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1.
Mol Carcinog ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629425

RESUMO

Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.

2.
Mol Biol Rep ; 50(1): 193-201, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36319786

RESUMO

PURPOSE: Breast cancer is the most common malignancy in developed countries and the main cause of deaths in women worldwide. Lactoferrin (Lf) is an iron-binding protein constituted for a single polypeptide chain that is folded into two symmetrical lobes that bind Fe2+ or Fe3+. Lf has the ability to reversibly bind Fe3+ and is found free of Fe3+ (Apo-Lf) or associated with Fe3+ (Holo-Lf) with a different three-dimensional conformation. However, the role of bovine Apo-Lf (Apo-BLf) and bovine Holo-Lf (Holo-BLf) in the migration and invasion induced by linoleic acid (LA) and fetal bovine serum (FBS), as well as in the expression of mesenchymal and epithelial proteins in breast cancer cells has not been studied. METHODS AND RESULTS: Scratch wound assays demonstrated that Holo-BLf and Apo-BLf do not induce migration, however they differentially inhibit the migration induced by FBS and LA in breast cancer cells MDA-MB-231. Western blot, invasion, zymography and immunofluorescence confocal microscopy assays demonstrated that Holo-BLf partly inhibit the invasion, FAK phosphorylation at tyrosine (Tyr)-397 and MMP-9 secretion, whereas it increased the number and size of focal adhesions induced by FBS in MDA-MB-231 cells. Moreover, Holo-BLf induced a slight increase of E-cadherin expression in MCF-7 cells, and inhibited vimentin expression in MCF-7 and MDA-MB-231 breast cancer cells. CONCLUSION: Holo-BLf inhibits cellular processes that mediate the invasion process in breast cancer cells.


Assuntos
Neoplasias da Mama , Lactoferrina , Humanos , Feminino , Lactoferrina/farmacologia , Lactoferrina/metabolismo , Neoplasias da Mama/metabolismo , Células MCF-7 , Células MDA-MB-231
3.
J Membr Biol ; 256(1): 79-90, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35751654

RESUMO

Caveolae are small plasma membrane invaginations constituted for membrane proteins namely caveolins and cytosolic proteins termed cavins, which can occupy up to 50% of the surface of mammalian cells. The caveolae have been involved with a variety of cellular processes including regulation of cellular signaling. Insulin is a hormone that mediates a variety of physiological processes through activation of insulin receptor (IR), which is a tyrosine kinase receptor expressed in all mammalian tissues. Insulin induces activation of signal transducers and activators of transcription (STAT) family members including STAT5. In this study, we demonstrate, for the first time, that insulin induces phosphorylation of STAT5 at tyrosine-694 (STAT5-Tyr(P)694), STAT5 nuclear accumulation and an increase in STAT5-DNA complex formation in MCF-7 breast cancer cells. Insulin also induces nuclear accumulation of STAT5-Tyr(P)694, caveolin-1, and IR in MCF-7 cells. STAT5 nuclear accumulation and the increase of STAT5-DNA complex formation require the integrity of caveolae and microtubule network. Moreover, insulin induces an increase and nuclear accumulation of STAT5-Tyr(P)694 in MDA-MB-231 breast cancer cells. In conclusion, results demonstrate that caveolae and microtubule network play an important role in STAT5-Tyr(P)694, STAT5 nuclear accumulation and STAT5-DNA complex formation induced by insulin in breast cancer cells.


Assuntos
Neoplasias da Mama , Cavéolas , Animais , Humanos , Feminino , Cavéolas/metabolismo , Insulina/farmacologia , Insulina/metabolismo , Células MCF-7 , Fator de Transcrição STAT5/metabolismo , Neoplasias da Mama/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Fosforilação , Tirosina/metabolismo , DNA/metabolismo , Mamíferos/metabolismo
4.
BMC Public Health ; 22(1): 2171, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36434586

