Parkinson’s disease (PD) is diagnosed when motor symptoms emerges, which almost 70% of dopamine neurons are lost. Therefore, early diagnosis of PD is crucial to prevent the progress of disease. Blood-based biomarkers, which are minimally invasive, potentially used for diagnosis of PD, including miRNAs. The aim of this study was to assess whether SRRM2 and miR-27a/b-3p could act as early diagnostic biomarkers for PD. Total RNAs from PBMCs of 30 PD’s patients and 14 healthy age and gender matched subjects was extracted. The expression levels of respective genes were assessed. Data were presented applying a two-tailed unpaired t-test and one-way ANOVA. We observed significant down-regulation of SRRM2 (p = 0.0002) and miR-27a-3p (p = 0.0001), and up-regulation of miR-27b-3p (p = 0.02) in PBMCs of Parkinson's patients. Down-regulation of miR-27a-3p is associated with increasing disease severity, whereas the up-regulation of miR-27b-3p was observed mostly at HY-1 and disease duration between 3–5 years. There was a negative correlation between SRRM2 and miR-27b-3p expressions, and miR-27a-3p positively was correlated with miR-27b-3p. Based on functional enrichment analysis, SRRM2 and miR-27a/b-3p acted on common functional pathways. miR-27a/b-3p could potentially predict the progression and severity of PD. Although both miRs had no similarity on expression, a positive correlation between both miRs was identified, supporting their potential role as biomarkers in clinical PD stages. Of note that SRRM2 and miR-27a-3p were able to distinguish PD patients from healthy individuals. Functional analysis of the similarity between genes associated with SRRM2 and miR-27a/b-3p indicates common functional pathways and their dysfunction correlates with molecular etiopathology mechanisms of PD onset.

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For many years, high-affinity subunit of IL-2 receptor (CD25) has been considered as a promising therapeutic target for different pathologic conditions like allograft rejection, autoimmunity, and cancers. Although CD25 is transiently expressed by newly-activated T cells, it is the hallmark of regulatory T (Treg) cells which are the most important immunosuppressive elements in tumor microenvironment. Thus, Tregs can be considered as a potential target for chimeric antigen receptor (CAR)-based therapeutic approaches. On the other hand, due to some profound adverse effects pertaining to the use of CAR T cells, CAR NK cells have caught researchers’ attention as a safer choice. Based on these, the aim of this study was to design and develop a CAR NK cell against CD25 as the most prominent biomarker of Tregs with the prospect of overcoming immune escape mechanism in solid and liquid cancers. In the current study, an anti-CD25 CAR was designed and evaluated by comprehensive in silico analyses. Then, using lentiviral transduction system, NK-92 cell line was engineered to express this anti-CD25 CAR construct. In vitro functional analyses of anti-CD25 CAR for its reactivity against CD25 antigen as well as for cytotoxicity and cytokine production assays against CD25 bearing Jurkat cell line were done. In silico analyses demonstrated that the anti-CD25 CAR transcript and scFv protein structures were stable and had proper interaction with the target. Also, in vitro analyses showed that the anti-CD25 CAR-engineered NK-92 cells were able to specifically detect and lyse target cells with an appropriate cytokine production and cytotoxic activity. To conclude, the results showed that this novel CAR NK cell is functional and warrant further investigations.