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Article ; Online: Present and Future of Blood-Based Biomarkers of Alzheimer's Disease: Beyond the Classics.

Mantellatto Grigoli, Marina / Pelegrini, Lucas N C / Whelan, Robert / Cominetti, Marcia R

2024 Volume 1830, Page(s) 148812

Abstract: The field of blood-based biomarkers for Alzheimer's disease (AD) has advanced at an incredible pace, especially after the development of sensitive analytic platforms that can facilitate large-scale screening. Such screening will be important when more ... ...

Abstract	The field of blood-based biomarkers for Alzheimer's disease (AD) has advanced at an incredible pace, especially after the development of sensitive analytic platforms that can facilitate large-scale screening. Such screening will be important when more sophisticated diagnostic methods are scarce and expensive. Thus, blood-based biomarkers can potentially reduce diagnosis inequities among populations from different socioeconomic contexts. This large-scale screening can be performed so that older adults at risk of cognitive decline assessed using these methods can then undergo more complete assessments with classic biomarkers, increasing diagnosis efficiency and reducing costs to the health systems. Blood-based biomarkers can also aid in assessing the effect of new disease-modifying treatments. This paper reviews recent advances in the area, focusing on the following leading candidates for blood-based biomarkers: amyloid-beta (Aβ), phosphorylated tau isoforms (p-tau), neurofilament light (NfL), and glial fibrillary acidic (GFAP) proteins, as well as on new candidates, Neuron-Derived Exosomes contents (NDEs) and Transactive response DNA-binding protein-43 (TDP-43), based on data from longitudinal observational cohort studies. The underlying challenges of validating and incorporating these biomarkers into routine clinical practice and primary care settings are also discussed. Importantly, challenges related to the underrepresentation of ethnic minorities and socioeconomically disadvantaged persons must be considered. If these challenges are overcome, a new time of cost-effective blood-based biomarkers for AD could represent the future of clinical procedures in the field and, together with continued prevention strategies, the beginning of an era with a lower incidence of dementia worldwide.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/diagnosis ; Alzheimer Disease/psychology ; Amyloid beta-Peptides ; Cognitive Dysfunction/diagnosis ; Cohort Studies ; Biomarkers ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins
Language	English
Publishing date	2024-02-17
Publishing country	Netherlands
Document type	Review ; Journal Article
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2024.148812
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Article ; Online: Electrochemical magneto-immunoassay for detection of ADAM10 Alzheimer's biomarker using gold nanoparticles as label.

de Oliveira, Tássia R / Manzine, Patricia R / Cominetti, Márcia R / Leite, Oldair D / Faria, Ronaldo C

Talanta

2023 Volume 266, Issue Pt 2, Page(s) 125042

Abstract: Alzheimer's disease (AD), a neurodegenerative and progressive illness with no known cure, is the most frequent cause of dementia in older adults. Dementia in AD is usually preceded by a stage of cognitive decline known as mild cognitive impairment (MCI). ...

Abstract	Alzheimer's disease (AD), a neurodegenerative and progressive illness with no known cure, is the most frequent cause of dementia in older adults. Dementia in AD is usually preceded by a stage of cognitive decline known as mild cognitive impairment (MCI). MCI has gained attention as an ideal target for prevention and early interventions, considering its reversible characteristic. Here, we propose a magneto-immunoassay based on a low-cost screen-printed electrode for detecting soluble ADAM10 in plasma samples, a potential biomarker for early AD diagnosis. We present a sandwich immunoassay using magnetic beads modified with antibodies to capture ADAM10 from plasma samples and using gold nanoparticles (AuNPs) as an electrochemical label. The assay was designed to accurately detect ADAM10 in diluted plasma with a limit of detection (LoD) of 32.5 pg/mL and a dynamic linear range of 10.0-1000.0 pg/mL. Twenty-three plasma samples from the elderly, including patients with AD, MCI, and healthy subjects (negative control), were analyzed by the magneto-immunoassay and enzyme-linked immunosorbent assay (ELISA), and the ADAM10 levels correlated. This work shows the potential of this protein as a biomarker in the early diagnosis and progression of AD and provides an interesting disposable device with capabilities for applications as point-of-care (PoC) to measure ADAM10 levels.
MeSH term(s)	Aged ; Humans ; Alzheimer Disease/diagnosis ; Gold ; Metal Nanoparticles ; Immunoassay ; Biomarkers ; ADAM10 Protein ; Membrane Proteins ; Amyloid Precursor Protein Secretases
Chemical Substances	Gold (7440-57-5) ; Biomarkers ; ADAM10 protein, human (EC 3.4.24.81) ; ADAM10 Protein (EC 3.4.24.81) ; Membrane Proteins ; Amyloid Precursor Protein Secretases (EC 3.4.-)
Language	English
Publishing date	2023-08-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500969-5
ISSN	1873-3573 ; 0039-9140
ISSN (online)	1873-3573
ISSN	0039-9140
DOI	10.1016/j.talanta.2023.125042
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Article ; Online: Developments in scalable strategies for detecting early markers of cognitive decline.

