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Article ; Online: Alternative Dosing Schedules of Azacitidine: A Real-World Study Across South American Centers.

Castelo, Lucas / da Silva, Wellington Fernandes / Lincango, Marco / Buccheri, Valeria / Perusini, Agustina / Arbelbide, Jorge / Iastrebner, Marcelo / Gonzalez, Jacqueline / Pereyra, Patricio / Pereira, Thales Dalessandro M / Marchi, Luan Lima / Rocha, Vanderson / Belli, Carolina B / Velloso, Elvira Deolinda Rodrigues Pereira

Clinical lymphoma, myeloma & leukemia

2024

Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Letter
ZDB-ID	2540992-X
ISSN	2152-2669 ; 2152-2650
ISSN (online)	2152-2669
ISSN	2152-2650
DOI	10.1016/j.clml.2024.02.003
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Zs.A 5903: Show issues

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Article: Impressive and durable clinical responses obtained with dabrafenib and trametinib in low-grade serous ovarian cancer harbouring a BRAF V600E mutation.

Lima, Bárbara / Abreu, Miguel Henriques / Sousa, Susana / Bartosch, Carla / Pereira, Deolinda

Gynecologic oncology reports

2022 Volume 40, Page(s) 100942

Abstract: Low-grade serous ovarian cancer (LGSOC) is now considered a different entity from high-grade serous ovarian cancer. The chemoresistance inherent to this type of ovarian cancer narrows the therapeutic options, especially in the recurrent setting. It is ... ...

Abstract	Low-grade serous ovarian cancer (LGSOC) is now considered a different entity from high-grade serous ovarian cancer. The chemoresistance inherent to this type of ovarian cancer narrows the therapeutic options, especially in the recurrent setting. It is thought that the mitogen-activated protein kinase (MAPK) pathway plays a significant role in the pathogenesis of these tumours, and about 2 to 20% of LGSOC harbour a BRAF mutation. Here we present a case report of two patients with a BRAF V600E mutation that achieved sustained clinical responses with combination treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor).
Language	English
Publishing date	2022-02-23
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	2818505-5
ISSN	2352-5789
ISSN	2352-5789
DOI	10.1016/j.gore.2022.100942
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Article ; Online: Secretome of bone marrow mesenchymal stromal cells cultured in a dynamic system induces neuroprotection and modulates microglial responsiveness in an α-synuclein overexpression rat model.

Marques, Cláudia Raquel / Campos, Jonas / Sampaio-Marques, Belém / Antunes, Filipa Ferreira / Dos Santos Cunha, Raquel Medina / Silva, Deolinda / Barata-Antunes, Sandra / Lima, Rui / Fernandes-Platzgummer, Ana / da Silva, Cláudia L / Sousa, Rui Amandi / Salgado, António José

Cytotherapy

2024

Abstract: Background aims: Parkinson's disease (PD) is the second most common neurodegenerative disorder. The etiology of the disease remains largely unknown, but evidence have suggested that the overexpression and aggregation of alpha-synuclein (α-syn) play key ... ...

