义国 INSERM U601 CHU Htel-Dieu 9 quai M-oncousu 44093 Nantes Cedex 01 France

Patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (cTcL) remain rare and it is not known whether some T-cell subpopulations of cTcL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with Sé zary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient cOS transfection assay that permits an estimation of cD8 T-cell responses against a- large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A 23 context. Our study supports the concept that vitiligo that has developed during the evolution of a cTcL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.

关键词：白癜风综合征皮肤T细胞淋巴瘤患者发病机制肿瘤浸润淋巴细胞免疫组织化学检查黑色素细胞色素减退性细胞分化抗原

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Effect of Organic fertilizer Doses on the Plant Growth,Essential Oil Production and chemical Substances of ＂carqueja＂ over Two Harvest Moments

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Journal of Agricultural Science and Technology(B) 2017年第2期7卷 114-124页

作者： Daniel Garcia Paulo Sérgio Siberti da Silva Marcos Roberto furlan Monica Tiho chisaki Isobe Marcia Ortiz May marques Lin chau Ming Horticulture Department Faculty of Agronomic Sciences (FCA) Sao Paulo State University "J~lio de Mesquita Filho"18.610-307 Botucatu Sao Paulo Brazil Agronomy Department Cantareira Faculty (FIC) 03.020-000 Sao Paulo Brazil Agronomy Department University of Mato Grosso State 78.200-000 Caceres Mato Grosso Brazil Natural Products Department Agronomic Institute of Campinas (IA C) 13.001-970 Campinas Sao Paulo Brazil

This study aimed to investigate, for the first time, the plant growth, essential oil content and their chemical substances ofBaccharis trimera （Less.） Dc., the first Brazilian variety of medicinal plant, in response to five doses of organic fertilizer （0, 10, 20,30, 40 and 50 ton/ha） over two harvest moments-120 d and 242 d after transplanting （DAT）. The work was carried out fromfebruary to October 2011 at the experimental farm of the Sao Paulo State University ＂Julio de Mesquita filho＂（UNESP）, *** seedlings of B. trimera var. cPQBA-1 were respectively transplanted into experiment plots under six treatments： 0, 10, 20, 30,40 and 50 ton/ha of organic fertilizer. Each treatment had four replications and each plot consisted of 12 plants. Then they wereharvested at 120 DAT and 242 DAT, and the essential oil were extracted by hydrodistillation and analyzed by gas *** results were subjected to analysis of variance and the means were analysed using Tukey＇s test （5%） followed by a regressionanalysis. The fertilizer dose significantly influenced the height of the plants in the second harvest, while the higher dose of organicfertilizer positively impacted the essential oil content in the first harvest. Also, the level of organic fertilizer was directly correlatedwith the production of dry matter during the regrowth. Twenty-seven substances were identified in the essential oil samples, and themajor components were： bicyclogermacrene, trans-caryophyllene, germacrene-D, spathulenol and caryophyllene oxide. Thesefindings suggest that to obtain higher yields of dry matter ofB. trimera, it should be harvested around 242 DAT and organic fertilizershould be applied approximately to 50 ton/ha. furthermore, higher doses of organic fertilizer and harvest at 120 DAT is able toincrease the essential oil content.

关键词： Baccharis trimera, Brazilian medicinal plant, dry matter, chemical substances, bicyclogermacrene.

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Respiratory Muscle Strength Evaluation in Healthy Adult and Elderly Women—Respiratory Muscle Strength Assessment in Adult and Elderly

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Health 2018年第8期10卷 1031-1036页

作者： Maria clara de Souza Pereira Gama Maciel cássio Daniel Araújo da Silva fernanda figueiroa Sanchez Jamilly Reboucas Demosthenes marques Pablo costa cortez camila Miriam Suemi Sato Barros do Amaral Naylla Morais de Souza Roberta Lins Goncalves federal University of Amazonas-UfAM ManausBrazil

Measurement of respiratory muscle strength is performed through static measurements of maximal respiratory pressures and is an important tool for determining the existence and prognosis of neuromuscular and pulmonary disorders, such as weakness or fatigue of this musculature. Objectives: To evaluate and compare respiratory muscle strength among healthy adult and elderly women. Methods: A total of 163 healthy women were recruited through convenience sampling at the family centers of the city of Manaus (AM, Brazil), divided into two groups: adult women (age 20 - 59 years) and elderly women (over 60 years of age). The evaluation was performed by Manovacuometry, in order to measure the maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP). for statistical analysis we used the Student’s T test, considering significant p value ≤ 0.05. Results: The final sample consisted of 116 adult women and 47 elderly women. The mean age in the group of women between 20 - 59 years was 44.5 ± 12 and the elderly group was 65 ± 6.6. MIP values in adult women were significantly higher when compared to the elderly (−108 ± 5.3 cmH2O × −79.5 ± 4 cmH2O, p = 0.0014, respectively). The same behavior was observed in the evaluation of MEP (87.1 ± 2.9 cmH2O in adults and 69.8 ± 3.5 cmH2O in the elderly;p = 0.0008). conclusion: The results indicate that inspiratory and expiratory muscle strength is lower in older women, suggesting that the aging process tends to interfere with those muscles, resulting in altered respiratory system function.

