scholarly journals Preventive Activity of the Extract of the Darkling Beetle Ulomoides Dermestoides in the Diet of C57Bl/6JSTO Mice in a Neurotoxic Model of Parkinson's Disease

2021 ◽  
Author(s):  
Vladimir M. Kovalzon ◽  
Alexander V. Ambaryan ◽  
Alexander V. Revishchin ◽  
Ekaterina Y. Rybalkina ◽  
Alexander I. Bastrakov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Biologically Active ◽  
Human Neuroblastoma ◽  
Delayed Effects ◽  
Darkling Beetle ◽  
Preventive Activity ◽  
And Control

The effect of aqueous extracts of the biomass of the adult beetle Ulomoides dermestoides on the delayed effects of defoliant paraquat causing parkinsonism in experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrain of experimental and control mice were studied by immunohistochemistry. In the model in vitro system with SH-SY5Y–human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and in the presence of the neurotoxin MPP+. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used.

scholarly journals Preventive Activity of the Extract of the Darkling Beetle Ulomoides Dermestoides in the Diet of C57Bl/6JSTO Mice in a Neurotoxic Model of Parkinson's Disease

2021 ◽  
Author(s):  
Vladimir M. Kovalzon ◽  
Alexander V. Ambaryan ◽  
Alexander V. Revishchin ◽  
Galina V. Pavlova ◽  
Ekaterina Y. Rybalkina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Biologically Active ◽  
Human Neuroblastoma ◽  
Delayed Effects ◽  
Darkling Beetle ◽  
Preventive Activity ◽  
And Control

The effect of aqueous extracts of the biomass of the adult Ulomoides dermestoides beetle on the delayed effects of the defoliant paraquat causing parkinsonism in experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP+. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.

scholarly journals Biological Activity of the Tenebrionidae Beetle Antioxidant Complex in a Murine Neurotoxic Model of Parkinson's Disease

2021 ◽  
Author(s):  
Vladimir Kovalzon ◽  
Aleksandr Ambaryan ◽  
Aleksandr Revishchin ◽  
Galina Pavlova ◽  
Ekaterina Rybalkina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biological Activity ◽  
Early Stage ◽  
Biologically Active ◽  
Human Neuroblastoma ◽  
Protein Nature ◽  
And Control

Abstract We have previously shown that the aqueous extract of the Ulomoides dermestoides darking beetle (the Tenebrionidae family) biomass contains a powerful complex of antioxidant substances of protein and non-protein nature. Considering the crucial role of ROS in the development of neurodegeneration, we set out to test the biological activity of this extract in a mouse neurotoxic model of Parkinson's disease. The beetle extracts were administrated continuously with food and their effects on parkinsonism caused by twice injected defoliant paraquat to experimental mice was evaluated. The motor activity of the animals was analyzed in behavioral tests using a rotarod and a vertical pole. The number of tyrosine hydroxylase-immunopositive neurons in the ventral part of the substantia nigra of the midbrains of experimental and control mice was studied by immunohistochemistry. In the model in vitro system with SH-SY5Y human neuroblastoma, the effect of the extracts on cell proliferation was examined in the absence and presence of the neurotoxin MPP+. The isolation of biologically active substances from raw biomass using cavitation effects made it possible to obtain extracts with protective properties in the model of an early stage of Parkinson's disease used in this study.

scholarly journals Holistic Metabolomic Laboratory-Developed Test (LDT): Development and Use for the Diagnosis of Early-Stage Parkinson’s Disease

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 14
Author(s):  
Petr G. Lokhov ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Oxana P. Trifonova ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Molecular Weight ◽  
Parkinson's Disease ◽  
High Resolution Mass Spectrometry ◽  
Early Stage ◽  
Disease Diagnosis ◽  
The Body ◽  
Low Molecular Weight ◽  
Low Molecular Weight Compounds

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is developed and used within a single laboratory. The holistic metabolomic LDT integrating the currently available data on human metabolic pathways, changes in the concentrations of low-molecular-weight compounds in the human blood during diseases and other conditions, and their prevalent location in the body was developed. That is, the LDT uses all of the accumulated metabolic data relevant for disease diagnosis and high-resolution mass spectrometry with data processing by in-house software. In this study, the LDT was applied to diagnose early-stage Parkinson’s disease (PD), which currently lacks available laboratory tests. The use of the LDT for blood plasma samples confirmed its ability for such diagnostics with 73% accuracy. The diagnosis was based on relevant data, such as the detection of overrepresented metabolite sets associated with PD and other neurodegenerative diseases. Additionally, the ability of the LDT to detect normal composition of low-molecular-weight compounds in blood was demonstrated, thus providing a definition of healthy at the molecular level. This LDT approach as a screening tool can be used for the further widespread testing for other diseases, since ‘omics’ tests, to which the metabolomic LDT belongs, cover a variety of them.

