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1.
Proc Natl Acad Sci U S A ; 120(33): e2302661120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549288

RESUMO

Polycystic Echinococcosis (PE), a neglected life-threatening zoonotic disease caused by the cestode Echinococcus vogeli, is endemic in the Amazon. Despite being treatable, PE reaches a case fatality rate of around 29% due to late or missed diagnosis. PE is sustained in Pan-Amazonia by a complex sylvatic cycle. The hunting of its infected intermediate hosts (especially the lowland paca Cuniculus paca) enables the disease to further transmit to humans, when their viscera are improperly handled. In this study, we compiled a unique dataset of host occurrences (~86000 records) and disease infections (~400 cases) covering the entire Pan-Amazonia and employed different modeling and statistical tools to unveil the spatial distribution of PE's key animal hosts. Subsequently, we derived a set of ecological, environmental, climatic, and hunting covariates that potentially act as transmission risk factors and used them as predictors of two independent Maximum Entropy models, one for animal infections and one for human infections. Our findings indicate that temperature stability promotes the sylvatic circulation of the disease. Additionally, we show how El Niño-Southern Oscillation (ENSO) extreme events disrupt hunting patterns throughout Pan-Amazonia, ultimately affecting the probability of spillover. In a scenario where climate extremes are projected to intensify, climate change at regional level appears to be indirectly driving the spillover of E. vogeli. These results hold substantial implications for a wide range of zoonoses acquired at the wildlife-human interface for which transmission is related to the manipulation and consumption of wild meat, underscoring the pressing need for enhanced awareness and intervention strategies.


Assuntos
Equinococose , Echinococcus , Animais , Humanos , Hotspot de Doença , Equinococose/epidemiologia , Zoonoses/epidemiologia , Fatores de Risco , El Niño Oscilação Sul
2.
EMBO Rep ; 22(5): e50781, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655623

RESUMO

Treatment of triple-negative breast cancer (TNBC) remains challenging due to a lack of effective targeted therapies. Dysregulated glucose uptake and metabolism are essential for TNBC growth. Identifying the molecular drivers and mechanisms underlying the metabolic vulnerability of TNBC is key to exploiting dysregulated cancer metabolism for therapeutic applications. Mitogen-inducible gene-6 (MIG-6) has long been thought of as a feedback inhibitor that targets activated EGFR and suppresses the growth of tumors driven by constitutive activated mutant EGFR. Here, our bioinformatics and histological analyses uncover that MIG-6 is upregulated in TNBC and that MIG-6 upregulation is positively correlated with poorer clinical outcomes in TNBC. Metabolic arrays and functional assays reveal that MIG-6 drives glucose metabolism reprogramming toward glycolysis. Mechanistically, MIG-6 recruits HAUSP deubiquitinase for stabilizing HIF1α protein expression and the subsequent upregulation of GLUT1 and other HIF1α-regulated glycolytic genes, substantiating the comprehensive regulation of MIG-6 in glucose metabolism. Moreover, our mouse studies demonstrate that MIG-6 regulates GLUT1 expression in tumors and subsequent tumor growth in vivo. Collectively, this work reveals that MIG-6 is a novel prognosis biomarker, metabolism regulator, and molecular driver of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glucose , Glicólise/genética , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/genética , Proteínas Supressoras de Tumor/genética
3.
An Acad Bras Cienc ; 95(suppl 1): e20220502, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255169

RESUMO

Healthcare workers present an increased risk of contagion for the SARS-CoV-2 virus due to their labor exposure. Here, we describe the clinical, laboratory, and immunological characteristics of healthcare workers, before vaccine application, exposed to SARS-CoV-2-infected patients. We collected sociodemographic, clinical, and laboratory information from 50 professionals who worked during the COVID-19 pandemic at the Clinical Hospital of the Northwest in Brazil. The results showed that most workers are women, over 50 years old, and worked as nursing technicians. Approximately 56% of workers were positive for a previous infection by RT-PCR and/or anti-SARS-CoV-2-immunoglobulin tests. Increased levels of hematocrit, neutrophils, NK lymphocytes, and fibrinogen, were found in positive healthcare workers, suggesting a light inflammatory status. The immunological findings showed an increase in IL-17 production and a Th2/Th17/Th22 profile followed by high serology for anti-SARS-CoV-2 IgM and IgG. Those data reveal the importance of studies with healthcare workers to investigate if the continuous exposition to the virus may result in chronic activation of the immune system and/or pulmonary inflammation in this target group.


