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Article ; Online: Power-Doppler Ultrasonic Imaging of Peripheral Perfusion in Diabetic Mice.

Babaei, Somaye / Dobrucki, Lawrence W / Insana, Michael F

IEEE transactions on bio-medical engineering

2024 Volume PP

Abstract: Objective: We explored the capabilities of power-Doppler ultrasonic (PD-US) imaging without contrast enhancement for monitoring changes in muscle perfusion over time.: Methods: Ischemic recovery was observed in healthy and type II diabetic male and ... ...

Abstract	Objective: We explored the capabilities of power-Doppler ultrasonic (PD-US) imaging without contrast enhancement for monitoring changes in muscle perfusion over time. Methods: Ischemic recovery was observed in healthy and type II diabetic male and female mice with and without exercise. In separate studies, perfusion was measured during and after 5-min ischemic periods and during four-week recovery periods following irreversible femoral ligation. A goal was to assess how well PD-US estimates tracked the diabetic-related changes in endothelial function that influenced perfusion. Results: The average perfusion recovery time following femoral ligation increased 47% in diabetic males and 74% in diabetic females compared with non-diabetic mice. Flow-mediated dilation in conduit arteries and the reactive hyperemia index in resistive vessels each declined by one half in sedentary diabetic mice compared with sedentary non-diabetic mice. We found that exercise reduced the loss of endothelial function from diabetes in both sexes. The reproducibility of perfusion measurements was limited primarily by our ability to select the same region in muscle and to effectively filter tissue clutter. Conclusions/significance: PD-US measurements can precisely follow site-specific changes in skeletal muscle perfusion related to diabetes over time, which fills the need for techniques capable of regularly monitoring atherosclerotic changes leading to ischemic vascular pathologies.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	160429-6
ISSN	1558-2531 ; 0018-9294
ISSN (online)	1558-2531
ISSN	0018-9294
DOI	10.1109/TBME.2024.3373254
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Article ; Online: Coordination Chemistry of Sulfur-Containing Bifunctional Chelators: Toward

Yu, Zhengxin / Blade, Glenn / Bouley, Bailey S / Dobrucki, Iwona T / Dobrucki, Lawrence W / Mirica, Liviu M

Inorganic chemistry

2023 Volume 62, Issue 50, Page(s) 20820–20833

Abstract: The broader utilization ... ...

Abstract	The broader utilization of
MeSH term(s)	Humans ; Chelating Agents/chemistry ; Alzheimer Disease/diagnostic imaging ; Copper ; Copper Radioisotopes/chemistry ; Ligands ; Positron-Emission Tomography/methods
Chemical Substances	Chelating Agents ; Copper (789U1901C5) ; Copper Radioisotopes ; Ligands
Language	English
Publishing date	2023-12-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1484438-2
ISSN	1520-510X ; 0020-1669
ISSN (online)	1520-510X
ISSN	0020-1669
DOI	10.1021/acs.inorgchem.3c02929
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Article ; Online: The Impact of LY487379 or CDPPB on eNOS Expression in the Mouse Brain and the Effect of Joint Administration of Compounds with NO

Płoska, Agata / Siekierzycka, Anna / Cieślik, Paulina / Dobrucki, Lawrence W / Kalinowski, Leszek / Wierońska, Joanna M

Molecules (Basel, Switzerland)

2024 Volume 29, Issue 3

Abstract: The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer's disease (AD). Positive ... ...

Abstract	The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer's disease (AD). Positive allosteric modulators (PAMs) of metabotropic glutamate (mGlu) receptors were shown to be effective procognitive compounds, but little is known about their impact on eNOS expression and stability. Here, we investigated the influence of the acute and chronic administration of LY487379 or CDPPB (mGlu2 and mGlu5 PAMs), on eNOS expression in the mouse brain and the effect of the joint administration of the ligands with nitric oxide (NO) releasers, spermineNONOate or DETANONOate, in different combinations of doses, on MK-801- or scopolamine-induced amnesia in the novel object recognition (NOR) test. Our results indicate that both compounds provoked eNOS monomer formation, and CDPPB at a dose of 5 mg/kg exaggerated the effect of MK-801 or scopolamine. The coadministration of spermineNONOate or DETANONOate enhanced the antiamnesic effect of CDPPB or LY487379. The best activity was observed for ineffective or moderate dose combinations. The results indicate that treatment with mGluR2 and mGluR5 PAMs may be burdened with the risk of promoting eNOS uncoupling through the induction of dimer dissociation. Administration of the lowest possible doses of the compounds with NO
MeSH term(s)	Mice ; Animals ; Dizocilpine Maleate/pharmacology ; Nitric Oxide/pharmacology ; Scopolamine/pharmacology ; Nitric Oxide Synthase Type III ; Cognitive Dysfunction/drug therapy ; Brain ; Allosteric Regulation ; Nitroso Compounds ; Pyrazoles ; Benzamides ; Sulfonamides ; Pyridines
Chemical Substances	Dizocilpine Maleate (6LR8C1B66Q) ; N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine ; 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide ; Nitric Oxide (31C4KY9ESH) ; Scopolamine (DL48G20X8X) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (146724-94-9) ; Nitroso Compounds ; Pyrazoles ; Benzamides ; Sulfonamides ; Pyridines
Language	English
Publishing date	2024-01-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules29030627
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Article ; Online: Targeted Imaging of Abdominal Aortic Aneurysm: Biology Over Structure.