Retinal Morphological Changes during the Two Years of Follow-Up in Parkinson's Disease

2020 ◽  
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryurek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
Morphological Changes ◽  
Fiber Layer ◽  
Significant Difference ◽  
Yahr Scale ◽  
And Control

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

scholarly journals Diagnosis of Parkinson’s Disease by A Metabolomics-Based Laboratory-Developed Test (LDT)

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 332 ◽  
Author(s):  
Petr G. Lokhov ◽  
Oxana P. Trifonova ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Mass Spectrometry Analysis ◽  
Great Effort ◽  
Spectrometry Analysis ◽  
Yahr Scale ◽  
In Vitro Diagnostic ◽  
Stage 1

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used in the same laboratory (i.e., an in-house test). In this study, a metabolomics-based LDT was developed. This test involves a blood plasma preparation, direct-infusion mass spectrometry analysis with a high-resolution mass spectrometer, alignment and normalization of mass peaks using original algorithms, metabolite annotation by a biochemical context-driven algorithm, detection of overrepresented metabolic pathways and results in a visualization in the form of a pathway names cloud. The LDT was applied to detect early stage Parkinson’s disease (PD)—the diagnosis of which currently requires great effort due to the lack of available laboratory tests. In a case–control study (n = 56), the LDT revealed a statistically sound pattern in the PD-relevant pathways. Usage of the LDT for individuals confirmed its ability to reveal this pattern and thus diagnose PD at the early-stage (1–2.5 stages, according to Hoehn and Yahr scale). The detection of this pattern by LDT could diagnose PD with a specificity of 64%, sensitivity of 86% and an accuracy of 75%. Thus, this LDT can be used for further widespread testing.

scholarly journals Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an In Vitro Model of Parkinson’s Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 326 ◽  
Author(s):  
Nadia Ferlazzo ◽  
Santa Cirmi ◽  
Alessandro Maugeri ◽  
Caterina Russo ◽  
Giovanni Enrico Lombardo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nuclear Translocation ◽  
Neuroprotective Effect ◽  
Neuroblastoma Cells ◽  
Specific Cell ◽  
Protective Effects ◽  
Human Neuroblastoma

Much evidence suggests that both oxidative stress and apoptosis play a key role in the pathogenesis of Parkinson’s disease (PD). The present study aims to evaluate the protective effect of bergamot juice (BJ) against 6-hydroxydopamine (6-OHDA)- or H2O2-induced cell death. Treatment of differentiated SH-SY5Y human neuroblastoma cells with 6-OHDA or H2O2 resulted in cell death that was significantly reduced by the pre-treatment with BJ. The protective effects of BJ seem to correlate with the reduction of intracellular reactive oxygen species and nitric oxide generation caused by 6-OHDA or H2O2. BJ also attenuated mitochondrial dysfunction, caspase-3 activation, imbalance of pro- and anti-apoptotic proteins, MAPKs activation and reduced NF-ĸB nuclear translocation evoked by neurotoxic agents. Additionally, BJ exhibited excellent antioxidant capability in cell-free assays. Collectively, our results suggest that BJ exerts neuroprotective effect through the interplay with specific cell targets and its antioxidant activity, making it worthy of consideration for the management of neurodegenerative diseases.

scholarly journals Neuroprotection of Granulocyte Colony-Stimulating Factor for Early Stage Parkinson's Disease

2017 ◽  
Vol 26 (3) ◽  
pp. 409-416 ◽  
Author(s):  
Sheng-Tzung Tsai ◽  
Sung-Chao Chu ◽  
Shu-Hsin Liu ◽  
Cheng-Yoong Pang ◽  
Ting-Wen Hou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Early Stage ◽  
In Vivo Studies ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Elevated Liver Enzymes ◽  
Stimulating Factor

