Browsing by Issue Date, starting with "2020-10"
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- Mesenchymal stromal cells’ therapy for polyglutamine disorders: where do we stand and where should we go?Publication . Barros, Inês; Marcelo, Adriana; Silva, Teresa P.; Barata, João; Rufino-Ramos, David; Pereira de Almeida, Luís; Miranda, Catarina O.Polyglutamine (polyQ) diseases are a group of inherited neurodegenerative disorders caused by the expansion of the cytosine-adenine-guanine (CAG) repeat. This mutation encodes extended glutamine (Q) tract in the disease protein, resulting in the alteration of its conformation/physiological role and in the formation of toxic fragments/aggregates of the protein. This group of heterogeneous disorders shares common molecular mechanisms, which opens the possibility to develop a pan therapeutic approach. Vast efforts have been made to develop strategies to alleviate disease symptoms. Nonetheless, there is still no therapy that can cure or effectively delay disease progression of any of these disorders. Mesenchymal stromal cells (MSC) are promising tools for the treatment of polyQ disorders, promoting protection, tissue regeneration, and/or modulation of the immune system in animal models. Accordingly, data collected from clinical trials have so far demonstrated that transplantation of MSC is safe and delays the progression of some polyQ disorders for some time. However, to achieve sustained phenotypic amelioration in clinics, several treatments may be necessary. Therefore, efforts to develop new strategies to improve MSC's therapeutic outcomes have been emerging. In this review article, we discuss the current treatments and strategies used to reduce polyQ symptoms and major pre-clinical and clinical achievements obtained with MSC transplantation as well as remaining flaws that need to be overcome. The requirement to cross the blood-brain-barrier (BBB), together with a short rate of cell engraftment in the lesioned area and low survival of MSC in a pathophysiological context upon transplantation may contribute to the transient therapeutic effects. We also review methods like pre-conditioning or genetic engineering of MSC that can be used to increase MSC survival in vivo, cellular-free approaches-i.e., MSC-conditioned medium (CM) or MSC-derived extracellular vesicles (EVs) as a way of possibly replacing the use of MSC and methods required to standardize the potential of MSC/MSC-derived products. These are fundamental questions that need to be addressed to obtain maximum MSC performance in polyQ diseases and therefore increase clinical benefits.
- Brachyury Is associated with glioma differentiation and response to temozolomidePublication . Pinto, Filipe; Costa, Angela M.; Andrade, Raquel P.; Reis, Rui ManuelGlioblastomas (GBMs) are the most aggressive tumor type of the central nervous system, mainly due to their high invasiveness and innate resistance to radiotherapy and chemotherapy, with temozolomide (TMZ) being the current standard therapy. Recently, brachyury was described as a novel tumor suppressor gene in gliomas, and its loss was associated with increased gliomagenesis. Here, we aimed to explore the role of brachyury as a suppressor of glioma invasion, stem cell features, and resistance to TMZ. Using gene-edited glioma cells to overexpress brachyury, we found that brachyury-positive cells exhibit reduced invasive and migratory capabilities and stem cell features. Importantly, these brachyury-expressing cells have increased expression of differentiation markers, which corroborates the results from human glioma samples andin vivotumors. Glioma cells treated with retinoic acid increased the differentiation status with concomitant increased expression of brachyury. We then selected TMZ-resistant (SNB-19) and TMZ-responsive (A172 and U373) cell lines to evaluate the role of brachyury in the response to TMZ treatment. We observed that both exogenous and endogenous brachyury activation, through overexpression and retinoic acid treatment, are associated with TMZ sensitization in glioma-resistant cell lines. In this study, we demonstrate that brachyury expression can impair aggressive glioma features associated with treatment resistance. Finally, we provide the first evidence that brachyury can be a potential therapeutic target in GBM patients who do not respond to conventional chemotherapeutic drugs.