Dobrucki, Lawrence W / Sinusas, Albert J

Circulation. Cardiovascular imaging

2020 Volume 13, Issue 3, Page(s) e010495

MeSH term(s)	Aorta, Abdominal ; Aortic Aneurysm, Abdominal ; Humans ; Inflammation ; Positron-Emission Tomography ; Receptors, CCR2
Chemical Substances	CCR2 protein, human ; Receptors, CCR2
Language	English
Publishing date	2020-03-13
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2435045-X
ISSN	1942-0080 ; 1941-9651
ISSN (online)	1942-0080
ISSN	1941-9651
DOI	10.1161/CIRCIMAGING.120.010495
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Zs.A 6743: Show issues

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Article ; Online: Molecular Imaging and Nanotechnology-Emerging Tools in Diagnostics and Therapy.

Woźniak, Marcin / Płoska, Agata / Siekierzycka, Anna / Dobrucki, Lawrence W / Kalinowski, Leszek / Dobrucki, Iwona T

International journal of molecular sciences

2022 Volume 23, Issue 5

Abstract: Personalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular ... ...

Abstract	Personalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular imaging (MI) enables advanced insight into molecule interactions and disease pathology, improving the process of diagnosis and therapy and, for that reason, plays a crucial role in personalized medicine. Nanoparticles are widely used in MI techniques due to their size, high surface area to volume ratio, and multifunctional properties. After conjugation to specific ligands and drugs, nanoparticles can transport therapeutic compounds directly to their area of action and therefore may be used in theranostics-the simultaneous implementation of treatment and diagnostics. This review summarizes different MI techniques, including optical imaging, ultrasound imaging, magnetic resonance imaging, nuclear imaging, and computed tomography imaging with theranostics nanoparticles. Furthermore, it explores the potential use of constructs that enables multimodal imaging and track diseases in real time.
MeSH term(s)	Drug Delivery Systems ; Humans ; Molecular Imaging/methods ; Multimodal Imaging ; Nanoparticles/therapeutic use ; Nanotechnology
Language	English
Publishing date	2022-02-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23052658
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Article: RAGE as a Novel Biomarker for Prostate Cancer: A Systematic Review and Meta-Analysis.

Applegate, Catherine C / Nelappana, Michael B / Nielsen, Elaine A / Kalinowski, Leszek / Dobrucki, Iwona T / Dobrucki, Lawrence W

Cancers

2023 Volume 15, Issue 19

Abstract: The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta- ... ...

Abstract	The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects. A multi-database search was used to identify original clinical and preclinical research articles examining RAGE expression in PCa. After screening and review, nine clinical and six preclinical articles were included. The associations of RAGE differentiating benign prostate hyperplasia (BPH) or normal prostate from PCa and between tumor grades were estimated using odds ratios (ORs) and associated 95% confidence intervals (CI). Pooled estimates were calculated using random-effect models due to study heterogeneity. The clinical meta-analysis found that RAGE expression was highly likely to be increased in PCa when compared to BPH or normal prostate (OR: 11.3; 95% CI: 4.4-29.1) and that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5; 95% CI: 1.8-3.4). In addition, meta-analysis estimates of preclinical studies performed by albatross plot generation found robustly positive associations among RAGE expression/activation and PCa growth and metastatic potential. This review demonstrates that RAGE expression is strongly tied to PCa progression and can serve as an effective diagnostic target to differentiate between healthy prostate, low-grade PCa, and high-grade PCa, with potential theragnostic applications.
Language	English
Publishing date	2023-10-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15194889
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Article ; Online: Receptor for advanced glycation end-products: Biological significance and imaging applications.

Dobrucki, Iwona T / Miskalis, Angelo / Nelappana, Michael / Applegate, Catherine / Wozniak, Marcin / Czerwinski, Andrzej / Kalinowski, Leszek / Dobrucki, Lawrence W

Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology

2023 Volume 16, Issue 1, Page(s) e1935

Abstract: The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand ... ...