Whelan, Robert / Barbey, Florentine M / Cominetti, Marcia R / Gillan, Claire M / Rosická, Anna M

Translational psychiatry

2022 Volume 12, Issue 1, Page(s) 473

Abstract: Effective strategies for early detection of cognitive decline, if deployed on a large scale, would have individual and societal benefits. However, current detection methods are invasive or time-consuming and therefore not suitable for longitudinal ... ...

Abstract	Effective strategies for early detection of cognitive decline, if deployed on a large scale, would have individual and societal benefits. However, current detection methods are invasive or time-consuming and therefore not suitable for longitudinal monitoring of asymptomatic individuals. For example, biological markers of neuropathology associated with cognitive decline are typically collected via cerebral spinal fluid, cognitive functioning is evaluated from face-to-face assessments by experts and brain measures are obtained using expensive, non-portable equipment. Here, we describe scalable, repeatable, relatively non-invasive and comparatively inexpensive strategies for detecting the earliest markers of cognitive decline. These approaches are characterized by simple data collection protocols conducted in locations outside the laboratory: measurements are collected passively, by the participants themselves or by non-experts. The analysis of these data is, in contrast, often performed in a centralized location using sophisticated techniques. Recent developments allow neuropathology associated with potential cognitive decline to be accurately detected from peripheral blood samples. Advances in smartphone technology facilitate unobtrusive passive measurements of speech, fine motor movement and gait, that can be used to predict cognitive decline. Specific cognitive processes can be assayed using 'gamified' versions of standard laboratory cognitive tasks, which keep users engaged across multiple test sessions. High quality brain data can be regularly obtained, collected at-home by users themselves, using portable electroencephalography. Although these methods have great potential for addressing an important health challenge, there are barriers to be overcome. Technical obstacles include the need for standardization and interoperability across hardware and software. Societal challenges involve ensuring equity in access to new technologies, the cost of implementation and of any follow-up care, plus ethical issues.
MeSH term(s)	Humans ; Cognitive Dysfunction/diagnosis ; Cognition ; Biomarkers ; Electroencephalography ; Brain
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-11-09
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-022-02237-w
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Article ; Online: A Review of Ruthenium Complexes Activities on Breast Cancer Cells.

Popolin, Cecília P / Cominetti, Márcia R

Mini reviews in medicinal chemistry

2017 Volume 17, Issue 15, Page(s) 1435–1441

Abstract: Background: Cancer is one of the main causes of death worldwide. Breast cancer is the most prevalent type of cancer in women and the leading cause of cancer deaths due to its high metastasis to the lymph nodes, lungs bones and brain. Interactions with ... ...

