scholarly journals A Novel Treatment for Glomerular Disease: Targeting the Activated Macrophage Folate Receptor with a Trojan Horse Therapy in Rats

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2113
Author(s):  
Gabriela E. Garcia ◽  
Yingjuan J. Lu ◽  
Luan D. Truong ◽  
Carlos A. Roncal-Jiménez ◽  
Makoto Miyazaki ◽  
...  
Keyword(s):  
Folic Acid ◽  
Crescentic Glomerulonephritis ◽  
Inflammatory Diseases ◽  
Folate Receptor ◽  
Kidney Injury ◽  
Macrophage Population ◽  
Novel Treatment ◽  
M1 Macrophage ◽  
Kidney Protection ◽  
Activated Macrophage

Since activated macrophages express a functional folate receptor β (FRβ), targeting this macrophage population with folate-linked drugs could increase selectivity to treat inflammatory diseases. Using a macrophage-mediated anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) in WKY rats, we investigated the effect of a novel folic acid-aminopterin (AMT) conjugate (EC2319) designed to intracellularly deliver AMT via the FR. We found that treatment with EC2319 significantly attenuated kidney injury and preserved renal function. Kidney protection with EC2319 was blocked by a folate competitor, indicating that its mechanism of action was specifically FRβ-mediated. Notably, treatment with methotrexate (MTX), another folic acid antagonist related to AMT, did not protect from kidney damage. EC2319 reduced glomerular and interstitial macrophage infiltration and decreased M1 macrophage recruitment but not M2 macrophages. The expression of CCL2 and the pro-fibrotic cytokine TGF-β were also reduced in nephritic glomeruli with EC2319 treatment. In EC2319-treated rats, there was a significant decrease in the deposition of collagens. In nephritic kidneys, FRβ was expressed on periglomerular macrophages and macrophages present in the crescents, but its expression was not observed in normal kidneys. These data indicate that selectively targeting the activated macrophage population could represent a novel means for treating anti-GBM GN and other acute crescentic glomerulonephritis.

scholarly journals Pharmacokinetic Properties of 68Ga-labelled Folic Acid Conjugates: Improvement Using HEHE Tag

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2712
Author(s):  
Anton Larenkov ◽  
Marat Rakhimov ◽  
Kristina Lunyova ◽  
Olga Klementyeva ◽  
Alesya Maruk ◽  
...  
Keyword(s):  
Folic Acid ◽  
Inflammatory Diseases ◽  
Folate Receptor ◽  
Renal Tissue ◽  
Laboratory Animals ◽  
Biodistribution Studies ◽  
Pharmacokinetic Properties ◽  
Normal Laboratory

The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic acid-based radioconjugate. FR is often overexpressed by cells of epithelial tumors, including tumors of ovary, cervix, endometrium, lungs, kidneys, etc. In healthy tissues, FR can be found in small numbers by the epithelial cells, mainly in the kidneys. Extremely high undesired accumulation of the folate radioconjugates in the renal tissue is a main drawback of FR-targeting concept. In the course of this work, we aimed to reduce the undesirable accumulation of folate radioconjugates in the kidneys by introducing a histidine/glutamic acid tag into their structure. Two folic acid based compounds were synthesized: NODAGA-1,4-butanediamine-folic acid (FA-I, as control) and NODAGA-[Lys-(HE)2]-folic acid (FA-II) which contains a (His-Glu)2 fragment. In vitro studies with FR (+) cells (KB and others) showed that both compounds have specificity for FR. Introduction of (HE)2-tag does not affect FR binding ability of the conjugates. In vivo biodistribution studies with normal laboratory animals, as well as with KB tumor bearing animals, were carried out. The results showed that introduction of the (HE)2 tag into the structure of folate radioconjugates can significantly reduce the accumulation of these compounds in non-target tissues and important organs (the accumulation in the kidneys is reduced 2–4 times), leaving the accumulation in tumor at least at the same level, and even increasing it.