Assuntos
COVID-19 , Vacinas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , COVID-19/prevenção & controle , SARS-CoV-2 , Brasil , Pandemias , Pessoal de Saúde
4.
Int J Sports Med ; 44(8): 584-591, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37146639

RESUMO

The aim of this study was to compare the effects of continuous-moderate vs. high-intensity interval aerobic training on cardiovascular and metabolic parameters in ovariectomized high-fat-fed mice. C57BL/6 female ovariectomized were divided into four groups (n=8): low-fat-fed sedentary (SLF); high-fat-fed sedentary (SHF); high-fat-fed moderate-intensity continuous trained (MICT-HF); and high-fat-fed high-intensity interval aerobic trained (HIIT-HF). The high-fat diet lasted 10 weeks. Ovariectomy was performed in the fourth week. The exercise training was carried out in the last four weeks of protocol. Fasting glycemia, oral glucose tolerance, arterial pressure, baroreflex sensitivity, and cardiovascular autonomic modulation were evaluated. Moderate-intensity continuous training prevented the increase in arterial pressure and promoted a reduction in HR at rest, associated with an improvement in the sympathovagal balance in MICT-HF vs. SHF. The high-intensity interval training reduced blood glucose and glucose intolerance in HIIT-HF vs. SHF and MICT-HF. In addition, it improved sympathovagal balance in HIIT-HF vs. SHF. Moderate-intensity continuous training was more effective in promoting cardiovascular benefits, while high-intensity interval training was more effective in promoting metabolic benefits.


Assuntos
Doenças Cardiovasculares , Treinamento Intervalado de Alta Intensidade , Camundongos , Animais , Feminino , Camundongos Obesos , Camundongos Endogâmicos C57BL , Glicemia/metabolismo , Coração , Treinamento Intervalado de Alta Intensidade/métodos
5.
BMC Vet Res ; 18(1): 223, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698226

RESUMO

BACKGROUND: Five hundred 8-d old male broilers Cobb500 were randomly allotted into 10 treatments in factorial arrangement with 5 Cu levels (0, 4, 8, 12, and 16 mg/kg), and 2 sources (Cu proteinate, CuPro and Cu sulphate, CuSO4.5H2O) for a 10-d-experiment. RESULTS: Feed conversion ratio (FCR) was better (P < 0.05) in CuPro fed chicks compared with CuSO4.5H2O group. Average daily feed intake (ADFI) decreased linearly (P < 0.05) as dietary Cu increased. A quadratic response (P < 0.05) to Cu levels was found for FCR, being optimized at 9.87 and 8.84 mg Cu/kg in CuPro and CuSO4.5H2O diets, respectively. Copper supplementation linearly increased liver Cu content (P < 0.05) and tended to linearly increase (P = 0.07) phosphorus (P) and copper in tibia. Manganese and zinc were higher (P < 0.05) in tibia of CuPro fed birds. Broilers fed CuPro exhibited lower liver iron (P < 0.05) content, lower activities of Cu, Zn superoxide dismutase (CuZnSOD) in breast muscle and liver, and glutathione peroxidase in liver. Glutathione peroxidase reduced linearly (P < 0.05) with CuPro levels and increased linearly (P < 0.05) with CuSO4.5H2O levels and were lower (P < 0.05) in all CuPro levels in breast muscle. Breast muscle malondialdehyde concentration tended to be higher (P = 0.08) in broilers fed CuSO4.5H2O. Copper levels linearly increased (P < 0.05) metallothionein (MT) and malate dehydrogenase (MDH) expression in liver, and six-transmembrane epithelial antigen of the prostate-1 (STEAP-1) in the intestine. Copper elicited a quadratic response (P < 0.050) in AKT-1 and mammalian target of rapamycin (mTOR) in breast muscle, CuZnSOD in liver and antioxidant 1 copper chaperone (ATOX 1) in intestine. Broilers fed CuPro exhibited higher mRNA expression of mTOR in muscle breast and lower CuZnSOD in liver and ATOX 1 in intestine. Interaction (P < 0.05) between levels and sources was found in mRNA expression for GSK-3ß, MT, and CuZnSOD in breast muscle, FAS and LPL in liver and MT and CTR1 in intestine. CONCLUSIONS: CuPro showed beneficial effects on feed conversion and bone mineralization. Organic and inorganic Cu requirements are 9.87 and 8.84 mg Cu/kg, respectively.