Abstract	Background aims: Parkinson's disease (PD) is the second most common neurodegenerative disorder. The etiology of the disease remains largely unknown, but evidence have suggested that the overexpression and aggregation of alpha-synuclein (α-syn) play key roles in the pathogenesis and progression of PD. Mesenchymal stromal cells (MSCs) have been earning attention in this field, mainly due to their paracrine capacity. The bioactive molecules secreted by MSCs, i.e. their secretome, have been associated with enhanced neuronal survival as well as a strong modulatory capacity of the microenvironments where the disease develops. The selection of the appropriate animal model is crucial in studies of efficacy assessment. Given the involvement of α-syn in the pathogenesis of PD, the evidence generated from the use of animal models that develop a pathologic phenotype due to the action of this protein is extremely valuable. Therefore, in this work, we established an animal model based on the viral vector-mediated overexpression of A53T α-syn and studied the impact of the secretome of bone marrow mesenchymal stromal cells MSC(M) as a therapeutic strategy. Methods: Adult male rats were subjected to α-syn over expression in the nigrostriatal pathway to model dopaminergic neurodegeneration. The impact of locally administered secretome treatment from MSC(M) was studied. Motor impairments were assessed throughout the study coupled with whole-region (striatum and substantia nigra) confocal microscopy evaluation of histopathological changes associated with dopaminergic neurodegeneration and glial cell reactivity. Results: Ten weeks after lesion induction, the animals received secretome injections in the substantia nigra pars compacta (SNpc) and striatum (STR). The secretome used was produced from bone marrow mesenchymal stromal cells MSC(M) expanded in a spinner flask (SP) system. Nine weeks later, animals that received the viral vector containing the gene for A53T α-syn and treated with vehicle (Neurobasal-A medium) presented dopaminergic cell loss in the SNpc and denervation in the STR. The treatment with secretome significantly reduced the levels of α-syn in the SNpc and protected the dopaminergic neurons (DAn) within the SNpc and STR. Conclusions: Our results are aligned with previous studies in both α-syn Caenorhabditis elegans models, as well as 6-OHDA rodent model, revealing that secretome exerted a neuroprotective effect. Moreover, these effects were associated with a modulation of microglial reactivity supporting an immunomodulatory role for the factors contained within the secretome. This further supports the development of new studies exploring the effects and the mechanism of action of secretome from MSC(M) against α-syn-induced neurotoxicity.
Language	English
Publishing date	2024-02-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2024.02.008
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Article: Pre-Clinical Assessment of Roflumilast Therapy in a Thoracic Model of Spinal Cord Injury.

Sousa, Carla S / Lima, Rui / Cibrão, Jorge R / Gomes, Eduardo D / Fernandes, Luís S / Pinho, Tiffany S / Silva, Deolinda / Campos, Jonas / Salgado, António J / Silva, Nuno A

Pharmaceutics

2023 Volume 15, Issue 5

Abstract: The failure of axons to regenerate after a spinal cord injury (SCI) remains one of the greatest challenges in neuroscience. The initial mechanical trauma is followed by a secondary injury cascade, creating a hostile microenvironment, which not only is ... ...

Abstract	The failure of axons to regenerate after a spinal cord injury (SCI) remains one of the greatest challenges in neuroscience. The initial mechanical trauma is followed by a secondary injury cascade, creating a hostile microenvironment, which not only is not permissive to regeneration but also leads to further damage. One of the most promising approaches for promoting axonal regeneration is to maintain the levels of cyclic adenosine monophosphate (cAMP), specifically by a phosphodiesterase-4 (PDE4) inhibitor expressed in neural tissues. Therefore, in our study, we evaluated the therapeutic effect of an FDA-approved PDE4 inhibitor, Roflumilast (Rof), in a thoracic contusion rat model. Results indicate that the treatment was effective in promoting functional recovery. Rof-treated animals showed improvements in both gross and fine motor function. Eight weeks post-injury, the animals significantly recovered by achieving occasional weight-supported plantar steps. Histological assessment revealed a significant decrease in cavity size, less reactive microglia, as well as higher axonal regeneration in treated animals. Molecular analysis revealed that IL-10 and IL-13 levels, as well as VEGF, were increased in the serum of Rof-treated animals. Overall, Roflumilast promotes functional recovery and supports neuroregeneration in a severe thoracic contusion injury model and may be important in SCI treatment.
Language	English
Publishing date	2023-05-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15051556
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Article ; Online: Sustained Release of Human Adipose Tissue Stem Cell Secretome from Star-Shaped Poly(ethylene glycol) Glycosaminoglycan Hydrogels Promotes Motor Improvements after Complete Transection in Spinal Cord Injury Rat Model.