RESUMO

BACKGROUND: Sex education programmes conducted by health professionals and educators are essential for young people to adopt healthy habits and attitudes towards their sexuality. The Forma Joven Program, promoted by the Andalusian Regional Government's Ministry of Health and Families and Education, is a good example of this. The aim of the study is to determine if different "degrees of intervention" in the informative consultancies of the Forma Joven Program imply differences in knowledge and attitudes towards sexuality. METHODS: This descriptive observational study analysed 27 Compulsory Secondary Education high schools in Huelva. These were included in the Program and belonged to a Primary Care Health District. Out of the 17 institutes initially selected because they met the inclusion criteria (4.256 students), finally 14 (3.596 students) participated. During the 2018/2019 school year, students from 3rd, 4th year of Secondary Compulsory Education (ESO), 1st, and 2nd Baccalaureate of the selected centres were asked to fill in a questionnaire of knowledge and attitudes towards sexuality. It collected variables such as age, sex, school year, institute, educational level and employment status of the father or mother and profile of the professional who delivers the counselling. RESULTS: A total of 1.237 students completed the questionnaire, which represents a participation rate of 34.4%. The average age was 15.59 years (SD 1.26) and 39.9% were girls. In some evaluated questions, we found statistically significant differences between the groups with different levels of exposure to counselling and the acquisition of knowledge and attitudes towards students' sexuality, although in most of them no such differences were found. The results of this study suggest the importance of the quality of counselling over quantity. Some classic myths persist in relation to sexuality and in some situations, they can be decisive when adopting preventive measures to avoid risks related to pregnancy and contagion of STIs. CONCLUSIONS: A greater number of counselling sessions does not imply acquiring a higher level of knowledge or better attitudes towards sexuality. Perhaps the quality of the education is more important than the quantity of counselling sessions.


Assuntos
Educação Sexual , Estudantes , Feminino , Gravidez , Humanos , Adolescente , Masculino , Comportamento Sexual , Sexualidade , Instituições Acadêmicas
5.
Technol Cancer Res Treat ; 21: 15330338221131647, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36222020

RESUMO

Breast cancer is the leading cause of cancer death among women worldwide. In solid tumors, the microenvironment plays a critical role in tumor development, and it has been described a communication between the different cell types that conform the stroma, including fibroblasts, pericytes, adipocytes, immune cells and cancer-associated fibroblasts. Intercellular communication is bidirectional, complex, multifactorial and is mediated by the secretion of molecules and extracellular vesicles. The extracellular vesicles are vesicles limited by two membranes that are secreted by normal and cancer cells into the extracellular space. Extracellular vesicle cargo is complex and includes proteins, miRNAs, DNA and lipids, and their composition is specific to their parent cells. Extracellular vesicles are taken up for neighboring or distant cells. Particularly, extracellular vesicles from breast cancer cells are taken up for fibroblasts and it induces the activation of fibroblasts into cancer-associated fibroblasts. Interestingly, cancer associated fibroblasts release extracellular vesicles that are taken up for breast cancer cells and promote migration, invasion, proliferation, epithelial-mesenchymal transition, changes in metabolism, chemoresistance, evasion of immune system and remodeling of extracellular matrix. In addition, the enrichment of specific cargos in extracellular vesicles of breast cancer patients has been suggested to be used as biomarkers of the disease. Here we review the current literature about the intercommunication between tumor cells and cancer associated fibroblasts through extracellular vesicles in breast cancer.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Vesículas Extracelulares , MicroRNAs , Biomarcadores , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/metabolismo , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Lipídeos , MicroRNAs/genética , MicroRNAs/metabolismo , Microambiente Tumoral
6.
Adv Clin Exp Med ; 31(12): 1309-1318, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36047897

RESUMO

BACKGROUND: The assessment of motor function is vital in post-stroke rehabilitation protocols, and it is imperative to obtain an objective and quantitative measurement of motor function. There are some innovative machine learning algorithms that can be applied in order to automate the assessment of upper extremity motor function. OBJECTIVES: To perform a systematic review and meta-analysis of the efficacy of machine learning algorithms for assessing upper limb motor function in post-stroke patients and compare these algorithms to clinical assessment. MATERIAL AND METHODS: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database. The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed using 6 electronic databases. The meta-analysis was performed with the data from the correlation coefficients using a random model. RESULTS: The initial search yielded 1626 records, but only 8 studies fully met the eligibility criteria. The studies reported strong and very strong correlations between the algorithms tested and clinical assessment. The meta-analysis revealed a lack of homogeneity (I2 = 85.29%, Q = 48.15), which is attributable to the heterogeneity of the included studies. CONCLUSION: Automated systems using machine learning algorithms could support therapists in assessing upper extremity motor function in post-stroke patients. However, to draw more robust conclusions, methodological designs that minimize the risk of bias and increase the quality of the methodology of future studies are required.