Assuntos
Galinhas , Cobre , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Cobre/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Glutationa Peroxidase , Glicogênio Sintase Quinase 3 beta , Lipídeos , Masculino , Mamíferos , Minerais , RNA Mensageiro , Superóxido Dismutase , Serina-Treonina Quinases TOR
6.
Adv Exp Med Biol ; 1373: 329-339, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35612806

RESUMO

AIM: to provide an update of the evidence on the effect of oral hygiene instructions (OHI), dental plaque control and in the prevention and treatment of periodontitis. METHODS: Literature searches were performed using MeSH terms, keywords and free words and were published between 2015 and November 2020. The data from the articles were summarized in a narrative review. RESULTS: Data concerning the influence of OHI on periodontal features, the impact of OHI before periodontitis non-surgical treatment, its efficacity on periodontitis prevention and maintenance of healthy periodontium were summarized in the tables of the present narrative review. CONCLUSION: as prevention is better than a cure, it is relevant to bring in light the role of oral hygiene instructions, the patient self-control of dental plaque as well as the professional mechanical plaque removal in the prevention of periodontitis.


Assuntos
Placa Dentária , Doenças Periodontais , Periodontite , Placa Dentária/prevenção & controle , Humanos , Higiene Bucal , Doenças Periodontais/prevenção & controle , Periodontite/prevenção & controle
7.
An Acad Bras Cienc ; 94(3): e20211590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35766602

RESUMO

Health professionals working to mitigate the COVID-19 pandemic are one of the main risk groups for the disease, being prioritized for vaccination. Considering this, the aim of this study was to analyze the immune response of these professionals immunized with CoronaVac in the first and second doses. Blood samples were collected after the first and second doses of the vaccine (CoronaVac) and used to investigate hematological and biochemical parameters, analysis of immunoglobulin production, cytokines, and gene expression profile, as well as the identification of subsets of immune cells. Post-first dose immunological phenotypic memory (CD27+) profiles (T CD4+, TCD8+ and CD19+) showed a significant increase, as did Monocyte APCs (CD80+HLA-DR+) in relation to the second dose. The cytokines IL-2, IL-6 and IFN-° showed increased values in relation to the other analyzed cytokines. The Th2/Th17 profile in the second dose was characterized by gene expression analysis. The production of IgM and IgG after vaccination showed statistically significant values in the comparison between doses. CoronaVac showed activation of APCs monocytes, memory response of T and B lymphocytes, with immunoglobulins production. This set of responses is characterized by the Th2/Th17 immunological profile.


Assuntos
Formação de Anticorpos , COVID-19 , COVID-19/prevenção & controle , Citocinas/metabolismo , Humanos , Pandemias , Linfócitos T , Vacinação , Vacinas de Produtos Inativados
8.
Cancer Causes Control ; 32(4): 327-336, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33447892

RESUMO

PURPOSE: Glioblastoma prognosis remains dismal despite gross total removal (GTR) followed by chemoradiotherapy. Other known prognostic factors include functional status, age and IDH mutation status. However, to improve patient outcome, a search for other features with impact on survival is needed. We aimed to analyse the impact of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) of surgically resected primary glioblastoma and evaluate if BMI constitutes an independent prognostic factor. METHODS: We analysed all adult glioblastoma patients who underwent surgery and chemoradiotherapy between 2011 and 2017 at our institution. Overall survival was the study-primary endpoint, and progression-free survival-the secondary endpoint. We assayed age, gender, histology, extent of resection, IDH, functional and smoking status, cardiovascular risk factors, BMI, OS and PFS. Univariate analysis was conducted followed by multivariate analysis to establish independent prognostic factors. In accordance with the World Health Organization (WHO) BMI stratification, survival curves were obtained for normal-weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (≥ 30 kg/m2) patient subgroups in addition to the non-obese (18.5-29.9 kg/m2) population. RESULTS: 193 patients were evaluated, with a median follow-up time of 17.3 months. Median OS was 21.3 months in obese patients vs 16.2 months in the non-obese (p = 0.017) and 16 months in the normal weight (p = 0.007). Higher median OS was also observed in patients under 60 and those in which GTR was obtained. Median PFS in obese individuals was 9 months in comparison to 6 months in the normal-weight subgroup (p = 0.04) and 7 months in the non-obese (p = 0.050). Multivariate analysis identified age < 60 (p = 0.044), GTR (p = 0.004) and BMI ≥ 30 (p = 0.009) as independent prognostic factors for increased overall survival. CONCLUSION: Higher BMI was associated with longer OS and PFS. Prospective studies are needed to validate these findings.