Abstract	Background: Cancer is one of the main causes of death worldwide. Breast cancer is the most prevalent type of cancer in women and the leading cause of cancer deaths due to its high metastasis to the lymph nodes, lungs bones and brain. Interactions with the stromal microenvironment surrounding tumor cells facilitate tumor cell migration and invasion of tissues and dissemination to other organs, to form metastasis. The development of antitumor metal-based drugs was originated with the discovery of cisplatin, however, its severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as promising antitumor drugs. Conclusion: In this review, we focused on the effects of Ru complexes on breast cancer cells and their impact on different steps of the metastatic process.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Cell Proliferation/drug effects ; Coordination Complexes/chemistry ; Coordination Complexes/pharmacology ; Drug Screening Assays, Antitumor ; Female ; Humans ; Ruthenium/chemistry ; Ruthenium/pharmacology
Chemical Substances	Antineoplastic Agents ; Coordination Complexes ; Ruthenium (7UI0TKC3U5)
Language	English
Publishing date	2017
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2104081-3
ISSN	1875-5607 ; 1389-5575
ISSN (online)	1875-5607
ISSN	1389-5575
DOI	10.2174/1389557517666170206151218
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Article ; Online: Efficacy of Gene Therapy to Restore Cognition in Alzheimer's Disease: A Systematic Review.

Tedeschi, Desyrre V / da Cunha, Anderson F / Cominetti, Márcia R / Pedroso, Renata Valle

Current gene therapy

2021 Volume 21, Issue 3, Page(s) 246–257

Abstract: Background: Alzheimer's disease (AD) is the main cause of dementia and it is a progressive neurogenerative disease characterized by the accumulation of neurofibrillary tangles and senile plaques. There is currently no cure; however, some treatments are ... ...

Abstract	Background: Alzheimer's disease (AD) is the main cause of dementia and it is a progressive neurogenerative disease characterized by the accumulation of neurofibrillary tangles and senile plaques. There is currently no cure; however, some treatments are available to slow down the progression of the disease, including gene therapy, which has been investigated to have great potential for the treatment of AD. Objective: The aim of this review was to identify the efficacy of gene therapy to restore cognition in AD. Methods: A systematic review was carried out using papers published up to May 2020 and available in the Web of Science, Scopus, and Medline/PUBMED databases. Articles were considered for inclusion if they were original researches that investigated the effects of gene therapy on cognition in AD. The methodological quality of the selected studies was evaluated using the Risk of Bias Tool for Animal Intervention Studies (SYRCLE's Rob tool) and the Jadad Scale. Results: Most preclinical studies obtained positive results in improving memory and learning in mice that underwent treatment with gene therapy. On the other hand, clinical studies have obtained inconclusive results related to the delivery methods of the viral vector used in gene therapy. Conclusion: Gene therapy has shown a great potential for the treatment of AD in preclinical trials, but results should be interpreted with caution since preclinical studies presented limitations to predict the efficacy of the treatment outcome in humans.
MeSH term(s)	Aging/genetics ; Alzheimer Disease/therapy ; Animals ; Cognition ; Disease Progression ; Genetic Therapy/methods ; Genetic Vectors/therapeutic use ; Humans ; Memory ; Mice
Language	English
Publishing date	2021-01-22
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2146187-9
ISSN	1875-5631 ; 1566-5232
ISSN (online)	1875-5631
ISSN	1566-5232
DOI	10.2174/1566523221666210120091146
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Article: Metastasis inhibition in breast cancer by targeting cancer cell extravasation.

Cominetti, Márcia R / Altei, Wanessa F / Selistre-de-Araujo, Heloisa Sobreiro

Breast cancer (Dove Medical Press)

2019 Volume 11, Page(s) 165–178

Abstract: The spread of cells from primary tumors toward distant tissues and organs, also known as metastasis, is responsible for most cancer-associated deaths. The metastasis cascade comprises a series of events, characterized by the displacement of tumor cells ( ... ...

