Visfatin, glucose metabolism and vascular disease: a review of evidence

The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease

AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT) and the Assistance Program and Incentive Research (PAIP), Barretos Cancer Hospital São Paulo, Brazil. The authors would like to acknowledge the technical support of Gabriela Lamberti in the clonogenic assays. A.L.C and R.M.R are recipients of a National Counsel of Technological and Scientific Development (CNPq) scholarship and O.C.M is recipient of a Portuguese Foundation for Science and Technology (FCT) scholarship (SFRH/BPD/108351/2015)info:eu-repo/semantics/publishedVersio

Process simulation and techno-economic assessment for direct production of advanced bioethanol using a genetically modified Synechocystis sp.

ABSTRACT: A techno-economic assessment for the direct production of ethanol using a genetically-modified microalgae has been studied. It was considered two main scenarios for process modelling: i) bioenergy-driven microalgae plant, i.e., focused on the production of fuel-grade ethanol and biogas for CHP and, ii) biorefinery-driven microalgae plant, focused on the recovery of added-value bioproducts (zeaxanthin and phycocyanin) along with ethanol and CHP production. These main scenarios and several variants were modelled and optimized for a small-scale demo plant of 1000 Lethanol/day and extrapolated for larger production capacities. Results showed that despite the innovative approach of direct production of ethanol by microalgae, the bioenergy-driven scenario is non-feasible under the studied conditions. Conversely, ethanol production becomes economically feasible as co-product in the biorefinery-driven scenario although having payback periods>10 years. Furthermore, if only bio-based products are produced the NPV and the payback are even more positive, 104.8 M€ and ca. 5 years, respectively.info:eu-repo/semantics/publishedVersio

C+L band gain equalization for extended reach WDM-ring PON using hybrid Raman/in line EDFA amplification

“Copyright © [2010] IEEE. Reprinted from ICTON 2010. ISBN 978-1-4244-7798-2. This material is posted here with permission of the IEEE. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.”In this paper, we investigate by simulation the feasibility of gain enlargement and equalization on extended reach WDM-ring PON by means of hybrid Raman/EDFA amplification. The system under analysis is composed by a bidirectional pump at 1480 nm and 16 channels (8 C band + 8 L band). The simulation describes an 80 km WDM ring with 8 nodes in which 2 channels are added/dropped. The results demonstrate gain equalization with a ripple of 2.54 dB over a bandwidth of 50 nm by using a 1480 nm bidirectional pump with 1 W and spans of EDF with a total length of 22 m

Falha de resposta à glibenclamida em criança brasileira com diabetes melito neonatal permanente e síndrome DEND devido a mutação C166Y no gene KCNJ11 (Kir6.2)

Heterozygous activating mutations of KCNJ11 (Kir6.2) are the most common cause of permanent neonatal diabetes mellitus (PNDM) and several cases have been successfully treated with oral sulfonylureas. We report on the attempted transfer of insulin therapy to glibenclamide in a 4-year old child with PNDM and DEND syndrome, bearing a C166Y mutation in KCNJ11. An inpatient transition from subcutaneous NPH insulin (0.2 units/kg/d) to oral glibenclamide (1 mg/kg/d and 1.5 mg/kg/d) was performed. Glucose and C-peptide responses stimulated by oral glucose tolerance test (OGTT), hemoglobin A1c levels, the 8-point self-measured blood glucose (SMBG) profile and the frequency of hypoglycemia episodes were analyzed, before and during treatment with glibenclamide. Neither diabetes control nor neurological improvements were observed. We concluded that C166Y mutation was associated with a form of PNDM insensitive to glibenclamide.As mutações ativadoras, heterozigóticas do gene KCNJ11 (Kir6.2) são a causa mais freqüente de diabetes melito neonatal permanente (DMNP) e a terapêutica oral com sulfoniluréias tem sido bem sucedida em muitos destes casos. Relatamos o processo de substituição da insulinoterapia convencional para o tratamento oral com glibenclamida em uma paciente de 4 anos, portadora de DMNP e síndrome DEND devido a uma mutação C166Y no gene KCNJ11. A insulina NPH (0,2 U/kg/dia) foi substituída pela glibenclamida (1 mg/kg/dia e 1,5 mg/kg/dia) durante internação hospitalar. As respostas de glicose e peptídeo-C no teste de tolerância oral à glicose (OGTT), os níveis de hemoglobina glicada, o perfil de glicemias capilares de 8 pontos e a freqüência de hipoglicemias foram comparados antes e durante o tratamento com glibenclamida. Não houve melhora no controle glicêmico, nem no quadro neurológico. Concluímos que a mutação C166Y associa-se a uma forma de DMNP insensível à glibenclamida