关键词： Muscular Strength Evaluation Respiratory Muscles Aging

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Metabolic Syndrome and Pregnancy, Its Prevalence, Obstetrical and Newborns complications

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Open Journal of Obstetrics and Gynecology 2015年第11期5卷 618-625页

作者： Hamilton dos Prazeres Tavares Mariana Alvarez Arantes Suelma Beatriz marques Prata Tavares Joelcio francisco Abbade D. c. D. Meirelles dosDébora cristina Damasceno Meirelles dos Santos Iracema de Mattos Paranhos calderon Marilza Vieira cunha Rudge PhD Student in Gynecology Obstetrics and Mastology at the Botucatu Medical School Unesp Paulista State University Botucatu SP Brazil Medical Specialist in Gynaecology and Obstetrics and Boss of Department of Gynecology and Obstetrics of the Municipal Hospital of Huambo Huambo Angola Assistant Professor of Obstetrics Botucatu Medical School Unesp Paulista State University Botucatu SP Brazil PhD Department of Gynecology and Obstetrics Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Unesp Paulista State University Botucatu SP Brazil full Professor of Obstetrics in Botucatu Medical School Unesp Paulista State University Botucatu SP Brazil

Background: The metabolic syndrome affects more and more global people. Although it shows increasing prevalence in general population, the syndrome affects more women than men, what makes its risk of being developed during pregnancy period. Also, possible perinatal adverse effects are always lurking. Objective: the objective was demonstrated what’s new in literature on metabolic syndrome and pregnancy. Methods: A literature review was performed to extract the articles published on metabolic syndrome and pregnancy, its prevalence, obstetrical complications and its perinatal adverse effects. This review was conducted by online researching in PubMed, Lilacs, Medline, Embase, Scopus, Medscape, Libertas Academica and cINAHL database, Science database and also by researches in books. 27 selected articles on metabolic syndrome after this research were all published between 1988 and 2015. Results: Among those 27 articles and two books studied, SM rate in obstetric population ranged from 3% to 42% depending on the previously manifested components of the syndrome, age and region. Women with previously manifested components showed more adverse perinatal effects. conclusion: Women with pregestational DM or SM and SM develop more during pregnancy, obstetric complications and adverse perinatal outcomes.

关键词： Metabolic Syndrome Pregnancy Adverse Perinatal Outcomes

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Virulence factors in Methicillin-Resistant Staphylococcus aureus Isolated from IcU Units in Brazil

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Advances in Microbiology 2014年第4期4卷 207-215页

作者： Simone G.Souza Guilherme B.campos Pollianna S.Oliveira Daniel S.Sousa Danilo c.c.Da Silva Verena M.Santos Aline T.Amorim Angelita M.O.G.Santos Jorge Timenetsky Mariluze P.cruz Regiane Yatsuda Lucas M.marques Instituto Multidisciplinar em Saúde Núcleo de Tecnologia em SaúdeUniversidade Federal da BahiaVitória da ConquistaBrazil Instituto de ciências Biomédicas Departamento de MicrobiologiaUniversidade de Sao PauloSao PauloBrazil

Species of Staphylococcus are common in hospital infection (HI). Methicillin resistant S. aureus (MRSA) has also become a serious problem in Brazilian HI. The aim of this study was to characterize the pathogenicity of methicillin-resistant S. aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) isolated in public hospitals. The clinical isolates were obtained from intensive care unit. The MRSA and MSSA strains were genotyped by PcR for detection genes related to virulence factors. Moreover, the strains were tested for biofilm formation and cytokine induction in macrophages. Three strains of MRSA (9.68%) expressed the Sea gene, one (3.23%) Seb, 17 (54.84%) Spa and seven (22.58%) had PVL. Two MSSA strains (2.98%) expressed the Sea gene, three (4.48%) Seb, 18 (26.87%) Spa and 11 (16.42%) showed positive results for the PVL gene. There was no expression of Sec and cflA between MRSA and MSSA strains. Among MRSA and MSSA isolates, none statistical differences were observed in biofilm production. The analysis of cytokine induction in the inflammatory response of J774 macrophages by MRSA and MSSA isolates did not show statistical difference. Understanding the mechanisms of pathogenesis of S. aureus could provide important clues for both preventing and treating infection caused by these organisms.