Parkinson's disease (PD) is a slowly progressive neurodegenerative disease. Both medical and surgical choices provide symptomatic treatment. Granulocyte colony-stimulating factor (G-CSF), a conventional treatment for hematological diseases, has demonstrated its effectiveness in acute and chronic neurological diseases through its anti-inflammatory and antiapoptosis mechanisms. Based on previous in vitro and in vivo studies, we administered a lower dose (3.3 μg/kg) G-CSF injection for 5 days and six courses for 1 year in early-stage PD patients as a phase I trial. The four PD patient's mean unified PD rating scale motor scores in medication off status remained stable from 23 before the first G-CSF injection to 22 during the 2-year follow-up. 3,4-Dihydroxy-6-18F-fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) studies also revealed an annual 3.5% decrease in radiotracer uptake over the caudate nucleus and 7% in the putamen, both slower than those of previous reports of PD. Adverse effects included transient muscular–skeletal pain, nausea, vomiting, and elevated liver enzymes. Based on this preliminary report, G-CSF seems to alleviate disease deterioration for early stage PD patients. The effectiveness of G-CSF was possibly due to its amelioration of progressive dopaminergic neuron degeneration.

scholarly journals A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity

2017 ◽  
Vol 114 (6) ◽  
pp. E1009-E1017 ◽  
Author(s):  
Michele Perni ◽  
Céline Galvagnion ◽  
Alexander Maltsev ◽  
Georg Meisl ◽  
Martin B. D. Müller ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Natural Product ◽  
Self Assembly ◽  
Lipid Membranes ◽  
Neuroblastoma Cells ◽  
Lipid Vesicles ◽  
Human Neuroblastoma

The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson’s disease and related conditions.

scholarly journals Neuroinductive properties of mGDNF depend on the producer, E. Coli or human cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258289
Author(s):  
Dzhirgala V. Shamadykova ◽  
Dmitry Y. Panteleev ◽  
Nadezhda N. Kust ◽  
Ekaterina A. Savchenko ◽  
Ekaterina Y. Rybalkina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ganglion Cells ◽  
Neuroblastoma Cells ◽  
Human Cells ◽  
Hek293 Cells ◽  
Human Neuroblastoma ◽  
Mammalian Expression

The glial cell line‐derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenerative disorders, ischemic stroke, and cerebral or spinal cord damages. Unproductive clinical trials of GDNF for Parkinson’s disease treatment have induced to study this failure. A reason could be due to irrelevant producer cells that cannot perform the required post-translational modifications. The biological activity of recombinant mGDNF produced by E. coli have been compared with mGDNF produced by human cells HEK293. mGDNF variants were tested with PC12 cells, rat embryonic spinal ganglion cells, and SH-SY5Y human neuroblastoma cells in vitro as well as with a mouse model of the Parkinson’s disease in vivo. Both in vitro and in vivo the best neuro-inductive ability belongs to mGDNF produced by HEK293 cells. Keywords: GDNF, neural differentiation, bacterial and mammalian expression systems, cell cultures, model of Parkinson’s disease.

scholarly journals Biologically Active Echinulin-Related Indolediketopiperazines from the Marine Sediment-Derived Fungus Aspergillus niveoglaucus

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 61 ◽  
Author(s):  
Olga F. Smetanina ◽  
Anton N. Yurchenko ◽  
Elena V. Girich (Ivanets) ◽  
Phan Thi Hoai Trinh ◽  
Alexander S. Antonov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
In Vitro Models ◽  
Biologically Active ◽  
Neuroprotective Activity ◽  
Chiral Hplc ◽  
Cytoprotective Activity ◽  
First Time

Seven known echinulin-related indolediketopiperazine alkaloids (1–7) were isolated from the Vietnamese sediment-derived fungus Aspergillus niveoglaucus. Using chiral HPLC, the enantiomers of cryptoechinuline B (1) were isolated as individual compounds for the first time. (+)-Cryptoechinuline B (1a) exhibited neuroprotective activity in 6-OHDA-, paraquat-, and rotenone-induced in vitro models of Parkinson’s disease. (−)-Cryptoechinuline B (1b) and neoechinulin C (5) protected the neuronal cells against paraquat-induced damage in a Parkinson’s disease model. Neoechinulin B (4) exhibited cytoprotective activity in a rotenone-induced model, and neoechinulin (7) showed activity in the 6-OHDA-induced model.

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