Caracterização da produção agroecológica do sul do Rio Grande do Sul e sua relação com a mecanização agrícola.

A agricultura agroecológica tem-se destacado como uma das alternativas de renda para os pequenos agricultores devido à crescente busca por parte da população por alimentação mais saudável. No Rio Grande do Sul, a Associação Regional de Produtores Agroecológicos da Região Sul (Arpasul), constituída por 48 famílias, é representativa do processo de produção e de comercialização de produtos agroecológicos, servindo como referencial para o presente estudo. O objetivo principal deste trabalho foi o levantamento das necessidades dos produtores agroecológicos em relação à mecanização agrícola. As informações obtidas foram baseadas no sistema de produção utilizado, sendo caracterizados aspectos referentes à propriedade, às operações agrícolas e às necessidades específicas de máquinas e implementos. Por meio deste estudo, foi evidenciada a carência no atendimento das demandas específicas, na área de máquinas agrícolas para esse segmento, podendo servir como referencial para o desenvolvimento de novas máquinas e/ou aperfeiçoamento das existentes. A semeadora de milho e feijão foi a máquina que a maioria dos agricultores pesquisados indicou como sua maior necessidade

Comprehensive molecular landscape of cetuximab resistance in head and neck cancer cell lines

Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model. We established a cetuximab resistant model (FaDu), using increased cetuximab concentrations for more than eight months. The resistance and parental cells were evaluated for cell viability and functional assays. Protein expression was analyzed by Western blot and human cell surface panel by lyoplate. The mutational profile and copy number alterations (CNA) were analyzed using whole-exome sequencing (WES) and the NanoString platform. FaDu resistant clones exhibited at least two-fold higher IC50 compared to the parental cell line. WES showed relevant mutations in several cancer-related genes, and the comparative mRNA expression analysis showed 36 differentially expressed genes associated with EGFR tyrosine kinase inhibitors resistance, RAS, MAPK, and mTOR signaling. Importantly, we observed that overexpression of KRAS, RhoA, and CD44 was associated with cetuximab resistance. Protein analysis revealed EGFR phosphorylation inhibition and mTOR increase in resistant cells. Moreover, the resistant cell line demonstrated an aggressive phenotype with a significant increase in adhesion, the number of colonies, and migration rates. Overall, we identified several molecular alterations in the cetuximab resistant cell line that may constitute novel biomarkers of cetuximab response such as mTOR and RhoA overexpression. These findings indicate new strategies to overcome anti-EGFR resistance in HNSCC.This work was supported by Barretos Cancer Hospital and the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer) in Campinas, Brazil, CAPESDFATD (88887.137283/2017-00). INFG is the recipient of a FAPESP Ph.D. fellowship (2017/22305-9)

Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer.The authors acknowledge the Avon Institute for sponsoring this study. The authors would like to thank the Barretos Cancer Hospital's Research Support Nucleus for patient identification, sample selection, and biostatistics support, as well as Barretos Cancer Hospital's Tumor Bank for sample provision and RNA extraction.info:eu-repo/semantics/publishedVersio