- Chemical profile, antioxidant, antimicrobial, enzyme inhibitory, and cytotoxicity of seven Apiaceae species from Turkey: a comparative studyPublication . Zengin, Gokhan; Sinan, Kouadio Ibrahime; Ak, Gunes; Mahomoodally, Mohamad Fawzi; Paksoy, Mehmet Yavuz; Picot-Allain, Carene; Glamocilja, Jasmina; Sokovic, Marina; Jeko, Jozsef; Cziaky, Zoltan; Rodrigues, Maria Joao; Pereira, Catarina; Custódio, LuísaSeveral Apiaceae species, used as both food and in complementary and alternative medicine, represents a rich source of potential valuable phytopharmaceuticals which necessitates scientific contemplation. In the present study, the antioxidant, enzyme inhibitory, antimicrobial, and cytotoxic properties of methanol extracts of seven Apiaceae species, (Chaerophyllum macrospermum (Willd. ex Spreng.) Fisch. & C.A.Mey. ex Hohen, Ferula rigidula Fisch. ex DC., Ferula orientalis L., Prangos ferulacea Lindl., Prangos peucedanifolia Fenzl., Ferulago setifolia K. Koch, and Pimpinella anthriscoides Boiss.) were evaluated. Species belonging to the Prangos genus exhibited the highest total phenolic content, namely P. peucedanifolia and P. ferulacea, with values of 47.90 and 44.44 mg gallic acid equivalent/g extract, respectively. P. peucedanifolia also displayed the highest radical scavenging capacity (81.53 and 102.70 mg Trolox equivalent [TE]/g extract for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), respectively) and reducing power (165.87 and 100.09 mg TE/g extract for cupric reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP), respectively). C. macrospermum showed the most potent inhibition against Alzheimer's disease related enzymes, namely acetylcholinesterase (4.53 mg galantamine equivalent [GALAE]/g extract) and butyrylcholinesterase (3.22 mg GALAE/g extract). P. ferulacea (131.94 mg kojic acid (KAE) equivalent/g extract) and P. peucedanifolia (4.97 mmol acarbose equivalent (ACAE)/g extract) were potent inhibitors of tyrosinase and a-glucosidase, respectively. In general, studied species were able to reduce cellular viabilities. P. peucedanifolia possessed promising antibacterial potential against Bacillus cereus (Minimum inhibition concentration (MIC): 0.37 mg/mL), L. monocytogenes (MIC: 0.56 mg/mL), P. aeruginosa and Escherichia coli (MIC: 0.27 mg/mL), Salmonella typhimurium and Enterobacter cloacae (MIC: 0.75 mg/mL). F. rigidula showed the highest antifungal effect against Aspergillus ochraceus and Trichoderma viride (MIC: 0.10 mg/mL). The present findings could be the scientific starting point towards the pharmaceutical and/or commercial utilization of these Apiaceae species.
- Bond-breaking/Bond-forming reactions by vibrational excitation: infrared-induced bidirectional tautomerization of matrix-isolated thiotropolonePublication . Nunes, Claudio M.; Pereira, Nelson A. M.; Reva, Igor; Amado, Patrícia; Cristiano, Maria De Lurdes; Fausto, RuiInfrared vibrational excitation is a promising approach for gaining exceptional control of chemical reactions, in ways that cannot be attained via thermal or electronic excitation. Here, we report an unprecedented example of a bond-breaking/bond-forming reaction by vibrational excitation under matrix isolation conditions. Thiotropolone monomers were isolated in cryogenic argon matrices and characterized by infrared spectroscopy and vibrational computations (harmonic and anharmonic). Narrowband near-infrared irradiations tuned at frequencies of first CH stretching overtone (5940 cm(-1)) or combination modes (5980 cm(-1)) of the OH tautomer, the sole form of the compound that exists in the as-deposited matrices, led to its conversion into the SH tautomer. The tautomerization in the reverse direction was achieved by vibrational excitation of the SH tautomer with irradiation at 5947 or 5994 cm(-1), corresponding to the frequencies of its CH stretching combination and overtone modes. This pioneer demonstration of bidirectional hydroxyl. thiol tautomerization controlled by vibrational excitation creates prospects for new advances in vibrationally induced chemistry.
- The effect of UV-C and electrolyzed water on yeasts on fresh-cut apple at 4 degrees CPublication . Graça, Ana; Santo, David; Pires-Cabral, Paula; Quintas, CéliaThe growth of a yeast mixture, Candida sake, Hanseniaspora uvarum, Pichia fermentans, Metschnikowia pulcherrima, on fresh-cut apple (Royal gala), at 4 degrees C, was studied, as well as the reduction of yeasts using Ultraviolet-C (UV-C), acidic (AEW) and neutral (NEW) electrolyzed waters, and sodium hypochlorite (SH). Apple portions were contaminated then disinfected with UV-C (2.5-10 kJ/m(2)), AEW, NEW and SH (100 ppm). During 9 days at 4 degrees C, yeasts growth rate was 0.34 day(-1) and the stationary phase occurred after 6 days (7.42 LogCFU/g). The initial microbial reduction and the half-life time values, using the inverse hyperbola model, ranged from 1.72 to 1.81 LogCFU/g and 6.52-11.70 day (UV-C), or 0.91 to 1.96 LogCFU/g and 0.68-4.38 day (chemical treatments), where SH was the least efficient (0.92 LogCFU/g and 2.96 day). The most effective treatment was UV-C (7.5 and 10 kJ/m(2)). The yeasts psychrotrophic profile highlights the importance of avoiding contamination/cross-contaminations in all processing.