Abstract	The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.
MeSH term(s)	Humans ; Glycation End Products, Advanced/metabolism ; Receptor for Advanced Glycation End Products/metabolism ; Maillard Reaction ; Diabetes Mellitus/metabolism ; Inflammation
Chemical Substances	Glycation End Products, Advanced ; Receptor for Advanced Glycation End Products
Language	English
Publishing date	2023-11-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2502698-7
ISSN	1939-0041 ; 1939-5116
ISSN (online)	1939-0041
ISSN	1939-5116
DOI	10.1002/wnan.1935
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Zs.A 6781: Show issues

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Article ; Online: Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.

Janaszak-Jasiecka, Anna / Płoska, Agata / Wierońska, Joanna M / Dobrucki, Lawrence W / Kalinowski, Leszek

Cellular & molecular biology letters

2023 Volume 28, Issue 1, Page(s) 21

Abstract: Nitric oxide (NO) is one of the most important molecules released by endothelial cells, and its antiatherogenic properties support cardiovascular homeostasis. Diminished NO bioavailability is a common hallmark of endothelial dysfunction underlying the ... ...

Abstract	Nitric oxide (NO) is one of the most important molecules released by endothelial cells, and its antiatherogenic properties support cardiovascular homeostasis. Diminished NO bioavailability is a common hallmark of endothelial dysfunction underlying the pathogenesis of the cardiovascular disease. Vascular NO is synthesized by endothelial nitric oxide synthase (eNOS) from the substrate L-arginine (L-Arg), with tetrahydrobiopterin (BH
MeSH term(s)	Humans ; Nitric Oxide Synthase Type III/metabolism ; Endothelial Cells/metabolism ; Vascular Diseases ; Superoxides ; Oxidative Stress
Chemical Substances	Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Superoxides (11062-77-4)
Language	English
Publishing date	2023-03-09
Publishing country	England
Document type	Letter
ZDB-ID	2108724-6
ISSN	1689-1392 ; 1689-1392
ISSN (online)	1689-1392
ISSN	1689-1392
DOI	10.1186/s11658-023-00423-2
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Article ; Online: Molecular Imaging and Nanotechnology—Emerging Tools in Diagnostics and Therapy

Marcin Woźniak / Agata Płoska / Anna Siekierzycka / Lawrence W. Dobrucki / Leszek Kalinowski / Iwona T. Dobrucki

International Journal of Molecular Sciences, Vol 23, Iss 2658, p

2022 Volume 2658

Abstract	Personalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular imaging (MI) enables advanced insight into molecule interactions and disease pathology, improving the process of diagnosis and therapy and, for that reason, plays a crucial role in personalized medicine. Nanoparticles are widely used in MI techniques due to their size, high surface area to volume ratio, and multifunctional properties. After conjugation to specific ligands and drugs, nanoparticles can transport therapeutic compounds directly to their area of action and therefore may be used in theranostics—the simultaneous implementation of treatment and diagnostics. This review summarizes different MI techniques, including optical imaging, ultrasound imaging, magnetic resonance imaging, nuclear imaging, and computed tomography imaging with theranostics nanoparticles. Furthermore, it explores the potential use of constructs that enables multimodal imaging and track diseases in real time.
Keywords	molecular imaging ; theranostics ; personalized medicine ; nanotechnology ; nanoparticles ; imaging modalities ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh.

Płoska, Agata / Wozniak, Marcin / Hedhli, Jamila / Konopka, Christian J / Skondras, Antonios / Matatov, Sarah / Stawarz, Andrew / Schuh, Sarah / Czerwinski, Andrzej / Dobrucki, Lawrence W / Kalinowski, Leszek / Dobrucki, Iwona T

International journal of molecular sciences

2023 Volume 24, Issue 24

Abstract: As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 ... ...

Abstract	As a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after incubation with both DOX and BC was significantly increased (~100%) compared to the control. Treatment with DOX altered the potential of MCF-7 cells to form colonies; however, coincubation with BC did not affect this process. In vivo, PET-CT imaging showed that combined treatment of DOX and BC induced a significant reduction in both metabolic activity (29%) and angiogenesis (32%). Both DOX and BC treatments inhibited tumor growth by 20% and 12%, respectively, and combined by 57%, vs. control. We successfully demonstrated that BC increases cytotoxic effects of DOX, resulting in a significant reduction in tumor size. Further studies regarding drug transport and tumor growth biomarkers are necessary to establish the underlying mechanism and potential clinical use of BC in breast cancer patients.
MeSH term(s)	Humans ; Female ; Cimicifuga ; Positron Emission Tomography Computed Tomography ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Antineoplastic Agents/therapeutic use ; MCF-7 Cells ; Cell Line, Tumor
Chemical Substances	Doxorubicin (80168379AG) ; Antineoplastic Agents
Language	English
Publishing date	2023-12-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242417506
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