We aimed to explore the mechanism of pramipexole (PPX) actions in the treatment of Parkinson’s disease (PD). Genes related to PD and PPX were screened through bioinformatics retrieval. The PD model was constructed by applying 1-methyl-4-phenylpyridinium (MMP+). The RNA expression levels of circSNCA, SNCA, apoptosis-related genes (BCL2, CASP3, BAX, PTEN and P53) and miR-7 were detected by qRT-PCR. Protein expression was determined by western blot. The interactions between circSNCA-miR-7-SNCA were verified by dual luciferase assay and immunofluorescence localization. Cell viability was determined by MTT assay. SNCA and circSNCA expression levels in PD were downregulated after PPX treatment, consistent with the levels of pro-apoptotic genes. CircSNCA increased SNCA expression by downregulating miR-7 in PD as a competitive endogenous RNA (ceRNA). Lower circSNCA expression was associated with the reduced expression of pro-apoptotic (CASP3, BAX, PTEN and P53) proteins. CircSNCA downregulation could decrease apoptosis and induce autophagy in PD. In conclusion, the downregulation of circSNCA by PPX treatment reduced cell apoptosis and promoted cell autophagy in PD via a mechanism that served as a miR-7 sponge to upregulate SNCA.

Glioma is the most common primary brain tumor among adults. Temozolomide (TMZ) is widely used as the first‑line postsurgical drug for malignant glioma. However, the therapeutic efficacy of TMZ remains ineffective as inherited or acquired drug resistance is frequently observed. Estrogen receptor β (ERβ) has emerged as a tumor suppressor and a key regulator of signal transduction in glioma cells. However, little is known about the role of ERβ in regulating the chemotherapeutic response to TMZ. In the current study, the TMZ‑resistant U138 glioma cells were treated with the novel ERβ agonist liquiritigenin (Liq). It was observed that Liq significantly enhanced ERβ expression and sensitized glioma cells to TMZ‑induced proliferation inhibition. As a potential mechanism, it was noted that Liq treatment significantly inhibited the activity of the PI3K/AKT/mTOR pathway, which played a protective role against the TMZ‑induced cytotoxicity. In addition, it was demonstrated that ERβ knockdown or activation of the phosphatidylinositol‑4,5‑bisphosphate 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by insulin‑like growth factor 1 both eradicated the function of Liq. These results suggest that Liq treatment enhances glioma cell susceptibility to TMZ by inhibiting the PI3K/AKT/mTOR pathway. As hyperactivation of the PI3K/AKT/mTOR pathway is frequently observed in gliomas, the combined use of ERβ agonists may become a feasible therapy option to overcome chemoresistance to TMZ.

Background/Aims: We aimed to explore the protective role of curcumin (Cur) in a cell model of Parkinson’s disease (PD) and its underlying mechanism. Methods: In this study, genes concerned with PD-related keywords were screened within DiGSeE database. The association network between Cur and selected genes was downloaded from STITCH, with the interactions analyzed by STRING. We built a mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP⁺)-induced SH-SY5Y cell model of PD. Cell morphology was observed under an electron microscope. MTT assay was applied to detect cell proliferation rate. Western blot assay was conducted to determine the level of apoptotic markers, including cleaved caspase 3, Bcl-2-associated X protein (Bax) and B-cell lymphoma-extra-large (Bcl-xl). Tyrosine hydroxylase (TH), dopamine transporter (DAT) protein levels and dopamine (DA) concentration were identified as dopaminergic neuron markers and measured by western blotting or Enzyme-linked immunosorbent assay (ELISA). Results: Cur rescued the toxicity effects of MPP⁺ on SH-SY5Y cells, by controlling morphological change, promoting cell proliferation and inhibiting apoptosis. Of all PD-related genes, HSP90 played an important role in Cur-gene network. HSP90 protein level was elevated by MPP⁺, whereas Cur could reverse this effect. Silencing of HSP90 significantly attenuated the curative effect introduced by Cur, while HSP90 overexpression enhanced the impact of Cur on PD. Conclusion: Cur can effectively inhibit the toxic effect of MPP⁺ on SH-SY5Y cells and significantly reduce the adverse effects of MPP⁺ on dopaminergic neurons via up-regulation of HSP90.

