Abstract. Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5x10 5 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.
This work aims to develop and optimize blended polylactide-co-glycolide (PLGA) and poly(ε-caprolactone, PCL)
loaded with Boswellia sacra oil (BO)
to improve BO’s physicochemical properties and anti-breast
cancer effects via enhancing apoptosis. In this context,
BO was extracted from B. sacra oleo
gum resins (BO) via hydrodistillation and chemically
characterized by evaluating its essential oil’s composition
using gas chromatography–mass spectrometry. Then, BO/PLGA–PCL
NPs were formulated using the emulsion (O/W) solvent evaporation technique
using a PLGA–PCL mixture at five different ratios (1:1, 2:1,
3:1, 1:2, and 1:3, respectively). The optimized NPs had a spherical
morphology with no agglomerations and the lowest hydrodynamic size
(230.3 ± 3.7 nm) and polydispersity index (0.13 ± 0.03)
and the highest ζ potential (−20.36 ± 4.89 mV),
as compared to the rest of the formulas. PLGA–PCL NPs could
entrap 80.59 ± 3.37% of the BO and exhibited a controlled, sustained
release of BO (83.74 ± 3.34%) over 72 h. Encapsulating BO in
the form of BO/PLGA–PCL NPs resulted in a lower IC50 value as assessed by the MTT assay. Furthermore and upon assessing
the apoptotic effect of both BO and BO/PLGA–PCL NPs, there
was an increase in the percentage of apoptotic and necrotic cell percentages
compared to the control and free BO. Encapsulation of BO in PLGA–PCL
NPs doubled the percentage of apoptotic and necrotic cells exerted
by free BO. These findings support the potential use of BO/PLGA–PCL
NPs in treating breast cancer.
Trichloroethylene (TCE) is one of the industrial toxic byproducts that now persist in the air, soil, and water. Several studies have already illustrated the toxic effect of high doses of TCE on the biological functions of several organs. This study aims to highlight the toxic impact of a low dose of TCE (1 μmol/L) on the development of rat neural stem cells (NSCs). The subventricular zones (SVZ) of rat pup's brains were collected and minced, and the harvested cells were cultured in the presence of neural growth factors B27/N2 to develop neurospheres. The cells were then exposed to a dose of 1 μmol/L TCE for 1 or 2 weeks. The outcomes indicated a remarkable inhibitory effect of TCE on the differentiation capacity of NSCs, which was confirmed by down-regulation of the astrocyte marker GFAP The inhibitory effect of TCE on the proliferation of NSCs was identified by the reductions in neurosphere diameter, Ki67 expression, and cell cycle arrest at the G1/S phase. Immunolabelling with annexin V indicated the proapoptotic effect of TCE exposure. PCR results revealed a TCE-mediated suppression of the expression of the antioxidant enzyme SOD1. This paper illustrates, for the first time, a detailed examination of the toxic effects of an environmentally low dose of TCE on NCSs at the transcriptional, translational, and functional levels.
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