Assuntos
Transtornos Motores , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Extremidade Superior , Reabilitação do Acidente Vascular Cerebral/métodos , Paresia
7.
Int J Equity Health ; 21(1): 112, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978319

RESUMO

BACKGROUND: The significant increase in access to oncological medicines through court cases suggests that constitutional guarantees of integral and universal care in the Brazilian public health system are uncertain. METHODS: A retrospective observational study was conducted to analyze data from lawsuits requesting oncological medicines from 2014 to 2020 in the State of Goiás, Brazil, in state and federal courts. Sociodemographic, medical, and legal variables were statistically examined using descriptive, association, and correlation methods. RESULTS: Women brought more than half (54%) of the 301 processes analyzed. The most frequent age group was over 55 years, with income below 3 × the minimum wage (total about USD$600/month), and their cases were promoted through the public minister and public defender's offices. The most requested medications, not on official public health system lists, were indicated for multiple myeloma and brain cancer. CONCLUSIONS: Improved quality of life, frequently used as a justification, could be conceptually confused with increased survival. Finally, judicialization itself indicates that individual health needs arise even with properly defined and adequately implemented public policies. These needs should be considered for the adequate provisioning of services by the state to ensure the right to health.


Assuntos
Medicamentos Essenciais , Política de Saúde , Brasil , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Qualidade de Vida
8.
Tissue Cell ; 76: 101814, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35526310

RESUMO

Breast cancer is the most frequent malignancy among women in developed countries and the main cause of death related to cancer in women worldwide. Extracellular vesicles (EVs) are vesicles with a variable size enclosed within a phospholipid bilayer that contain a variety of molecules with biological activity. Cancer cells release EVs that induce proliferation, escape from apoptosis, reprogramming energy metabolism, invasion and metastasis. In this study we studied whether EV fractions deprived of platelet EVs from breast cancer women (BC EVs) can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that BC EVs enhance migration, invasion and formation of new tubules in HUVECs, compared with EV fractions deprived of platelet EVs from healthy women (Ctrl EVs). In summary, we demonstrate, for the first time, that BC EVs induce cellular processes in HUVECs that participate in angiogenesis.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Neoplasias da Mama/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Neovascularização Patológica/patologia
9.
J Cell Commun Signal ; 16(4): 531-546, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34309795

RESUMO

Insulin-like growth factor-1 (IGF-1) plays an important role in function and development of the mammary gland. However, high levels of IGF-1 has been associated with an increased risk of breast cancer development. Epithelial-mesenchymal transition (EMT) is a process where epithelial cells lose their epithelial characteristics and acquire a mesenchymal phenotype, which is considered one of the most important mechanisms in cancer initiation and promotion of metastasis. Extracellular vesicles (EVs) are released into the extracellular space by different cell types, which mediate intercellular communication and play an important role in different physiological and pathological processes, such as cancer. In this study, we demonstrate that EVs from MDA-MB-231 breast cancer cells stimulated with IGF-1 (IGF-1 EVs) decrease the levels of E-cadherin, increase the expression of vimentin and N-cadherin and stimulate the secretion of metalloproteinase-9 in mammary non-tumorigenic epithelial cells MCF10A. IGF-1 EVs also induce the expression of Snail1, Twist1 and Sip1, which are transcription factors involved in EMT. Moreover, IGF-1 EVs induce activation of ERK1/2, Akt1 and Akt2, migration and invasion. In summary, we demonstrate, for the first time, that IGF-1 EVs induce an EMT process in mammary non-tumorigenic epithelial cells MCF10A.

10.
Brain Inj ; 35(7): 842-849, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33678100

RESUMO

Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests.Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.


Assuntos
Lesões Encefálicas Traumáticas , Prótons , Coagulação Sanguínea , Lesões Encefálicas Traumáticas/complicações , Humanos , Simulação de Dinâmica Molecular
11.
Med Oncol ; 38(4): 40, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33728516

RESUMO

Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in occidental diets, which mediate a variety of processes in human breast cancer cells, including migration and invasion. Extracellular vesicles (EVs) are vesicles released from endosomes and plasma membrane that are composed of a variety of molecules, including proteins, nucleic acids and lipids. EVs from cancer cells promote processes related with cancer progression. In the present study, we demonstrate that treatment of MDA-MB-231 cells with EVs from MDA-MB-231 cells stimulated with LA (LA EVs) promote migration and invasion via Src activity. LA EVs induce activation of FAK via Src activity and of Src and Akt2. LA EVs also induce the assembly of focal adhesions and MMP-9 secretion. These findings demonstrate that LA EVs mediate an autocrine and/or paracrine Src/FAK signaling pathway to promote migration and invasion.