Silva, Deolinda / Schirmer, Lucas / Pinho, Tiffany S / Atallah, Passant / Cibrão, Jorge R / Lima, Rui / Afonso, João / B-Antunes, Sandra / Marques, Cláudia R / Dourado, João / Freudenberg, Uwe / Sousa, Rui A / Werner, Carsten / Salgado, António J

Advanced healthcare materials

2023 Volume 12, Issue 17, Page(s) e2202803

Abstract: Adipose tissue-derived stem cells (ASCs) have been shown to assist regenerative processes after spinal cord injury (SCI) through their secretome, which promotes several regenerative mechanisms, such as inducing axonal growth, reducing inflammation, ... ...

Abstract	Adipose tissue-derived stem cells (ASCs) have been shown to assist regenerative processes after spinal cord injury (SCI) through their secretome, which promotes several regenerative mechanisms, such as inducing axonal growth, reducing inflammation, promoting cell survival, and vascular remodeling, thus ultimately leading to functional recovery. However, while systemic delivery (e.g., i.v. [intravenous]) may cause off-target effects in different organs, the local administration has low efficiency due to fast clearance by body fluids. Herein, a delivery system for human ASCs secretome based on a hydrogel formed of star-shaped poly(ethylene glycol) (starPEG) and the glycosaminoglycan heparin (Hep) that is suitable to continuously release pro-regenerative signaling mediators such as interleukin (IL)-4, IL-6, brain-derived neurotrophic factor, glial-cell neurotrophic factor, and beta-nerve growth factor over 10 days, is reported. The released secretome is shown to induce differentiation of human neural progenitor cells and neurite outgrowth in organotypic spinal cord slices. In a complete transection SCI rat model, the secretome-loaded hydrogel significantly improves motor function by reducing the percentage of ameboid microglia and systemically elevates levels of anti-inflammatory cytokines. Delivery of ASC-derived secretome from starPEG-Hep hydrogels may therefore offer unprecedented options for regenerative therapy of SCI.
MeSH term(s)	Rats ; Humans ; Animals ; Glycosaminoglycans ; Delayed-Action Preparations ; Secretome ; Spinal Cord Injuries/drug therapy ; Heparin ; Neural Stem Cells/metabolism ; Spinal Cord ; Adipose Tissue ; Hydrogels ; Polyethylene Glycols/metabolism
Chemical Substances	Glycosaminoglycans ; Delayed-Action Preparations ; Heparin (9005-49-6) ; Hydrogels ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2023-03-04
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202202803
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Zs.A 6966: Show issues

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Article ; Online: Enhanced neuronal differentiation by dynamic piezoelectric stimulation.

Pinho, Tiffany S / Silva, Deolinda / Ribeiro, Jorge Cibrão / Marote, Ana / Lima, Rui / Batista, Salete J / Melo, Rita / Ribeiro, Clarisse / Cunha, Cristiana B / Moreira, Irina S / Lanceros-Mendez, Senentxu / Salgado, António J

Journal of biomedical materials research. Part A

2022 Volume 111, Issue 1, Page(s) 35–44

Abstract: Electroactive smart materials play an important role for tissue regenerative applications. Poly(vinylidene fluoride) (PVDF) is a specific subtype of piezoelectric electroactive material that generates electrical potential upon mechanical stimulation. ... ...

Abstract	Electroactive smart materials play an important role for tissue regenerative applications. Poly(vinylidene fluoride) (PVDF) is a specific subtype of piezoelectric electroactive material that generates electrical potential upon mechanical stimulation. This work focuses on the application of piezoelectric PVDF films for neural differentiation. Human neural precursor cells (hNPCs) are cultured on piezoelectric poled and non-poled β-PVDF films with or without a pre-coating step of poly-d-lysine and laminin (PDL/L). Subsequently, hNPCs differentiation into the neuronal lineage is assessed (MAP2
MeSH term(s)	Humans ; Electricity ; Laminin/pharmacology ; Neural Stem Cells ; Polyvinyls/pharmacology ; Electric Stimulation
Chemical Substances	Laminin ; polyvinylidene fluoride (24937-79-9) ; Polyvinyls
Language	English
Publishing date	2022-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.37443
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Article ; Online: Cerebral Organoids to Study Central Mechanisms of Pain: The Effect of Stem Cell Secretome on Opioid Receptors and Neuroplasticity.