Assuntos
Índice de Massa Corporal , Neoplasias Encefálicas/mortalidade , Glioblastoma/mortalidade , Neoplasias Encefálicas/terapia , Feminino , Glioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
9.
Hum Reprod ; 36(11): 2916-2920, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34535998

RESUMO

Selective LH deficiency has been described in several men, but only in two women who presented normal pubertal development but secondary amenorrhoea due to anovulation. Despite its rarity, this condition represents a valuable model for studying the processes regulated by FSH or LH during late folliculogenesis and ovulation in humans. A woman previously diagnosed with selective LH deficiency due to a homozygous germline splice site mutation in LHB (IVS2 + 1G→C mutation) was submitted to an individualised ovarian induction protocol, first with recombinant LH and then with highly purified urinary hCG. Ovarian follicle growth and ovulation were achieved, and a healthy baby was born after an uneventful term pregnancy. The treatment described herein demonstrates that the clinical actions of exogenous LH or hCG in inducing late-stage follicular development in women with deficient LH production or performance might be interchangeable or inevitable, once FSH-dependent early follicular growth is assured.


Assuntos
Anovulação , Gonadotropina Coriônica , Feminino , Hormônio Foliculoestimulante , Humanos , Hormônio Luteinizante , Masculino , Ovulação , Indução da Ovulação , Gravidez
10.
Phys Chem Chem Phys ; 23(48): 27103-27123, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34859800

RESUMO

In this perspective review, we discuss the power of polarized Raman spectroscopy to study optically anisotropic 2D materials, belonging to the orthorhombic, monoclinic and triclinic crystal families. We start by showing that the polarization dependence of the peak intensities is described by the Raman tensor that is unique for each phonon mode, and then we discuss how to determine the tensor elements from the angle-resolved polarized measurements by analyzing the intensities in both the parallel- and cross-polarized scattering configurations. We present specific examples of orthorhombic black phosphorus and monoclinic 1T'-MoTe2, where the Raman tensors have null elements and their principal axes coincide with the crystallographic ones, followed by a discussion on the results for triclinic ReS2 and ReSe2, where the axes of the Raman tensor do not coincide with the crystallographic axes and all elements are non-zero. We show that the Raman tensor elements are, in general, given by complex numbers and that phase differences between tensor elements are needed to describe the experimental results. We discuss the dependence of the Raman tensors on the excitation laser energy and thickness of the sample within the framework of the quantum model for the Raman intensities. We show that the wavevector dependence of the electron-phonon interaction is essential for explaining the distinct Raman tensor for each phonon mode. Finally, we close with our concluding remarks and perspectives to be explored using angle-resolved polarized Raman spectroscopy in optically anisotropic 2D materials.

11.
Nano Lett ; 20(1): 284-291, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31794217

RESUMO

One-dimensional defects in two-dimensional (2D) materials can be particularly damaging because they directly impede the transport of charge, spin, or heat and can introduce a metallic character into otherwise semiconducting systems. Current characterization techniques suffer from low throughput and a destructive nature or limitations in their unambiguous sensitivity at the nanoscale. Here we demonstrate that dark-field second harmonic generation (SHG) microscopy can rapidly, efficiently, and nondestructively probe grain boundaries and edges in monolayer dichalcogenides (i.e., MoSe2, MoS2, and WS2). Dark-field SHG efficiently separates the spatial components of the emitted light and exploits interference effects from crystal domains of different orientations to localize grain boundaries and edges as very bright 1D patterns through a Cerenkov-type SHG emission. The frequency dependence of this emission in MoSe2 monolayers is explained in terms of plasmon-enhanced SHG related to the defect's metallic character. This new technique for nanometer-scale imaging of the grain structure, domain orientation and localized 1D plasmons in 2D different semiconductors, thus enables more rapid progress toward both applications and fundamental materials discoveries.