Abstract	The spread of cells from primary tumors toward distant tissues and organs, also known as metastasis, is responsible for most cancer-associated deaths. The metastasis cascade comprises a series of events, characterized by the displacement of tumor cells (TCs) from the primary tumor to distant organs by traveling through the bloodstream, and their subsequent colonization. The first step in metastasis involves loss of cell-cell and cell-matrix adhesions, increased invasiveness and migratory abilities, leading to intravasation of TCs into the blood or lymphatic vessels. Stationary TCs must undergo the process of epithelial-mesenchymal transition in order to achieve this migratory and invasive phenotype. Circulating tumor cells that have survived in the circulation and left the blood or lymphatic vessels will reach distant sites where they may stay dormant for many years or grow to form secondary tumors. To do this, cells need to go through the mesenchymal-epithelial transition to revert the phenotype in order to regain epithelial cell-to-cell junctions, grow and become a clinically relevant and detectable tumor mass. This work will review the main steps of the metastatic cascade and describe some strategies to inhibit metastasis by reducing cancer cell extravasation presenting recent studies in the context of breast cancer.
Language	English
Publishing date	2019-04-18
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2520722-2
ISSN	1179-1314
ISSN	1179-1314
DOI	10.2147/BCTT.S166725
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Article ; Online: SSi6 promotes cell death by apoptosis through cell cycle arrest and inhibits migration and invasion of MDA-MB-231 human breast cancer cells.

Luna-Dulcey, Liany / da Silva, James A / Cominetti, Marcia R

Anti-cancer drugs

2019 Volume 31, Issue 1, Page(s) 35–43

Abstract: Triple-negative breast cancer subtype is the most aggressive type of breast cancer due to the lack of specific therapeutic targets, having limited treatment options, low survival prognosis and high recurrence rates. In this work, we describe the effects ... ...

Abstract	Triple-negative breast cancer subtype is the most aggressive type of breast cancer due to the lack of specific therapeutic targets, having limited treatment options, low survival prognosis and high recurrence rates. In this work, we describe the effects of a semisynthetic derivative of [6]-gingerol (6G) called SSi6, produced by the addition of a 2,4-dinitrophenylhydrazine reagent on several aspects of triple-negative breast cancer biology. Human breast cancer cell lines MDA-MB-231 and MCF-10A were used in the experiments. MTT assays were used to detect cell viability. Cell cycle and apoptosis assay were analyzed using flow cytometer Accuri C6 and analysis of proteins as retinoblastoma Rb and kinases Cdk4/6 were analyzed by western blotting. SSi6 induced cytotoxic effects on triple-negative breast cancer cells, with higher selectivity when compared to the non-tumor MCF-10A cells. In addition, SSi6 inhibited migration and invasion of triple-negative breast cancer cells and was able to arrest cell cycle at the G1-phase, mainly by decreasing Cdk4/6-Rb axis levels. Therefore, SSi6 provoked the induction of apoptosis in triple-negative breast cancer cells. SSi6 was more efficient in producing these effects, compared to the original 6G natural product. This study may contribute to a better understanding of the effects of natural and semisynthetic products on the in-vitro metastatic processes in the MDA-MB-231 triple-negative breast cancer cell line. Additional, it can be useful to understand the effects of chemical modifications on already effective natural compounds aiming at the improvement of their bioactive properties, such as in the increase of the cytotoxic selectivity against tumor cells, compared to non-tumor ones.
MeSH term(s)	Apoptosis/drug effects ; Catechols/chemistry ; Catechols/pharmacology ; Cell Line, Tumor ; Cell Movement/drug effects ; Fatty Alcohols/chemistry ; Fatty Alcohols/pharmacology ; Female ; G1 Phase Cell Cycle Checkpoints/drug effects ; Humans ; Neoplasm Invasiveness ; Phenylhydrazines/chemistry ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	Catechols ; Fatty Alcohols ; Phenylhydrazines ; 2,4-dinitrophenylhydrazine (1N39KD7QPJ) ; gingerol (925QK2Z900)
Language	English
Publishing date	2019-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1065301-6
ISSN	1473-5741 ; 0959-4973
ISSN (online)	1473-5741
ISSN	0959-4973
DOI	10.1097/CAD.0000000000000826
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Article ; Online: Cytotoxic activity of Ru(II)/DPEPhos/N,S-mercapto complexes (DPEPhos = bis-[(2-diphenylphosphino)phenyl]ether).

Grawe, Gregory F / Oliveira, Katia M / Leite, Celisnolia M / de Oliveira, Tamires D / Costa, Analu R / Moraes, Carlos A F / Honorato, João / Cominetti, Marcia R / Castellano, Eduardo E / Correa, Rodrigo S / Machado, Sérgio P / Batista, Alzir A

Journal of inorganic biochemistry

2023 Volume 244, Page(s) 112204

Abstract: We report here on three new ruthenium(II) complexes, [Ru(DPEPhos)(mtz)(bipy)] ... ...

