Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients
Abstract
:1. Introduction
2. Results
2.1. Hfn-BDC Nanoformulation
2.2. RNA-Seq Differentially Expressed mRNAs and lncRNAs
- AD NT vs. CTR NT;
- AD BDC-HFn vs. CTR BDC-HFn;
- AD NT vs. AD BDC-HFn;
- AD BDC-HFn vs. CTR NT;
- CTR NT vs. CTR BDC-HFn.
2.2.1. AD NT vs. CTR NT
2.2.2. AD NT vs. AD BDC-HFn
2.3. Validation of Deregulated Coding and Noncoding Genes
2.4. mRNA Pathway Analysis
2.4.1. AD NT vs. CTR NT
2.4.2. AD NT vs. AD Hfn-BDC
2.4.3. AD BDC-HFn vs. CTR BDC-HFn
2.4.4. AD BDC-HFn vs. CTR NT and CTR NT vs. CTR BDC-HFn
2.5. BDC-HFn Penetration across a BBB In Vitro Model
3. Discussion
4. Materials and Methods
4.1. Nanoformulation and Characterization of BDC-HFn
4.1.1. HFn Loading with Bisdemethoxycurcumin (BDC)
4.1.2. BDC-HFn Nanoparticles Characterization by Transmission Electron Microscope and Dynamic Light Scattering
4.1.3. Determination of Drug Loading Efficiency and Stability of BDC-HFn
4.1.4. Raman Spectroscopy
4.2. Blood Brain Barrier Model (BBB)
4.3. Cell Binding Assay
4.4. Endothelial Cells Viability Assay
4.5. BDC Measurement by UPLC/MS-MS
4.6. Study Subjects
4.7. PBMCs Isolation, Treatment, and RNA Extraction
- -
- PBMCs isolated from AD patients not treated (AD NT);
- -
- PBMCs isolated from AD patients treated with BDC-HFn (AD BDC-HFn);
- -
- PBMCs isolated from Controls not treated (CTR NT);
- -
- PBMCs isolated from controls treated with BDC-HFn (CTR BDC-HFn).
4.8. Libraries Preparation for RNA-Seq and Bioinformatic Data Analysis
4.9. Pathway Analysis
4.10. Real-Time PCR
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Upregulated | Downregulated | Total RNAs | |||
---|---|---|---|---|---|
mRNA | lncRNA | mRNA | lncRNA | ||
AD NT vs. CTR NT | 333 | 11 | 234 | 52 | 630 |
AD NT vs. AD BDC-HFn | 1419 | 88 | 952 | 58 | 2517 |
AD BDC-HFn vs. CTR BDC-HFn | 29 | 7 | 52 | 10 | 98 |
AD Hfn-BDC vs. CTR NT | 151 | 30 | 566 | 24 | 771 |
CTR NT vs. CTR BDC-HFn | 164 | 26 | 724 | 22 | 936 |
Most Deregulated Genes in AD-NT Group Compared to CTR-NT | ||
---|---|---|
Gene | Fold Change | Role in AD |
CXCL5 | −5.28042797835226 | monocytes migrating from blood to brain in AD patients [48] |
CD1E | −3.76621256916995 | CD1A is involved in longitudinal changes AD phenotypes [49] |
IL12RB2 | −2.36344776700486 | associated with cognitive aging [50] |
IL18RAP | −1.994385464 | associated to Tau concentration in CSF of AD patients [51] |
LILRA6 | 1.930851051 | expressed in monocyte, function unclear [52] |
LILRB5 | 4.048756658 | expressed in monocyte, function unclear [52] |
HLA-DRB6 | 3.84178295 | associated to late onset AD [53] |
TLR5 | 3.589139449 | may regulate Aβ clearance [54] |
CTRs | AD | |
Recruited subjects | 15 | 15 |
Age (mean ± SD) | 56.1 ± 5.2 | 74.4 ± 8.8 |
Males % | 43% | 47% |
Females % | 57% | 53% |
MMSE | 29.625 ± 0.74 | 18.5 ± 3.88 |
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Gagliardi, S.; Truffi, M.; Tinelli, V.; Garofalo, M.; Pandini, C.; Cotta Ramusino, M.; Perini, G.; Costa, A.; Negri, S.; Mazzucchelli, S.; et al. Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients. Int. J. Mol. Sci. 2022, 23, 9237. https://doi.org/10.3390/ijms23169237
Gagliardi S, Truffi M, Tinelli V, Garofalo M, Pandini C, Cotta Ramusino M, Perini G, Costa A, Negri S, Mazzucchelli S, et al. Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients. International Journal of Molecular Sciences. 2022; 23(16):9237. https://doi.org/10.3390/ijms23169237
Chicago/Turabian StyleGagliardi, Stella, Marta Truffi, Veronica Tinelli, Maria Garofalo, Cecilia Pandini, Matteo Cotta Ramusino, Giulia Perini, Alfredo Costa, Sara Negri, Serena Mazzucchelli, and et al. 2022. "Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients" International Journal of Molecular Sciences 23, no. 16: 9237. https://doi.org/10.3390/ijms23169237