Fernandes, Aline M / Campos, Jonas / Silva, Deolinda / Barata Antunes, Sandra / Lima, Rui / Coelho, Claudio / Marote, Ana M / Leite-Almeida, Hugo / Silva, Nuno / Salgado, António J

Stem cells and development

2022 Volume 31, Issue 19-20, Page(s) 641–657

Abstract: Over 90% of chronic pain (CP) patients receive opioids-based treatments, which led to a public health crisis with lasting impacts on social and economic wellbeing based on opioid addiction. Opioids act through activation of μ (MOR), δ (DOR), and κ (KOR) ... ...

Abstract	Over 90% of chronic pain (CP) patients receive opioids-based treatments, which led to a public health crisis with lasting impacts on social and economic wellbeing based on opioid addiction. Opioids act through activation of μ (MOR), δ (DOR), and κ (KOR) opioid receptors, which are broadly and differentially distributed throughout the brain. Chronic opioid consumption leads to brain changes such as alterations on neurotransmission, dendritic branching, and spine density, as well as an increase in apoptosis. To overcome opioid-related issues, extensive efforts have been made to search for an alternative treatment. Bioactive molecules secreted by stem cells, collectively known as secretome, have shown a positive impact in different pain models. However, there is a lack of studies on the role of secretome in modulating opioid receptors. By using cerebral organoids (CeO), a self-organized, functional, and multicellular 3D structure that resemble the brain, we were able to identify MOR, DOR, and KOR at different stages of maturation. Treatment with secretome increased MOR expression highlighting a possible role in pain signaling mechanisms. Opioid treatments did not impact the expression of neuronal maturation markers but together with secretome, they increased astrogliogenesis. Opioid-treated organoids presented higher dopamine secretion recapitulating an important physiological event after opioid exposure. This work demonstrates that CeO is an important model system for the study of opioid signaling with potential implications to the understanding of basic mechanisms related to pain physiology.
MeSH term(s)	Humans ; Receptors, Opioid/metabolism ; Receptors, Opioid, delta/metabolism ; Receptors, Opioid, mu/metabolism ; Analgesics, Opioid/pharmacology ; Analgesics, Opioid/metabolism ; Organoids/metabolism ; Dopamine/metabolism ; Secretome ; Pain/metabolism ; Neuronal Plasticity ; Stem Cells/metabolism
Chemical Substances	Receptors, Opioid ; Receptors, Opioid, delta ; Receptors, Opioid, mu ; Analgesics, Opioid ; Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2142214-X
ISSN	1557-8534 ; 1547-3287
ISSN (online)	1557-8534
ISSN	1547-3287
DOI	10.1089/scd.2022.0116
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Zs.A 3616: Show issues

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Article ; Online: Pharmacodynamic modelling of the effect of remifentanil using the Pupillary Pain Index.

Vide, Sérgio / Castro, Ana / Antunes, Pedro / Lima, Deolinda / Larson, Merlin / Gambús, Pedro / Amorim, Pedro

Journal of clinical monitoring and computing

2019 Volume 34, Issue 2, Page(s) 319–324

Abstract: Using a targeted controlled infusion of remifentanil during total intravenous anesthesia, we investigated the effect-site concentrations of remifentanil that correlate with different values of the Pupillary Pain Index and which concentrations were ... ...