12.
J Neurooncol ; 147(1): 109-116, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31974803

RESUMO

INTRODUCTION: Arterial hypertension and proteinuria are common side effects of antiangiogenic treatment and might represent a biomarker of response in patients with glioblastoma. The aim of this study was to assess the impact of these side effects in predicting therapeutic response to second line chemotherapy with bevacizumab. METHODS: We evaluated clinical and survival data of glioblastoma patients who underwent treatment with bevacizumab after progression under temozolomide, at CHUSJ between 2010 and 2017. We analysed treatment-related arterial hypertension, proteinuria grade, thrombotic and haemorrhagic events during treatment. Overall survival (OS) and progression free survival (PFS) under bevacizumab were calculated according to the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards method. RESULTS: We evaluated 140 patients. Arterial hypertension and proteinuria occurred in 23 (16.3%) and 17 (12.1%) patients, respectively. PFS during treatment with bevacizumab was 12 months (95% CI 7.9-16.1) in the hypertensive group and 4 months (95% CI 3.2-4.8) in the normotensive group (p = 0.005). Patients with proteinuria had a PFS of 10 months (95% CI 4.9-15.0) versus 4 months (95% CI 3.4-4.8) in patients without proteinuria (p = 0.002). Multivariate analysis revealed hypertension and proteinuria as independent prognostic factors of PFS and OS. CONCLUSION: Our data suggest that hypertension and proteinuria can be effective predictors of response to antiangiogenic therapy in recurrent glioblastoma and are associated with longer disease control.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Hipertensão/induzido quimicamente , Proteinúria/induzido quimicamente , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Temozolomida
13.
Ann Vasc Surg ; 66: 470-478, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31863953

RESUMO

BACKGROUND: To evaluate the rates of limb salvage, survival, and perioperative mortality in patients with acute limb ischemia (ALI) submitted to endovascular revascularization with pharmacomechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT). METHODS: This was a retrospective consecutive cohort study of patients with ALI who were submitted to endovascular treatment with PMT or fibrinolysis at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual (São Paulo, Brazil), between July 2015 and December 2018. The limb salvage rate and survival rate at 720 days were analyzed in both the PMT (group 1) and CDT treatment (group 2), as well as the perioperative mortality rate (PMR) at 30 days after surgery. RESULTS: One hundred twelve patients were admitted to the emergency department with ALI between July 2015 and December 2018. Seventeen patients diagnosed with Rutherford III irreversible ALI and 46 patients submitted to open surgery were excluded. Thus, 49 patients were submitted to endovascular surgery; 18 (36.7%) were classified into group 1, and 31 (63.3%) were classified into group 2. The clinical data were equal between the 2 groups, but there was a higher prevalence of thrombophilia in group 1 (3 cases; P < 0.001). The limb salvage rate and the overall survival rate at 720 days were similar between groups 1 and 2 (87.8% vs. 89.7%, P = 0.78 and 84.7% vs. 69.2%, P = 0.82, respectively). There was no statistical difference regarding secondary patency rates at 720 days between groups 1 and 2 (group 1, 81.9% and group 2, 78.8%; P = 0.66). The PMR was 16.7% (8 patients) within the first 30 days. Group 2 had a higher overall mortality rate (OMR) (6 patients, 19.3%, P = 0.03). Regarding the PMT group, there was a higher rate of complications such as myoglobinuria, hematuria, acute renal failure, and death in the subgroup of patients in whom there were performed more than 150 cycles/sec during the surgery (P < 0.001). CONCLUSIONS: In the present study, the PMT and CDT endovascular procedures had similar limb salvage, overall survival, and secondary patency rates. However, the OMR was higher in the CDT group. Another important finding was related to the number of cycles/sec performed in the PMT group, in whom patients with more than 150 cycles/sec have presented with higher rates of hematuria, myoglobinuria, acute renal failure, and death.