Folic acid-conjugated green luminescent carbon dots as a nanoprobe for identifying folate receptor-positive cancer cells

Talanta ◽  
2018 ◽  
Vol 183 ◽  
pp. 39-47 ◽  
Author(s):  
Junli Zhang ◽  
Xuewei Zhao ◽  
Ming Xian ◽  
Chuan Dong ◽  
Shaomin Shuang
Keyword(s):  
Folic Acid ◽  
Cancer Cells ◽  
Carbon Dots ◽  
Folate Receptor

Graphene Oxide/Perylene-Aniline Electrochemiluminescence Platform for Protein Detection Based on Molecule Recognition

2021 ◽  
Author(s):  
Peng Yin ◽  
Wei Zhang ◽  
Lei Shang ◽  
Rong-Na Ma ◽  
Liping Jia ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Folic Acid ◽  
Small Molecule ◽  
Folate Receptor ◽  
Protein Detection ◽  
Single Strand ◽  
Molecule Recognition

Most biosensors for protein folate receptor(FR) detection based on small molecule folic acid(FA) recognition usually introduced FA linked single strand DNA(FA-ssDNA) and nuclease to promote sensitivity, which increased expenses and...

Tanshinone IIA Protects Against Folic Acid-Induced Acute Kidney Injury

2016 ◽  
Vol 44 (04) ◽  
pp. 737-753 ◽  
Author(s):  
Chunming Jiang ◽  
Wei Zhu ◽  
Qiuyuan Shao ◽  
Xiang Yan ◽  
Bo Jin ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Folic Acid ◽  
Salvia Miltiorrhiza ◽  
Kidney Injury ◽  
Inflammatory Cells ◽  
Tanshinone Iia ◽  
Nuclear Antigen ◽  
Local Inflammatory Response ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Injured Kidney

Tanshinone IIA is a diterpene extracted from Salvia miltiorrhiza, a popular and safe herb medicine that has been widely used in China and other Asian countries. Previous studies have demonstrated the pleiotropic effects of Tanshinone IIA on many disease treatments via its antitoxicity, anti-inflammation, anti-oxidative stress, as well as antifibrosis activities. However, its effect on acute kidney injury (AKI) has not been fully investigated. Here, we show for the first time that systemic administration of Tanshinone IIA can lead to improved kidney function in folic acid-induced kidney injury mice. In the acute phase of AKI, Tanshinone IIA attenuated renal tubular epithelial injury, as determined by histologic changes and the detection of Neutrophil gelatinase-associated lipocalin (NGAL) in the kidney and urine. Additionally, Tanshinone IIA treatment resulted in elevated proliferating cell nuclear antigen (PCNA) expression and decreased inflammatory cells infiltration as well as chemokine expression, suggesting that Tanshinone IIA promoted renal repair following AKI and inhibited local inflammatory response in the injured kidney. This led to decreased long-term fibrosis in the injured kidney, characterized by less accumulation of fibronectin and collagen I in tubulointerstitium. Taken together, these results suggest that Tanshinone IIA may represent a potential approach for AKI treatment.

scholarly journals Early Implementation of Veno-Venous Hemofiltration and Use of Rotational Atherectomy in a Patient with ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock- case report.

2020 ◽  
Author(s):  
Monika Durak ◽  
Marek Tomala ◽  
Bartłomiej Nawrotek ◽  
Andrzej Machnik ◽  
Jacek Legutko
Keyword(s):  
Myocardial Infarction ◽  
Acute Kidney Injury ◽  
Case Report ◽  
Cardiogenic Shock ◽  
Right Ventricular ◽  
Kidney Injury ◽  
Novel Treatment ◽  
Early Implementation ◽  
Right Ventricular Myocardial Infarction ◽  
St Elevation

We report a patient with cardiogenic shock (CS) in the course of acute right ventricular myocardial infarction (MI). Our case highlights the use of continuous veno-venous hemofiltration as a novel treatment option for acute kidney injury in the setting of CS and the use of rotational_atherectomy in patients with MI.