- Skeletal muscle expression of adipose-specific phospholipase in peripheral artery diseasePublication . Parmer, Caitlin; De Sousa-Coelho, Ana Luísa; Cheng, Henry S.; Daher, Grace; Burkart, Alison; Dreyfuss, Jonathan M.; Pan, Hui; Prenner, Joshua C.; Keilson, Jessica M.; Pande, Reena; Henkin, Stanislav; Feinberg, Mark W.; Patti, Mary Elizabeth; Creager, Mark A.Flow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) wasPLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR;PLA2G16was downregulated by 68% in patients with PAD (p< 0.001). Expression ofPla2g16was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression ofPla2g16in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.
- Hadamard-Bergman Convolution OperatorsPublication . Karapetyants, Alexey; Samko, StefanWe introduce a convolution form, in terms of integration over the unit disc D, for operators on functions f in H(D), which correspond to Taylor expansion multipliers. We demonstrate advantages of the introduced integral representation in the study of mapping properties of such operators. In particular, we prove the Young theorem for Bergman spaces in terms of integrability of the kernel of the convolution. This enables us to refer to the introduced convolutions as Hadamard-Bergman convolution. Another, more important, advantage is the study of mapping properties of a class of such operators in Holder type spaces of holomorphic functions, which in fact is hardly possible when the operator is defined just in terms of multipliers. Moreover, we show that for a class of fractional integral operators such a mapping between Holder spaces is onto. We pay a special attention to explicit integral representation of fractional integration and differentiation.
- New palynostratigraphic data of the Irati (Assistencia Member) and the Corumbatai formations, Parana Basin, Brazil, and correlation with other south American basinsPublication . Rocha, H., V; Mendes, M.; Pereira, Z.; Rodrigues, C.; Manuel Carvalho Fernandes, Paulo; Lopes, Gilda; Sant'Anna, L. G.; Tassinari, C. C. G.; Lemos de Sousa, M. J.This research presents the palynostratigraphy of organic-rich shales from the Irati and the Corumbatai formations, Parana Basin (PB), Southeastern Brazil, as part of an unconventional hydrocarbon source rock and CO2 reservoir assessment study. Thirty-four samples from the Corumbatai Formation and the Assistencia Member of the Irati Formation were collected in the states of Goias (northern border of the PB), Sao Paulo and Parana (eastern and southern border of the PB, respectively). The acquired data allowed to establish a comprehensive palynostratigraphic study across the basin where a total of 18 pollen genera (34 pollen species), seven spore genera, four microplankton genera (1 species), and Chlorophyceae algae species where identified. The palynostratigraphic analysis also reveals a clear dominance of bisaccate pollen grains such as Corisaccites alutas, Lueckisporites virkkiae, and Weylandites lucifer. The Lueckisporites virkkiae zone was identified in the upper part of the Irati Formation (Assistencia Member) and the lowermost part of the Corumbatai Formation, indicating a Kungurian to Roadian age for this part of the succession. Differences in the Guttulapollenites hannonicus and Tornopollenites toreutos biostratigraphic ranges, recovered in the Corumbatai Formation, suggest an earlier development of these species in the Parana Basin during the middle Permian. Therefore, to evaluate the differences in the first occurrences of key species within the Parana Basin, a close palynostratigraphic correlation between the main Guadalupian-Lopingian South American Gondwana basins is tentatively established.
- Facets of congruence distributivity in Goursat categoriesPublication . Gran, Marino; Rodelo, Diana; Nguefeu, Idriss TchoffoWe give new characterisations of regular Mal'tsev categories with distributive lattice of equivalence relations through variations of the so-called Triangular Lemma and Trapezoid Lemma in universal algebra. We then give new characterisations of equivalence distributive Goursat categories (which extend 3-permutable varieties) through variations of the Triangular and Trapezoid Lemmas involving reflexive and positive relations. (C) 2020 Elsevier B.V. All rights reserved.
- Role of individual and organizational variables as predictors of job satisfaction among hotel employeesPublication . Viseu, J.; Patrícia Valle, Patrícia Oom do Valle; Borralha, Sergio; Jesus, SaúlJob satisfaction is a key concept in the organizational literature, as satisfied employees allow organizations to achieve desired work-related outcomes. Nevertheless, more research is needed to understand what organizational and individual variables shape the job satisfaction of employees from the hospitality sector. This study assesses the role of organizational variables (perceived organizational support and organizational health) and individual variables (positive psychological capital and creative personality) as possible determinants of job satisfaction. A total of 504 hotel employees from the Algarve region, the main Portuguese tourism destination, participated in this study. Structural equation modeling with latent variables was used to evaluate the proposed model. Results showed that perceived organizational support was the most important predictor of job satisfaction, followed by organizational health. Organizational health also predicted positive psychological capital, which, in turn, was significantly associated with job satisfaction. These results have important practical implications for human resources management in the hospitality industry.