Assuntos
Procedimentos Endovasculares , Isquemia/terapia , Doença Arterial Periférica/terapia , Trombectomia , Terapia Trombolítica , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Brasil , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Fatores de Risco , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
14.
Environ Toxicol ; 35(4): 507-517, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31804023

RESUMO

Doxorubicin (Dox) is one of the most successful anticancer drugs in use. However, chemoresistance is one of the main limitations that patients face. Therefore, development of new strategies to improve the efficacy of Dox is needed. Marine-derived fungi are especially promising sources of new anticancer compounds. In this work, antitumor activity of crude ethyl extract of the cultures of the marine-derived fungus Neosartorya siamensis KUFA 0017 (NS), combined with Dox, was evaluated in six cancer cell lines. To evaluate possible mechanisms involved in the eventual improvement of Dox's cytotoxicity by NS extract, effects on DNA damage, cell death, ultrastructural modifications, and intracellular accumulation of Dox were assessed. The NS extract demonstrated a significant enhancement of Dox's cytotoxic activity in A549 cells, inducing DNA damage, cell death, and intracellular accumulation of Dox. Additionally, the cytotoxic effect of eight compounds, isolated from this extract, that is, 2,4-dihydroxy-3-methylacetophenone-(C1), nortryptoquivaline-(C2), chevalone C-(C3), tryptoquivaline H-(C4), fiscalin A-(C5), epi-fiscalin-C (C6), epi-neofiscalin A-(C7), and epi-fiscalin A-(C8), alone and combined with Dox was also evaluated in lung cancer cells. The cytotoxic effect of Dox was potentiated by all the isolated compounds (except C1) in A549 cells. Therefore, we concluded that NS extract potentiated cytotoxicity by inhibiting cell proliferation, increasing intracellular accumulation of Dox, and inducing cell death (possibly by an autophagic process). The isolated compounds also enhanced the activity of Dox, supporting the potential of this sort of combination. These data call for further studies to characterize drug interactions and underlying mechanisms.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Produtos Biológicos/farmacologia , Doxorrubicina/farmacologia , Neosartorya/metabolismo , Células A549 , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Humanos , Indóis/isolamento & purificação , Indóis/metabolismo , Indóis/farmacologia , Neoplasias Pulmonares/patologia , Quinazolinas/isolamento & purificação , Quinazolinas/metabolismo , Quinazolinas/farmacologia
15.
Clin Oral Investig ; 24(9): 3193-3202, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31912243

RESUMO

OBJECTIVE: To verify whether mandibular cortical analyses accurately distinguish postmenopausal women with normal bone mineral density (BMD) from women with osteoporosis by means of a cone-beam computed tomography (CBCT)-driven composite osteoporosis index (three-dimensional mandibular osteoporosis index-3D MOI). MATERIAL AND METHODS: The comparison was performed between 52 women with normal BMD and 51 women with osteoporosis according to dual-energy X-ray absorptiometry (DXA) examination of the lumbar spine and hip. Mandibular cortical width (MCW) and cortical quality were evaluated on cross-sectional and panoramic reconstructed images. ANOVA, ROC curves and accuracy measurements were used for statistical analyses, as well as a predictive model combining the quantitative and qualitative analyses and age. RESULTS: All CBCT-driven measurements presented good to moderate intra- and interobserver agreements. MCW values were significantly lower in women with osteoporosis. Postmenopausal women with osteoporosis were 8 times more likely to have the cortex classified as C3, and 2.4 times more likely to have MCW thinner than 2.75 mm. The area under the ROC curve was 0.8 for the predictive model. CONCLUSIONS: The newly developed 3D MOI enables distinguishing women with osteoporosis from those with normal BMD with good sensitivity and specificity. CLINICAL RELEVANCE: Whenever a CBCT scan is performed for specific clinical indications, a 3D MOI may be performed to qualitatively and quantitatively assess the condition of the mandibular cortex. This may be surely helpful to assess the osteoporosis status in the ageing population and more specifically in peri- or postmenopausal women.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Osteoporose Pós-Menopausa , Osteoporose , Absorciometria de Fóton , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Mandíbula/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Osteoporose Pós-Menopausa/diagnóstico por imagem , Radiografia Panorâmica
16.
Int J Mol Sci ; 21(16)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823572

