Parkinson’s disease (PD) is
a devastating disease of the
central nervous system that occurs mainly in the elderly age group,
affecting their quality of life. The PD pathogenesis is not yet fully
understood and lacks the disease-modifying treatment strategies. Sanghuangprous vaninii (S. vaninii) is a perennial fungus with a plethora of pharmacological activities
including anti-cancer and antioxidant activity and so on. However,
no study till date has reported its neuroprotective effect against
symptoms that are similar to PD in pre-clinical investigation. In
the current study, we investigated anti-PD-like effects of S. vaninii mycelium extracts (SvMEs) on MPTP-induced
PD in zebrafish. We observed that the loss of dopaminergic neurons
and neurovascular reduction were reversed by using SvMEs in the zebrafish
brain in a concentration-independent manner. Moreover, it also relieved
locomotor impairments in MPTP-induced PD zebrafish. In addition, SvMEs
exerted significant antioxidant activity in vitro, which was also demonstrated in vivo on ktr4:NTR-hKikGR zebrafish. Upon investigating the underlying
mechanism, we found that SvMEs may alleviate oxidant stress and accelerate
α-synuclein degradation and then alleviate PD-like symptoms.
Antioxidant-related genes (sod1, gss, gpx4a, gclm, and cat) implied that the SvMEs exhibited anti-PD activity due to the antioxidation
mechanism. Finally, upon analysis of chemical composition of SvMEs
by liquid chromatography–mass spectrometry, we identified 10
compounds that are plausibly responsible for the anti-PD-like effect
of SvMEs. On the limiting part, the finding of the study would have
been more robust had we investigated the protein expression of genes
related to PD and oxidative stress and compared the effects of SvMEs
with any standard anti-PD therapy. Despite this, our results indicated
that SvMEs possess anti-PD effects, indicating SvMEs as a potential
candidate that is worth exploring further in this avenue.
Paired box 6 (PAX6) is a transcription factor that has oncogenic features. In breast cancer, PAX6 facilitates tumor progression; however, the underlying mechanism is largely unknown. The majority of breast cancer-related mortalities are associated with metastasis of cancer cells. Therefore, the present study aimed to investigate the role of PAX6 in breast tumor metastasis. PAX6 was stably overexpressed in breast cancer cells to perform tumor migration and metastasis assays in vitro and in vivo. In addition, the expression of PAX6 and transforming growth factor β (TGF-β)-SMAD signaling associated proteins on human breast cancer tissue array, as well as key factors involved in epithelial-mesenchymal transition (EMT) were assayed to explore the mechanism underlying metastasis of breast cancer cells. The expression levels of PAX6 were demonstrated to be increased in human breast cancer tissues and associated with poor clinical outcomes. Overexpression of PAX6 markedly promoted metastasis. Further investigation revealed that PAX6 overexpression increased TGF-β-SMAD signaling pathway and induced EMT. These results suggested that highly expressed PAX6 led to EMT through TGF-β-SMAD signaling pathway, thereby promoting cell metastasis and ultimately affecting survival in patients with breast cancer. Taken together, findings indicated that PAX6 may serve as a therapeutic target for the clinical treatment of breast cancer and the underlying mechanism could be used to overcome metastasis of cancer cells.
AimsThis study aims to reveal a promising biomarker for Parkinson's disease (PD) based on research with reverse phase protein array (RPPA) technology for the first time and in vivo verification, which gains time for early intervention in PD, thus increasing the effectiveness of treatment and reducing disease morbidity.Methods and ResultsWe employed RPPA technology which can assess both total and post‐translationally modified proteins to identify biomarker candidates of PD in a cellular PD model. As a result, the phosphorylation (pY‐1248) of the epidermal growth factor receptor (EGFR) ErbB2 is a promising biomarker candidate for PD. In addition, lapatinib, an ErbB2 tyrosine kinase inhibitor, was used to verify this PD biomarker candidate in vivo. We found that lapatinib‐attenuated dopaminergic neuron loss and PD‐like behavior in the zebrafish PD model. Accordingly, the expression of ErbB2pY‐1248 significantly increased in the MPTP‐induced mouse PD model. Our results suggest that ErbB2pY‐1248 is a predictive biomarker for PD.ConclusionsIn this study, we found that ErbB2pY‐1248 is a predictive biomarker of PD by using RPPA technology and in vivo verification. It offers a new perspective on PD diagnosing and treatment, which will be essential in identifying individuals at risk of PD. In addition, this study provides new ideas for digging into biomarkers of other neurodegenerative diseases.
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