Abstract	We report here on three new ruthenium(II) complexes, [Ru(DPEPhos)(mtz)(bipy)]PF
MeSH term(s)	Humans ; Cell Line, Tumor ; Coordination Complexes/pharmacology ; Coordination Complexes/chemistry ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Molecular Structure ; Ethers ; Ruthenium/chemistry
Chemical Substances	Coordination Complexes ; Antineoplastic Agents ; Ethers ; Ruthenium (7UI0TKC3U5)
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	162843-4
ISSN	1873-3344 ; 0162-0134
ISSN (online)	1873-3344
ISSN	0162-0134
DOI	10.1016/j.jinorgbio.2023.112204
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Zs.B 1730: Show issues

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Article ; Online: Photobiomodulation of a flowable matrix in a human skin ex vivo model demonstrates energy-based enhancement of engraftment integration and remodeling.

Neves, Lia M G / Parizotto, Nivaldo A / Cominetti, Marcia R / Bayat, Ardeshir

Journal of biophotonics

2018 Volume 11, Issue 9, Page(s) e201800077

Abstract: The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the ... ...

Abstract	The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice.
MeSH term(s)	Collagen/metabolism ; Glycosaminoglycans/metabolism ; Humans ; Low-Level Light Therapy ; Skin/cytology ; Skin/metabolism ; Skin/radiation effects ; Tissue Engineering/methods ; Tissue Survival/radiation effects ; Wound Healing/radiation effects
Chemical Substances	Glycosaminoglycans ; Collagen (9007-34-5)
Language	English
Publishing date	2018-05-29
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2390063-5
ISSN	1864-0648 ; 1864-063X
ISSN (online)	1864-0648
ISSN	1864-063X
DOI	10.1002/jbio.201800077
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Zs.A 6723: Show issues

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Article: Label-free evaluation of small-molecule–protein interaction using magnetic capture and electrochemical detection

Uliana, Carolina V / de Oliveira, Tássia R / Cominetti, Márcia R / Faria, Ronaldo C

Analytical and bioanalytical chemistry. 2019 Apr., v. 411, no. 10

2019

Abstract: The evaluation of interaction between small molecules and protein is an important step in the discovery of new drugs and to study complex biological systems. In this work, an alternative method was presented to evaluate small-molecule–protein interaction ...

Abstract	The evaluation of interaction between small molecules and protein is an important step in the discovery of new drugs and to study complex biological systems. In this work, an alternative method was presented to evaluate small-molecule–protein interaction by using ligand capture by protein-coated magnetic particles (MPs) and disposable electrochemical cells. The interaction study was conducted using [10]-gingerol from ginger rhizome and a transmembrane protein αVβ3 integrin. Initially, the electrochemical behavior of the natural compound [10]-gingerol was evaluated with the disposable carbon-based electrodes and presented an irreversible oxidation process controlled by diffusion. The analytical curve for [10]-gingerol was obtained in the range of 1.0 to 20.0 μmol L−1, with limit of detection of 0.26 μmol L−1. Then MPs coated with αVβ3 integrin were incubated with standard solutions and extracts of ginger rhizome for [10]-gingerol capture and separation. The bioconjugate obtained was dropped to the disposable electrochemical cells, keeping a permanent magnet behind the working electrode, and the binding process was evaluated by the electrochemical detection of [10]-gingerol. The assay method proposed was also employed to calculate the [10]-gingerol–αVβ3 integrin association constant, which was calculated as 4.3 × 107 M−1. The method proposed proved to be a good label-free alternative to ligand–protein interaction studies. Graphical abstract ᅟ
Keywords	detection limit ; electrochemistry ; electrodes ; ginger ; integrins ; ligands ; magnetic materials ; magnetism ; new drugs ; oxidation ; rhizomes ; transmembrane proteins
Language	English
Dates of publication	2019-04
Size	p. 2111-2119.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-019-01636-1
Database	NAL-Catalogue (AGRICOLA)

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