RESUMO

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults, characterized by a highly aggressive, inflammatory and angiogenic phenotype. It is a remarkably heterogeneous tumor at several levels, including histopathologically, radiographically and genetically. The 2016 update of the WHO Classification of Tumours of the Central Nervous System highlighted molecular parameters as paramount features for the diagnosis, namely IDH1/2 mutations that distinguish primary and secondary GBM. An ideal biomarker is a molecule that can be detected/quantified through simple non- or minimally invasive methods with the potential to assess cancer risk; promote early diagnosis; increase grading accuracy; and monitor disease evolution and treatment response, as well as fundamentally being restricted to one aspect. Blood-based biomarkers are particularly attractive due to their easy access and have been widely used for various cancer types. A number of serum biomarkers with multiple utilities for glioma have been reported that could classify glioma grades more precisely and provide prognostic value among these patients. At present, screening for gliomas has no clinical relevance. This is because of the low incidence, the lack of sensitive biomarkers in plasma, and the observation that gliomas may develop apparently de novo within few weeks or months. To the best of our knowledge, there is no routine use of a serum biomarker for clinical follow-up. The purpose of this paper is to review the serum biomarkers described in the literature related to glioblastoma and their possible relationship with clinical features.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Glioblastoma/sangue , Coagulação Sanguínea , Neoplasias Encefálicas/patologia , DNA Tumoral Circulante/sangue , Glioblastoma/patologia , Humanos , Estado Nutricional
17.
Trop Anim Health Prod ; 52(4): 1661-1668, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31853788

RESUMO

This study aimed to evaluate chromium supplementation on productive, reproductive, and metabolic parameters at lactating Girolando cows subjected to heat stress conditions in a climatic chamber. Thirty-six lactating Girolando cows were subjected to two sequential trials. In trial 1 (thermoneutral environment), the effect of chromium supplementation was evaluated (0 vs. 0.50 mg/kg of dry matter). In trial 2, the cows were fed the same diets, but they were divided into three environmental conditions: heat stress conditions in climatic chamber, fed ad libitum (HS); thermoneutral environment, fed ad libitum (TN); and thermoneutral environment, pair-fed (PF). In thermoneutral conditions, chromium supplementation did not affect productive or metabolic parameters, although supplemented cows had lower viability of oocytes (65.11 ± 0.08% vs. 76.86 ± 0.08%). During heat stress, chromium supplementation lowered plasma glucose levels (61.17 ± 1.90 vs. 67.11 ± 1.90 mg/dL), and increased the insulin:glucose ratio (0.39 ± 0.04 vs. 0.27 ± 0.04). Cows fed the control diet in the HS group had higher vaginal temperature values (39.40 ± 0.10 °C) than the cows in the TN group and PF group (38.89 ± 0.10 °C and 38.85 ± 0.11 °C, respectively). However, supplemented cows heat-stressed maintained the same vaginal temperature as cows in thermoneutral conditions. In conclusion, chromium supplementation improved glucose metabolism and prevented body temperature increases under heat stress conditions.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Cromo/uso terapêutico , Suplementos Nutricionais , Transtornos de Estresse por Calor/prevenção & controle , Resposta ao Choque Térmico , Animais , Bovinos , Cromo/farmacologia , Dieta/veterinária , Feminino , Glucose , Temperatura Alta , Insulina , Lactação , Taxa Respiratória/efeitos dos fármacos , Estresse Fisiológico , Temperatura
18.
J Vasc Surg ; 69(3): 843-849, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30679009

RESUMO

OBJECTIVE: The objective of this study was to evaluate the long-term estimates of limb salvage and survival in patients with acute limb ischemia (ALI) receiving open surgery or endovascular revascularization. METHODS: This was a retrospective consecutive cohort study of patients with ALI who underwent open surgery or endovascular treatment at the Vascular and Endovascular Surgery Unit, Hospital do Servidor Público Estadual (São Paulo, Brazil), between July 2010 and July 2016. The overall mortality, limb salvage, and survival rates at 720 days were analyzed in both the open surgery (group 1) and endovascular treatment (group 2) groups. RESULTS: A total of 69 patients were admitted for a limb salvage procedure. The mean follow-up period was 822 ± 480.5 days. All of the analyses were performed at 720 days. Of the 69 patients, 46 (66.6%) were in group 1 and 23 (33.4%) in group 2. The clinical characteristics were similar between the groups, except for higher rates of chronic kidney disease (P = .04) and arrhythmia (P = .01) in group 1. Group 1 had a higher postoperative ankle-brachial index (P = .03). Concerning the Rutherford classification, group 1 had a higher prevalence of Rutherford IIB ALI (P = .003). The preoperative creatine kinase level was higher in group 1 than in group 2 (780 [range, 198-6546] mg/dL and 245 [65-78] mg/dL, respectively). A creatine kinase level >200 mg/dL was seen in 65.2% and 47.8% of patients in group 1 and group 2, respectively (P = .028). The limb salvage and overall survival estimates at 720 days were similar between group 1 and group 2 (79.2% vs 90.6% [P = .27] and 53% vs 60.8% [P = .45], respectively). The overall mortality rate was 10.1% (seven patients) within the first 30 days, and it was higher in group 1 (six patients [13.0%]; P = .03). CONCLUSIONS: Both open surgery and endovascular procedures are safe treatments of patients with ALI, with acceptable limb salvage and survival rates. No previous study has suggested the preferred treatment of ALI. However, based on this study and the overall literature, endovascular treatment may be the preferred treatment of patients with Rutherford I and IIA ALI; open surgery may be the best option for ALI due to arterial embolism and for Rutherford IIB acute arterial thrombosis because of a greater urgency to restore blood flow.