Assuntos
Movimento Celular/efeitos dos fármacos , Vesículas Extracelulares/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Ácido Linoleico/farmacologia , Quinases da Família src/metabolismo , Linhagem Celular Tumoral , Vesículas Extracelulares/efeitos dos fármacos , Adesões Focais/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Prostaglandins Other Lipid Mediat ; 153: 106519, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33238201

RESUMO

Extracellular vesicles (EVs) are vesicles secreted by normal and malignant cells that are implicated in tumor progression. Linoleic acid (LA) is an essential polyunsaturated fatty acid that induces migration, invasion and an increase in phospholipase D activity in breast cancer cells. In this study, we determined whether stimulation of MDA-MB-231 breast cancer cells with LA induces the secretion of EVs, which can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that treatment of MDA-MB-231 cells with 90 µM LA for 48 h induce an increase in the number of EVs released. Moreover, EVs from MDA-MB-231 stimulated with 90 µM LA induce FAK and Src activation and migration via FAK and Src activity, whereas the secretion of these EVs is through FFAR1 and FFAR4 activation in HUVECs. The EVs from MDA-MB-231 cells treated with LA also increase proliferation, invasion, MMP-9 secretion, an increase of MMP-2 secretion and formation of new tubules in HUVECs. In summary, we demonstrate, for the first time, that treatment with LA induces the release of EVs from MDA-MB-231 cells that induce cellular processes involved with angiogenesis in HUVECs.


Assuntos
Células Endoteliais da Veia Umbilical Humana , Neoplasias da Mama , Humanos , Ácido Linoleico , Metaloproteinase 2 da Matriz
13.
Med Hypotheses ; 144: 110296, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254487

RESUMO

The factors that may contribute to a COVID-19 patient remaining in the asymptomatic stage, or to the infection evolving into the more serious stages are examined. In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2. Also, we review other factors related to the susceptibility and pathogenicity of SARS-CoV-2.


Assuntos
Infecções Assintomáticas , COVID-19/genética , Predisposição Genética para Doença , SARS-CoV-2 , Serina Endopeptidases/genética , Alelos , Androgênios/metabolismo , Enzima de Conversão de Angiotensina 2/genética , COVID-19/virologia , RNA-Polimerase RNA-Dependente de Coronavírus , Exoma , Feminino , Perfilação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Modelos Teóricos , Mutação , Fases de Leitura Aberta , Polimorfismo de Nucleotídeo Único , Proteínas não Estruturais Virais/genética , Vitamina D/análogos & derivados , Vitamina D/metabolismo
14.
Romina Libster; Gonzalo Perez Marc; Diego Wappner; Silvina Coviello; Alejandra Bianchi; Virginia Braem; Ignacio Esteban; Mauricio Tomas Caballero; Cristian J Wood; Mabel Berrueta; Anibal Rondan; Gabriela Lescano; Pablo Cruz; Ivonne Ritou; Valeria Fernandez Vina; Damian Alvarez Paggi; Sebastian Esperante; Adrian Ferretti; Gaston Ofman; Alvaro Ciganda; Rocio Rodriguez; Jorge Lantos; Ricardo Valentini; Nicolas Itcovici; Alejandra Hintze; Laura Oyarvide; Candela Etchegaray; Alejandra Neira; Ivonne Name; Julieta Alfonso; Rocio Lopez Castelo; Gisela Caruso; Sofia Rapelius; Fernando Alvez; Federico Cesar Etchenique; Federico Dimase; Dario Raul Alvarez; Sofia Sol Aranda; Clara Sanchez Yanotti; Julian DeLuca; Sofia Jarez Baglivo; Sofia Lujan Laudanno; Florencia Nowogrodzki; Florencia Izetta; Maria Teresa Paniguetti; Paula Fernandez Estrella; Maria Emilia Gutierrez Meyer; Viviana Dominguez; Marcela Balduzzi; Romina Militerno; Jimena Ochoa; Sebastian Perez Marc; Lucila DiNunzio; Mariano Aizpurua; Romina Zadoff; Carla Marchionatti; Natalia Garcia Escude; Romina Romero; Noelia Iraizos; Emmanuel Ezequiel Valls; Patricia Rearte Carvalho; Jimena Franco; Natali Estrada; Juan Rusconi; Guido Ochoa; Maria Veronica Paz; Patricia Lesch; Maria Fernanda Caracciolo; Maria Eugenia Macaneo; Lia Pocket; Silvana Marquez; Gaston Pellegrino; Jorge Geffner; Rocio Zarlenga; Camila Witteveen; Agustina Venditti; Indira Pichetto Olanda; Juan Mauricio Vargas; Micaela Piani; Daniela Carolina Galnarez; Florencia De la Fuente; Andrea Gamarnik; Maria del Carmen Nigro; Susana Villaroel; Cristina Soler Riera; Leonel Langellotti; Clarisa Taffarel; Jose L Scapellato; Mariano Girasolli; Maximiliano de Zan; Juan Sebastian Riera; Enio Garcia; Mario Rovere; Juan Canela; Agostina Pagella; Cecilia Pampuro; Yanina Miragaya; Silvina Kuperman; Alfonso Raggio; Ramiro Manuel Larrea; Maria Dolores Silveyra; Gabriela Leberzstein; Alejandra Debonis; Juan Molinos; Miguel Gonzalez; Eduardo Perez; Nicolas Kreplak; Susana Pastor Arguello; Luz Gibbons; Fernando Althabe; Eduardo Bergel; Fernando P Polack.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20234013