Abstract	Using a targeted controlled infusion of remifentanil during total intravenous anesthesia, we investigated the effect-site concentrations of remifentanil that correlate with different values of the Pupillary Pain Index and which concentrations were necessary for achieving a Pupillary Pain Index ≤ 4 and its usefulness in titrating opioids. The Pupillary Pain Index was measured in 54 patients prior to surgery under different remifentanil effect-site concentrations and subsequently modeled. One hundred and twenty-eight measurements were taken at different remifentanil concentrations while titrating propofol for a similar depth of hypnosis using a BIS monitor. Our modeled Hill equation revealed a remifentanil of 2.96 ng/mL for a PPI of 4, and the probability model a Ce of 3.22 ng/mL for the probability of 50% of patients achieving a PPI score ≤ 4. For the probability of 80% of patients achieving a PPI score ≤ 4 the Ce of remifentanil was 4.39 ng/mL. We conclude that concentrations of remifentanil that have been shown to suppress movement in response to noxious stimulation correspond to a Pupillary Pain Index ≤ 4.
MeSH term(s)	Adult ; Analgesics, Opioid/administration & dosage ; Analgesics, Opioid/pharmacokinetics ; Analgesics, Opioid/pharmacology ; Anesthesia, Intravenous ; Female ; Humans ; Intraoperative Neurophysiological Monitoring/methods ; Male ; Middle Aged ; Models, Biological ; Nociception/drug effects ; Pain Measurement/methods ; Prospective Studies ; Pupil/drug effects ; Reflex, Pupillary/drug effects ; Remifentanil/administration & dosage ; Remifentanil/pharmacokinetics ; Remifentanil/pharmacology
Chemical Substances	Analgesics, Opioid ; Remifentanil (P10582JYYK)
Language	English
Publishing date	2019-05-22
Publishing country	Netherlands
Document type	Journal Article ; Observational Study
ZDB-ID	1418733-4
ISSN	1573-2614 ; 1387-1307 ; 0748-1977
ISSN (online)	1573-2614
ISSN	1387-1307 ; 0748-1977
DOI	10.1007/s10877-019-00323-x
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Zs.A 2054: Show issues

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Article: Tlx3 Exerts Direct Control in Specifying Excitatory Over Inhibitory Neurons in the Dorsal Spinal Cord.

Monteiro, Filipe A / Miranda, Rafael M / Samina, Marta C / Dias, Ana F / Raposo, Alexandre A S F / Oliveira, Patrícia / Reguenga, Carlos / Castro, Diogo S / Lima, Deolinda

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 642697

Abstract: The spinal cord dorsal horn is a major station for integration and relay of somatosensory information and comprises both excitatory and inhibitory neuronal populations. The homeobox gene Tlx3 acts as a selector gene to control the development of late- ... ...

Abstract	The spinal cord dorsal horn is a major station for integration and relay of somatosensory information and comprises both excitatory and inhibitory neuronal populations. The homeobox gene Tlx3 acts as a selector gene to control the development of late-born excitatory (dILB) neurons by specifying glutamatergic transmitter fate in dorsal spinal cord. However, since Tlx3 direct transcriptional targets remain largely unknown, it remains to be uncovered how Tlx3 functions to promote excitatory cell fate. Here we combined a genomics approach based on chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) and expression profiling, with validation experiments in
Language	English
Publishing date	2021-04-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.642697
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Article ; Online: Accuracy, reliability, validity and limitations of functional and structural magnetic resonance imaging data.

Seixas, Daniela / Lima, Deolinda

Cortex; a journal devoted to the study of the nervous system and behavior

2011 Volume 47, Issue 10, Page(s) 1266–1269

MeSH term(s)	Brain/anatomy & histology ; Brain/physiology ; Data Interpretation, Statistical ; Functional Neuroimaging/instrumentation ; Functional Neuroimaging/standards ; Functional Neuroimaging/utilization ; Humans ; Image Interpretation, Computer-Assisted/standards ; Incidental Findings ; Magnetic Resonance Imaging/standards ; Sensitivity and Specificity
Language	English
Publishing date	2011-11
Publishing country	Italy
Document type	Journal Article
ZDB-ID	280622-8
ISSN	1973-8102 ; 0010-9452
ISSN (online)	1973-8102
ISSN	0010-9452
DOI	10.1016/j.cortex.2011.04.023
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