Assuntos
Procedimentos Endovasculares , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Brasil , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/mortalidade , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade
19.
J Oral Maxillofac Surg ; 77(10): 2126.e1-2126.e8, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31276653

RESUMO

PURPOSE: The purposes were to study the pharyngeal airway in patients with skeletal Class III malocclusion submitted to surgical orthodontic treatment and to correlate the alterations with bone movements. MATERIALS AND METHODS: The sample consisted of multislice computed tomography images from 13 patients obtained before and 6 months after maxillomandibular advancement surgery. The following measurements were obtained using Dolphin Imaging software (Dolphin Imaging, Chatsworth, CA): volume and area of the oropharynx, nasopharynx, and total airway, as well as the most constricted area, anteroposterior and lateral dimensions of the narrowest axial cross-sectional area, and airway length. The paired t test was applied at a significance level of 5%. RESULTS: Sagittal displacement of the maxilla and mandible was correlated with airway alterations using the Pearson correlation test. Alterations in airway measurements were observed in all patients after surgery. We noted a significant increase (P < .05) in total airway area, oropharyngeal area, and anteroposterior dimension of the most constricted area, as well as a significant reduction (P < .05) in airway length. A significant correlation (P < .05) was observed between nasopharyngeal area and maxillary movement and between airway length and mandibular movement (P < .05). CONCLUSIONS: The results of this study suggest significant alterations in pharyngeal airway measurements when preoperative and postoperative periods of bimaxillary advancement surgery were compared.


Assuntos
Má Oclusão Classe III de Angle , Avanço Mandibular , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Tomografia Computadorizada de Feixe Cônico , Humanos , Má Oclusão Classe III de Angle/cirurgia , Mandíbula , Osteotomia Mandibular , Maxila , Faringe
20.
Reprod Domest Anim ; 54(10): 1357-1365, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31368591

RESUMO

This study investigated the influence of heat shock during in vitro maturation on embryo development following in vitro fertilization (IVF) or parthenogenesis (Part). Immature bovine cumulus-oocyte complexes were exposed to heat shock (41.0°C) during the first 12 hr of in vitro maturation (IVM), followed by 12 hr at 38.5°C. Control group consisted of in vitro maturation for 24 hr at 38.5°C. Oocytes were in vitro-fertilized or activated with ionomycin and cultured in vitro for 192 hr post-in vitro insemination or parthenogenetic activation (hpia). There was an interaction (p < .01) between temperature of IVM and method of oocyte activation (IVF or Part) for cleavage at 48 hpia. Heat shock had a negative impact (p < .01) on cleavage of IVF embryos, whereas no (p > .05) effect was found in the Part embryos. Embryo development towards blastocyst stage at 168 and 192 hpia decreased in both IVF and Part embryos derived from heat-shocked oocytes. Heat shock increased (p < .05) the apoptotic index in Part blastocysts, but no effect (p > .05) was found in IVF counterparts. Heat shock also down-regulated the expression of AQP3 (p < .01) and up-regulated the expression of HSP70.1 (p < .01) in Part blastocysts, whereas it down-regulated the expression of ATP1A1 (p < .05) in IVF blastocysts. In conclusion, the effects of heat shock during IVM on early embryo cleavage and blastocyst apoptosis are influenced by the method of oocyte activation and expression of some genes can be disturbed in embryos derived from heat-shocked oocytes.


Assuntos
Blastocisto/fisiologia , Bovinos/embriologia , Resposta ao Choque Térmico/fisiologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Partenogênese/fisiologia , Animais , Células do Cúmulo , Desenvolvimento Embrionário , Feminino , Fertilização in vitro/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Masculino , Oócitos
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