RESUMO

BackgroundTherapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced plasma infusions to the first 72 hours of symptoms to arrest COVID-19 progression. MethodsA randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against SARS-CoV2 in elderly subjects within 72 hours of mild COVID-19 symptoms. The primary endpoint was severe respiratory disease defined as a respiratory rate [≥]30 and/or an O2 sat<93% in room air. The study was interrupted at 76% of its projected sample size, because cases in the region decreased considerably and steady enrollment of study subjects became virtually impossible. Results160 patients underwent randomization. In the intention-to-treat analysis (ITT), 13/80(16.2%) patients receiving plasma vs. 25/80(31.2%) receiving placebo experienced severe respiratory disease [RR(95%CI)= 0.52(0.29,0.94); p=0.026)] with an RRR=48%. A modified ITT analysis, excluding six subjects who experienced the primary endpoint before infusion, showed a larger effect size [RR(95%CI) = 0.40(0.20, 0.81), p=0.007]. High- and low-titer donor analyses, based on a median IgG titer=1:3,200, evidenced a dose-dependent response with an RRR=73.3% for recipients of high-titer plasma (p=0.016) and a number needed to treat (NNT)=4.4. All secondary endpoints exhibited trends towards protection. No solicited adverse events were observed. ConclusionsEarly administration of high-titer convalescent plasma against SARS-CoV2 to mildly ill infected seniors reduced COVID-19 progression. This safe, inexpensive, outpatient intervention facilitates access to treatment from industrialized to LMIC, can decompress demands on hospitals, and may contribute to save lives. Funded by The Bill & Melinda Gates Foundation and The Fundacion INFANT Pandemic Fund. Registered in the Direccion de Sangre y Medicina Transfusional del Ministerio de Salud (PAEPCC19), Plataforma PRIISA (1421), and clinicaltrials.gov (NCT04479163). All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organization for the submitted work; RL, GPM, DW and FPP are investigators in a phase 3 SARS CoV2 trial from Pfizer; no other relationships or activities that could appear to have influenced the submitted work.

