A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer

Metabolic remodeling is a critical skill of malignant cells, allowing their survival and spread. The metabolic dynamics and adaptation capacity of cancer cells allow them to escape from damaging stimuli, including breakage or cross-links in DNA strands and increased reactive oxygen species (ROS) levels, promoting resistance to currently available therapies, such as alkylating or oxidative agents. Therefore, it is essential to understand how metabolic pathways and the corresponding enzymatic systems can impact on tumor behavior. Cysteine aminotransferase (CAT) per se, as well as a component of the CAT: 3-mercaptopyruvate sulfurtransferase (MST) axis, is pivotal for this metabolic rewiring, constituting a central mechanism in amino acid metabolism and fulfilling the metabolic needs of cancer cells, thereby supplying other different pathways. In this review, we explore the current state-of-art on CAT function and its role on cancer cell metabolic rewiring as MST partner, and its relevance in cancer cells' fitness.publishersversionpublishe

Design and Implementation of a New Layout in a New Production Area of a Cork Stopper Factory Following Lean Manufacturing Principles

Publisher Copyright: © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.The current market conditions and purchasing power put pressure on selling prices. To maintain corporate profits, it is important to increase manufacturing efficiency and lower costs. The industrial unit in which this project was developed aims to increase the annual production of cork stoppers and by doing so, maintain the high standards of the quality and accuracy in their processes. To respond to this growth, Lean Manufacturing was implemented, and it was decided to build a new production area. The goal is to create a new production area for cork stoppers capable of producing around half a million cork stoppers per day. The use of Total Flow Management (TFM) tools allowed for the design of the layout and to level production. With the construction of a continuous flow between processes, the storage areas were gradually reduced, and the volume of WIP stock decreased by 63%. The results have also shown a decrease in the complaint rate of 3.5%, which was reduced under the established threshold of 5%, fulfilling the objectives proposed by the company for the project.publishe

Causas de incêndios florestais em Portugal continental. Análise estatística da investigação efetuada no último quindénio (1996 a 2010)

Ao longo dos últimos anos, Portugal não tem conseguido travar os incêndios florestais, tanto no que diz respeito número de ocorrências como no que se refere à dimensão das áreas ardidas, sobretudo durante o período estival, quando dominam temperaturas elevadas e a dessecação dos combustíveis gera um ambiente propício à propagação dos incêndios, cuja ignição, em mais de 90% dos casos, tem origem em atos humanos, negligentes e intencionais. Com o objetivo de melhor compreender a origem destes incêndios florestais, o presente estudo visa analisar as causas responsáveis pela ignição dos incêndios florestais em Portugal e acompanhar o modo como elas foram evoluindo, quer ao longo do tempo, quer em termos da sua distribuição espacial, no período compreendido entre 1996 e 2010

Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming

Funding Information: Funding. This research was supported by Funda??o para a Ci?ncia e Tecnologia (FCT) (Ph.D. ProRegeM program, Ref: PD/BD/105893/2014; FCT individual Ph.D. fellowship Ref: 2020.06956.BD) and iNOVA4 Health (Project 4 and Project 21). iNOVA4Health-UID/Multi/04462/2013 is a program financially supported by Funda??o para a Ci?ncia e Tecnologia/ Minist?rio da Educa??o e Ci?ncia, through national funds. The authors would like to acknowledge the Instituto Portugu?s de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. Publisher Copyright: © Copyright © 2021 Nunes, Ramos, Santos, Mendes, Silva, Vicente, Pereira, Félix, Gonçalves and Serpa.Among gynecologic malignancies, ovarian cancer is the third most prevalent and the most common cause of death, especially due to diagnosis at an advanced stage together with resistance to therapy. As a solid tumor grows, cancer cells in the microenvironment are exposed to regions of hypoxia, a selective pressure prompting tumor progression and chemoresistance. We have previously shown that cysteine contributes to the adaptation to this hypoxic microenvironment, but the mechanisms by which cysteine protects ovarian cancer cells from hypoxia-induced death are still to be unveiled. Herein, we hypothesized that cysteine contribution relies on cellular metabolism reprogramming and energy production, being cysteine itself a metabolic source. Our results strongly supported a role of xCT symporter in energy production that requires cysteine metabolism instead of hydrogen sulfide (H2S) per se. Cysteine degradation depends on the action of the H2S-synthesizing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (MpST; together with cysteine aminotransferase, CAT). In normoxia, CBS and CSE inhibition had a mild impact on cysteine-sustained ATP production, pointing out the relevance of CAT + MpST pathway. However, in hypoxia, the concomitant inhibition of CBS and CSE had a stronger impact on ATP synthesis, thus also supporting a role of their hydrogen sulfide and/or cysteine persulfide-synthesizing activity in this stressful condition. However, the relative contributions of each of these enzymes (CBS/CSE/MpST) on cysteine-derived ATP synthesis under hypoxia remains unclear, due to the lack of specific inhibitors. Strikingly, NMR analysis strongly supported a role of cysteine in the whole cellular metabolism rewiring under hypoxia. Additionally, the use of cysteine to supply biosynthesis and bioenergetics was reinforced, bringing cysteine to the plateau of a main carbon sources in cancer. Collectively, this work supports that sulfur and carbon metabolism reprogramming underlies the adaptation to hypoxic microenvironment promoted by cysteine in ovarian cancer.publishersversionpublishe