scholarly journals Evaluating biological activity of folic acid-modified and 10-hydroxycamptothecin-loaded mesoporous silica nanoparticles

2021 ◽  
Author(s):  
Mei-Xia Zhao ◽  
Di-Feng Chen ◽  
Xue-Jie Zhao ◽  
Lin-Song Li ◽  
Yong-Fang Liu
Keyword(s):  
Folic Acid ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Folate Receptor ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carriers ◽  
Transmission Electron ◽  
Before And After ◽  
Drug Efficiency

Targeted nanocarrier can selectively deliver anti-tumor drugs to cancer sites improving drug efficiency. Accordingly, a targeted nanocarrier (MSN-FA) was synthesized based on folic acid (FA) modified mesoporous silica nanoparticles (MSNs). These loaded with 10-hydroxycamptothecin (HCPT) to obtain the nano-drug MSN-FA@HCPT. These nanocarriers were characterized by transmission electron microscopy (TEM), zeta potential, ultraviolet-visible spectroscopy (UV-Vis), fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). Notably, the nanocarriers were nearly spherical before and after loading HCPT and exhibited good dispersibility. Also, folate receptor (FR) over-expressing HeLa cells and FR deficient HepG2 cells were used to evaluate in vitro cellular uptake and cytotoxicity of MSN-FA@HCPT and MSN@HCPT. Interestingly, FA-modified nanocarriers enhanced the cytotoxicity of HCPT by improving drug targeting to tumor cells. Also, apoptotic and mitochondrial membrane potential (MMP) reducing effects of MSN-FA@HCPT were more prominent than the MSNs without FA modification. MSN-FA@HCPT can be excellent drug carriers with profound biomedical applications.

scholarly journals Multiparametric MRI detects longitudinal evolution of folic acid-induced nephropathy in mice

2018 ◽  
Vol 315 (5) ◽  
pp. F1252-F1260 ◽  
Author(s):  
Kai Jiang ◽  
Tristan A. Ponzo ◽  
Hui Tang ◽  
Prasanna K. Mishra ◽  
Slobodan I. Macura ◽  
...  
Keyword(s):  
Folic Acid ◽  
Interstitial Fibrosis ◽  
Magnetization Transfer ◽  
Kidney Injury ◽  
Multiparametric Mri ◽  
Magnetization Transfer Ratio ◽  
Kidney Volume ◽  
Kidney Size ◽  
Functional Changes

The rodent model of folic acid (FA)-induced acute kidney injury (AKI) provides a useful model for studying human AKI, but little is known about longitudinal changes in renal hemodynamics and evolution of renal fibrosis in vivo. In this work, we aimed to longitudinally assess renal structural and functional changes using multiparametric magnetic resonance imaging (MRI). Ten adult mice were injected with FA, after which a multiparametric MRI was used to measure kidney volume, hypoxia index R2*, magnetization transfer ratio (MTR), perfusion, T1, and glomerular filtration rate (GFR) at 2 wk posttreatment. Then five mice were euthanized for histology, and the other five underwent MRI again at 4 wk, followed by histology. Control mice ( n = 5) were injected with vehicle and studied with MRI at 2 wk. Trichrome and hematoxylin-eosin staining were performed to assess FA-induced tissue injuries. Whereas kidney size and oxygenation showed progressive deterioration, a transient impairment in renal perfusion and normalized GFR slightly improved by 4 wk. Kidney fluid content, as reflected by T1, was prominent at 2 wk and tended to regress at 4 wk, consistent with observed tubular dilation. Trichrome staining revealed patchy necrosis and mild interstitial fibrosis at 2 wk, which exacerbated at 4 wk. MTR detected increased fibrosis at 4 wk. In conclusion, multiparametric MRI captured the longitudinal progression in kidney damage evolving within the first month after treatment with folic acid and may provide a useful tool for assessment of therapeutic strategies.

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