15.
Toxicol In Vitro ; 66: 104871, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32325111

RESUMO

Bisphenol A (BPA) is an industrial synthetic chemical used in the production of polycarbonate plastics and epoxy resins. Human exposition to BPA is primarily through eating food, and drinking liquids, because BPA can leach from polycarbonate plastic containers, beverage cans and epoxy resins. BPA induces proliferation and migration in human breast cancer cells. The G protein-coupled estrogen receptor (GPER) is a G protein-coupled receptor coupled with Gs proteins that is activated by estrogen and estrogenic compounds and it is the receptor for BPA. However, the signal transduction pathways that mediate migration via BPA/GPER in triple negative breast cancer (TNBC) cells has not been studied in detail. Here, we demonstrate that BPA induces an increase of GPER expression and activation of FAK, Src and ERK2, and an increase of focal adhesion assembly via GPER in TNBC MDA-MB-231 cells. Moreover, BPA induces FAK and ERK2 activation, focal adhesion assembly and migration via epidermal growth factor receptor (EGFR) transactivation. Collectively our data showed that BPA via GPER and/or EGFR transactivation induces activation of signal transduction pathways that mediate migration in TNBC MDA-MB-231 cells.


Assuntos
Compostos Benzidrílicos/toxicidade , Adesões Focais/efeitos dos fármacos , Fenóis/toxicidade , Plastificantes/toxicidade , Proteínas Tirosina Quinases/metabolismo , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética
16.
Indian J Med Res ; 151(1): 11-21, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32134010

RESUMO

Obesity is a serious medical condition worldwide, which needs new approaches and recognized international consensus in treating diseases leading to morbidity. The aim of this review was to examine heterogeneous links among the various phenotypes of obesity in adults. Proteins and associated genes in each group were analysed to differentiate between biomarkers. A variety of terms for classification and characterization within this pathology are currently in use; however, there is no clear consensus in terminology. The most significant groups reviewed include metabolically healthy obese, metabolically abnormal obese, metabolically abnormal, normal weight and sarcopenic obese. These phenotypes do not define particular genotypes or epigenetic gene regulation, or proteins related to inflammation. There are many other genes linked to obesity, though the value of screening all of those for diagnosis has low predictive results, as there are no significant biomarkers. It is important to establish a consensus in the terminology used and the characteristics attributed to obesity subtypes. The identification of specific molecular biomarkers is also required for better diagnosis in subtypes of obesity.


Assuntos
Biomarcadores , Obesidade/diagnóstico , Obesidade/genética , Proteínas/genética , Adulto , Genótipo , Humanos , Obesidade/classificação , Obesidade/epidemiologia , Fenótipo
17.
J Cell Commun Signal ; 13(2): 235-244, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30361980

RESUMO

In breast cancer cells, the linoleic acid (LA), an ω-6 essential polyunsaturated fatty acid, induces a variety of biological processes, including migration and invasion. Extracellular vesicles (EVs) are structures released by normal and malignant cells into extracellular space, and their function is dependent on their cargo and the cell type from which are secreted. Particularly, the EVs from MDA-MB-231 breast cancer cells treated with LA promote an epithelial-mesenchymal-transition (EMT)-like process in mammary non-tumorigenic epithelial cells MCF10A. Here, we found that EVs isolated from supernatants of MDA-MB-231 breast cancer cells stimulated with 90 µM LA induces activation of Akt2, FAK and ERK1/2 in MCF10A cells. In addition, EVs induces migration through a PI3K, Akt and ERK1/2-dependent pathway, whereas invasion is dependent on PI3K activity.

18.
Cien Saude Colet ; 23(4): 1089-1096, 2018 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29694595

RESUMO

The aim of this study was to assess the presence of suicidal ideation and depressive symptoms among adolescents in Chiapas, Mexico based on predictor variables. A cross-sectional study adopting an ex post facto design was conducted with a non-probability sample of 4,759 students of both sexes with an average age of 18.4 years and using the following tools: the Center for Epidemiologic Studies Depression Scale, Roberts' Suicidal Ideation Scale, the Impulsiveness Scale (IS), and the Rosenberg Self-Esteem Scale. The mean score obtained by the suicidal ideation scale was 0.2, which is lower than that reported by other studies, while the mean score for depressive symptoms was similar to those in the literature. The prevalence of suicidal ideation was 7.8%, which is lower than reported in national and international studies. Multivariable logistic regression showed that impulsiveness (OR = 1.907) and depressive symptoms (OR = 9.006) lead to a twofold and ninefold increase in the likelihood of suicidal ideation, respectively. The findings also showed a strong association between suicidal ideation and depressive symptoms, showing that the latter is a predictor of suicidal ideation among adolescents.