关键词： MRSA MSSA Virulence factor Hospitalar Infection

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Deep sedation during gastrointestinal endoscopy: Propofol-fentanyl and midazolam-fentanyl regimens

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World Journal of Gastroenterology 2013年第22期19卷 3439-3446页

作者： Marcos Eduardo Lera dos Santos fauze Maluf-filho Dalton marques chaves Sergio Eiji Matuguma Edson Ide Gustavo de Oliveira Luz Thiago ferreira de Souza fernanda c Simoes Pessorrusso Eduardo Guimares Hourneaux de Moura Paulo Sakai Department of Gastroenterology Hospital das Clínicas University of Sao Paulo Medical School Sao Paulo CEP 05403-900 Brazil cancer Institute of Sao Paulo State Sao Paulo CEP 01246-000 Brazil

AIM: To compare deep sedation with propofol-fentanyl and midazolam-fentanyl regimens during upper gastrointestinal endoscopy. METHODS: After obtaining approval of the research ethics committee and informed consent, 200 patients were evaluated and referred for upper gastrointestinal endoscopy. Patients were randomized to receive propofol-fentanyl or midazolam-fentanyl (n = 100/group).We assessed the level of sedation using the observer's assessment of alertness/sedation (OAA/S) score and bispectral index (BIS). We evaluated patient and physician satisfaction, as well as the recovery time and complication rates. The statistical analysis was performed using SPSS statistical software and included the MannWhitney test, χ 2 test, measurement of analysis of variance, and the κ statistic. RESULTS: The times to induction of sedation, recovery, and discharge were shorter in the propofolfentanyl group than the midazolam-fentanyl group. According to the OAA/S score, deep sedation events occurred in 25% of the propofol-fentanyl group and 11% of the midazolam-fentanyl group (P = 0.014). Additionally, deep sedation events occurred in 19% of the propofol-fentanyl group and 7% of the midazolamfentanyl group according to the BIS scale (P = 0.039). There was good concordance between the OAA/S score and BIS for both groups (κ = 0.71 and κ = 0.63, respectively). Oxygen supplementation was required in 42% of the propofol-fentanyl group and 26% of the midazolam-fentanyl group (P = 0.025). The mean time to recovery was 28.82 and 44.13 min in the propofolfentanyl and midazolam-fentanyl groups, respectively (P complications in either group. Although patients were equally satisfied with both drug combinations, physicians were more satisfied with the propofol-fentanyl combination. cONcLUSION: Deep sedation occurred with propofolfentanyl and midazolam-fentanyl, but was more frequent in the former. Recovery was faster in the propofol-fentanyl group.

关键词： Endoscopy Deep sedation Anesthetic administration Anesthetic dose Adverse effects

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Essential Oils from Lippia origanoidesKunth. and Mentha spicataL.: chemical composition, Insecticidal and Antioxidant Activities

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American Journal of Plant Sciences 2014年第9期5卷 1181-1190页

作者： Maria Luisa Teixeira Maria das G. cardoso Ana cristina S. figueiredo Jair c. Moraes franscinely A. Assis Juliana de Andrade David L. Nelson Marcos de Souza Gomes Josefina Aparecida de Souza Luiz Roberto marques de Albuquerque Department of chemistry Federal University of Lavras Lavras Brazil Department of Entomology Federal University of Lavras Lavras Brazil federal University of Vales de Jequitinhonha e Mucuri Diamantina Brazil Universidade de Lisboa Faculdade de Ciências de Lisboa Centro de Biotecnologia Vegetal Lisboa Portugal

This work describes the chemical composition of the essential oils extracted from fresh leaves of Lippia origanoides Kunth. and Mentha spicata L. and their antioxidant and insecticidal activities. The essential oils were extracted by steam distillation using a modified clevenger apparatus and subsequently analyzed by gas chromatography-flame ionization detector and gas chromatography-mass spectrometry. The antioxidant activities were determined by the β-carotene-linoleic acid method and by sequestration of the 2,2-diphenyl-1-picryl-hidrazila radical. The concentrations of the essential oils and the synthetic standard, butylated hydroxyltoluene, were 25, 50, 100, 150, 200, 250, 300 and 500 μg mL-1. Insecticidal activity was analyzed by non-preference with choice and no choice against the aphid Myzus persicae Sulzer. Gas chromatography analysis of the essential oil from Lippia origanoides Kunth. revealed carvacrol (41.51%), p-cymene (18.36%), γ-terpinene (17.03%) and thymol (4.86%) as major constituents, and the essential oil from Mentha spicata L. contained piperitona (81.18%), piperitenone (14.57%) and limonene (1.47%) as the principal components. The essential oils and the standard exhibited dose-dependent antioxidant activities at the concentrations tested. The essential oils were shown to be potential agents in the integrated management of the aphid Myzus persicae Sulzer.

关键词： Antioxidant Activity Insecticidal Activity Lamiaceae Natural Products Verbenaceae

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