Isolated traumatic dislocation of the cuboid

The cuboid bone stabilizes the lateral column of the foot. It articulates with the midtarsal and tarsometatarsal joints and this anatomically proportionates marked stability to the cuboid. Isolated dislocations of the cuboid a rare ocurrence. The authors present a rare case of an isolated traumatic dislocation of the cuboid bone without fracture and present a short review of the pertinent literature

Electrochemical CO2 reduction at room temperature and mild pressures

ABSTRACT: Carbon capture and utilization technologies (CCU) and electrolytic hydrogen production are closely interconnected technologies and necessary for a sustainable energy system. This work describes the development of a process for room temperature co-electrolysis of CO2 and water to produce syngas, at mild pressures. The influence of several parameters in the performance of the process is reported.N/

Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity

The authors would like to acknowledge the Instituto Portugues de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. We would also like to acknowledge Dr Dialina Brilhante and Dr. Teresa Guerreiro (Servico de Imuno-hemoterapia, IPOLFG) for providing blood donors samples; to Dr Humberto Goncalves (Pharmacy, IPOLFG) for paclitaxel and carboplatin preparation, and Marta Teixeira (IBET) for the technical support in 3D models. The study was also funded by Projecto TVI. This research was supported by Fundacao para a Ciencia e Tecnologia (FCT) (PhD ProRegeM program, PD/BD/105893/2014, FCT fellowship, PD/BD/105768/2014). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged.Ovarian cancer is the second most common gynaecologic malignancy and the main cause of death from gynaecologic cancer, due to late diagnosis and chemoresistance. Studies have reported the role of cysteine in cancer, by contributing for hydrogen sulphide (H2S) generation and as a precursor of glutathione (GSH). However, the role of cysteine in the adaptation to hypoxia and therapy response remains unclear. We used several ovarian cancer cell lines, ES2, OVCAR3, OVCAR8, A2780 and A2780cisR, to clarify cysteine relevance in ovarian cancer cells survival upon hypoxia and carboplatin. Results show that ES2 and OVCAR8 cells presented a stronger dependence on cysteine availability upon hypoxia and carboplatin exposure than OVCAR3 cells. Interestingly, the A2780 cisR, but not A2780 parental cells, benefits from cysteine upon carboplatin exposure, showing that cysteine is crucial for chemoresistance. Moreover, GSH degradation and subsequent cysteine recycling pathway is associated with ovarian cancer as seen in peripheral blood serum from patients. Higher levels of total free cysteine (Cys) and homocysteine (HCys) were found in ovarian cancer patients in comparison with benign tumours and lower levels of GSH were found in ovarian neoplasms patients in comparison with healthy individuals. Importantly, the total and S-Homocysteinylated levels distinguished blood donors from patients with neoplasms as well as patients with benign from patients with malignant tumours. The levels of S-cysteinylated proteins distinguish blood donors from patients with neoplasms and the free levels of Cys in serum distinguish blood from patients with benign tumours from patients with malignant tumours. Herein we disclosed that cysteine contributes for a worse disease prognosis, allowing faster adaptation to hypoxia and protecting cells from carboplatin. The measurement of serum cysteine levels can be an effective tool for early diagnosis, for outcome prediction and follow up of disease progression.publishersversionpublishe

Electrochemical production of syngas from CO2 at pressures up to 30 bar in electrolytes containing ionic liquid

ABSTRACT: Electrochemical CO2 reduction in a reactor that can operate up to 100 bar and 80 degrees C, with a configuration similar to that of an alkaline electrolyser, for hydrogen production suitable to be used industrially is reported for the first time. The effect of pressure on the co-electrolysis of CO2 and water was studied. The successful scale-up from a previously reported batch process to electrodes of ca. 30 cm(2) geometrical area (30-fold factor) that combines the use of pressure and an ionic liquid-based electrolyte is presented. Also for the first time, the potential of the system under study to achieve high conversions of CO2 to avoid a purification step of syngas from unreacted CO2 is shown. An inexpensive commercial foil of the common metal zinc was employed. A semi-continuous operation yielded syngas productivities in the range of 0.02-0.04 mmol cm(-2) h(-1) at ca. -1.2 V vs. QRE Ag/Ag+. When an electrolyte consisting of 90 wt% H2O and 10 wt% 1-ethyl-3-methylimidazolium trifluoromethanesulfonate was used, selectivities for CO in the range of 62% to 72% were obtained at 10 bar pressure, whereas selectivities of 82% were obtained at 30 bar pressure. H-2/CO ratios in the range of 1/1 to 4/1 at 10 bar pressure suitable for the synthesis of a variety of fuels, such as hydrocarbons, methanol, methane and chemical building blocks, were observed. An energy efficiency of 44.6% was calculated for a H-2/CO ratio of 2.2 suitable for the synthesis of methanol.info:eu-repo/semantics/publishedVersio