Assuntos
Depressão/epidemiologia , Comportamento Impulsivo , Estudantes/estatística & dados numéricos , Ideação Suicida , Adolescente , Estudos Transversais , Feminino , Humanos , Funções Verossimilhança , Modelos Logísticos , Masculino , México/epidemiologia , Prevalência , Escalas de Graduação Psiquiátrica , Autoimagem , Estudantes/psicologia , Adulto Jovem
19.
Ciênc. Saúde Colet. (Impr.) ; 23(4): 1089-1096, abr. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-952643

RESUMO

Resumen El objetivo del trabajo es evaluar la presencia de ideación suicida y sintomatología depresiva a partir de variables predictoras en adolescentes de Chiapas, México. El estudio es de tipo transversal, ex post-facto. Se aplicaron las escalas de Ideación Suicida, de Depresión del Centro de Estudios Epidemiológicos, Impulsividad y Autoestima, a una muestra no probabilística de 4,759 estudiantes de ambos sexos, con una edad promedio de 18.4 años. Los resultados indican que el puntaje de media para la ideación suicida (0.2), es inferior a lo reportado en otros estudios, mientras que para sintomatología depresiva, es similar. La prevalencia de ideación suicida es del 7.8%, por debajo de los índices señalados en el ámbito nacional e internacional. Los modelos de regresión logística multivariable para ideación suicida, confirman que la impulsividad y sintomatología depresiva, la hacen aumentar a casi el doble (OR= 1.907) y nueve veces (OR= 9.006) respectivamente. Es evidente la estrecha relación entre la ideación suicida y la sintomatología depresiva, señalándose la relevancia que esta tiene como predictora de su presencia en población adolescente.


Abstract The aim of this study was to assess the presence of suicidal ideation and depressive symptoms among adolescents in Chiapas, Mexico based on predictor variables. A cross-sectional study adopting an ex post facto design was conducted with a non-probability sample of 4,759 students of both sexes with an average age of 18.4 years and using the following tools: the Center for Epidemiologic Studies Depression Scale, Roberts' Suicidal Ideation Scale, the Impulsiveness Scale (IS), and the Rosenberg Self-Esteem Scale. The mean score obtained by the suicidal ideation scale was 0.2, which is lower than that reported by other studies, while the mean score for depressive symptoms was similar to those in the literature. The prevalence of suicidal ideation was 7.8%, which is lower than reported in national and international studies. Multivariable logistic regression showed that impulsiveness (OR = 1.907) and depressive symptoms (OR = 9.006) lead to a twofold and ninefold increase in the likelihood of suicidal ideation, respectively. The findings also showed a strong association between suicidal ideation and depressive symptoms, showing that the latter is a predictor of suicidal ideation among adolescents.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Idoso , Estudantes/estatística & dados numéricos , Depressão/epidemiologia , Ideação Suicida , Comportamento Impulsivo , Escalas de Graduação Psiquiátrica , Autoimagem , Estudantes/psicologia , Funções Verossimilhança , Modelos Logísticos , Prevalência , Estudos Transversais , México/epidemiologia
20.
Trop Biomed ; 35(3): 678-683, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601755

RESUMO

The chronic indeterminate phase of Chagas' disease is asymptomatic despite positive test results for antibodies specific to Trypanosoma cruzi. CD62P-APC (P-selectin) and PAC-1 FITC (GpIIb/IIIa) may improve diagnosis as biomarkers of platelet activity. Nine asymptomatic seropositive subjects, previously untreated, were selected from a blood bank within a year of Chagas' disease detection, in addition to a control group of four. All subjects were evaluated by flow cytometry for CD62P, PAC-1 and CD41, and in a complementary study, by Tissue Doppler Echocardiography for isovolumic relaxation times (IVRT) and E/A ratios. The subjects were classified as positive or negative for CD62P and PAC-1 by a cut off obtained from their mean±2SD. For IVRT and E/A ratios, cut offs were obtained from the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations. Fisher's exact test was used for associated findings. Pre-test and post-test probability, sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Abnormalities were expressed as platelet hyperactivity and ventricular dysfunction in CD62P, PAC-1, IVRT and E/A ratios. CD62P appears to have greater sensitivity (0.75) and PAC-1, more accurate specificity (0.75), which may explain thrombotic events in Chagas' disease. We recommend the use of CD62P and PAC-1 as biomarkers of platelet hyperactivity in patients in the chronic indeterminate phase of Chagas' disease.

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