Objective We focused on the effects of PTGS2/NF‐κB signaling pathway on the radiation resistance of glioma in the study. Methods We downloaded the microarray data from the Gene Expression Omnibus (GEO) database. We verified transfection successfully through QRT‐PCR analysis. Immunofluorescence was used to detect γH2AX content under 2 Gy radiation. The survival rates of cells under 2 Gy irradiation were tested by clonogenic survival assay. Flow cytometry was used to detect cell cycle. Western blot was applied to detect the expression of NF‐κB pathway‐related proteins. We also used MTT assay to detect the proliferation of cells. Results In this research, we discovered that the expression of the PTGS2 was upregulated in radiation‐resistant glioma cells. The radio‐tolerance rate of U87 cells was obviously elevated after the overexpression of PTGS2. The radioresistance of U87R cells was significantly reduced after the knockdown of PTGS2. After radiotherapy, the number of cells arrested in G2/M phase decreased after PTGS2 overexpression in U87cells but increased in PTGS2 knockdown in U87R cells. The survival rate of U87 and U87R cells under radiation decreased significantly after the addition of NF‐κB inhibitor. The proliferation of U87 cells was suppressed by radiation and the addition of Bay 11. In addition, PTGS2 activated NF‐κB signaling pathway and prevented DNA damage after radiotherapy. Lastly, PTGS2 was proved to facilitate tumor cell proliferation and improve the radio‐tolerance. Conclusion PTGS2/NF‐κB signaling pathway was involved in radio‐tolerance of glioma cells, which provided a new insight into glioma therapy.

INTRODUCTION Glioma, a malignant brain tumor that arises from the brain's supportive tissue, is known as glial tumor [1]. The tumor is predominantly made up of abnormal astrocytic cells, but also contains a mix of different cell types (including blood vessels) and areas of dead cells. Glioma is aggressive that invades into regions of brain that are nearby. Exceedingly rare is for glioma to spread outside of the brain [2]. The molecular mechanism involved in the proliferation and invasion of glioma remains poorly understood in spite of an increasingly thorough depth of knowledge were acknowledged [3, 4]. Recent advances in whole-genome sequencing technology have led to the discovery of a new type of regulatory gene, that is long non-coding RNAs (hereafter referred to as lncRNAs), which are more than www.aging-us.com

The basic helix-loop-helix (bHLH) superfamily of transcription factors have been implicated in a wide range of cellular functions such as proliferation, differentiation, tumorigenesis, and circadian rhythms. In a previous siRNA-based screen, bHLH family member e41 (BHLHE41) had been identified as a putative regulator of neuronal differentiation; however, its function remains largely elusive. To this end, using the CRISPR-Cas9 system, we established an isogenic Neuro2a (N2a) cell line with biallelic targeting of Bhlhe41 gene (Bhlhe41). In undifferentiated N2a cells, complete knockout of Bhlhe41 resulted in marked proliferation inhibition, together with accumulation of apoptotic cells. Furthermore, retinoic acid (RA)-induced neurite outgrowth and expression of neuronal markers are significantly weakened in Bhlhe41 cells. We also showed that the activity of ERK1/2 signaling, a key regulator of neuronal differentiation, is likewise impaired in knockout cells. Together, these results suggest that Bhlhe41 plays critical roles in regulating cell death and neurite outgrowth in N2a cells.

Periodic paralysis (PP) is an uncommon inherited disorder causing recurrent episodes of muscle weakness, with an incidence of 0.001%. Normokalemic periodic paralysis (NormoKPP) as the rarest subtype of PP contains both familial and sporadic. Familial NormoKPP caused by the p.M1592V mutation of the skeletal muscle sodium channel alpha subunit (SCN4A) gene is rarely reported. Only three pedigrees of NormoKPP related to mutations in the SCN4A p.M1592V have been previously reported. We herein presented a family case of NormoKPP associated with the SCN4A p.M1592V mutation, in which respiratory muscle paralysis occurred in the proband while not in his children. Moreover, we conducted a thorough literature review. To our knowledge, this is the first report of respiratory muscle paralysis as a symptom of NormoKPP associated with mutation in the SCN4A p.M1592V.

In this study, 17 Y chromosomal short tandem repeats (Y-STRs) were analyzed in 302 male individuals from the Chinese Han and Korean populations of Jilin Province. The haplotype diversities of two populations reached 0.99969 and 0.99874, respectively. The Jilin Han and Korean populations differed from each other significantly. The Jilin Han population showed no significant difference from almost any other Han population, but it did show significant differences from most other Chinese ethnic populations. The haplotype frequencies in the Jilin Korean population studied here showed significant differences from all reference populations in earlier reports. These data provide a reference for the Y-STR database in Jilin Province, and they may be valuable for population genetic analysis.