Poly(rC)-binding protein 1 alleviates neurotoxicity in 6-OHDA-induced SH-SY5Y cells and modulates glial cells in neuroinflammation.

BACKGROUND: Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons and neuroinflammation. Previous research has identified the involvement of Poly (rC)-binding protein 1 (PCBP1) in certain degenerative diseases; however, its specific mechanisms in PD remain incompletely understood. METHODS: In this study, 6-OHDA-induced neurotoxicity in the cell lines SH-SY5Y, BV-2 and HA, was used to evaluate the protective effects of PCBP1. We assessed alterations in BDNF levels in SY5Y cells, changes in GDNF expression in glial cells, as well as variations in HSP70 and NF-κB activation. Additionally, glial cells were used as the in vitro model for neuroinflammation mechanisms. RESULTS: The results indicate that the overexpression of PCBP1 significantly enhances cell growth compared to the control plasmid pEGFP/N1 group. Overexpression of PCBP1 leads to a substantial reduction in early apoptosis rates in SH-SY5Y, HA, and BV-2 cells, with statistically significant differences (p < 0.05). Furthermore, the overexpression of PCBP1 in cells results in a marked increase in the expression of HSP70, GDNF, and BDNF, while reducing NF-κB expression. Additionally, in SH-SY5Y, HA, and BV-2 cells overexpressing PCBP1, there is a decrease in the inflammatory factor IL-6 compared to the control plasmid pEGFP/N1 group, while BV-2 cells exhibit a significant increase in the anti-inflammatory factor IL-10. CONCLUSION: Our findings suggest that PCBP1 plays a substantial role in promoting cell growth and modulating the balance of neuroprotective and inflammatory factors. These results offer valuable insights into the potential therapeutic utility of PCBP1 in mitigating neuroinflammation and enhancing neuronal survival in PD.

Investigating the neuroprotective potential of rAAV2-PCBP1-EGFP gene therapy against a 6-OHDA-induced model of Parkinson's disease.

OBJECTIVES: Previous studies have suggested a potential link between poly(rC)-binding protein 1 (PCBP1) and neurodegenerative diseases, including Parkinson's disease (PD). However, the precise role of PCBP1 in the pathogenesis of PD remains unclear. Therefore, the main objective of this study was to investigate the neuroprotective effects of PCBP1 in a PD model. METHODS: To evaluate the neuroprotective potential of PCBP1, we conducted cell count assays and observed the expression of heat shock protein 70 (HSP70) in SH-SY5Y cells exposed to 6-OHDA-induced neurotoxicity. Additionally, we utilized recombinant adeno-associated virus (rAAV2) vectors encoding PCBP1 or EGFP, which were injected into the rat striatum. After 2 weeks of vector or saline injection, 6-OHDA was administered to the rat striatum. Behavioral assessments using the open field test (OFT) were performed weekly for 7 weeks. At the seventh week after 6-OHDA injection, immunohistochemistry and protein expression analyses were conducted in the three groups. RESULTS: The results indicated that PCBP1 treatment significantly reduced the proliferation of 6-OHDA-induced SH-SY5Y cells. Additionally, in surviving cells, overexpression of PCBP1 enhanced the expression of HSP70. Similarly, rAAV2 vectors effectively delivered PCBP1 into the brain, resulting in sustained expression of rAAV2-PCBP1-EGFP. In the OFT, PCBP1 exhibited significant improvements in behavioral abnormalities and reduced anxiety in the PD model rats (p < .01). Moreover, PCBP1 effectively prevented the decrease of tyrosine hydroxylase and HSP70 expression in the lesioned side induced by 6-OHDA (p < .01). Consistent with expectations, PCBP1 efficiently protected against cell death caused by 6-OHDA (p < .01). CONCLUSIONS: In conclusion, our findings provide compelling evidence for the beneficial effects of PCBP1 in the PD model, suggesting that PCBP1 could be a potential therapeutic target for PD.

Effects of Femtosecond Laser-Assisted Cataract Surgery on Macular and Choroidal Thickness in Diabetic Patients.

INTRODUCTION: This study aimed to compare the short-term changes in retinal and choroid thickness in diabetic patients after femtosecond laser-assisted cataract surgery (FLACS) and phacoemulsification (PE) surgery. METHODS: A total of 47 eyes in the PE group and 44 eyes in the FLACS group were included. All patients underwent measurement of central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) before and after surgery using optical coherence tomography (OCT). RESULTS: The effective phaco time (EPT) in the FLACS group was significantly reduced. The BCVA differed significantly between the two groups at 1 week and 1 month after surgery. The CMT in both groups increased at 1 week after the operation. It did not return to the preoperative level until month 12 in the PE group. In the FLACS group, the CMT began to decrease at month 3 and recovered to the preoperative level at month 12. The SFCT of the two groups increased at week 1; it began to decrease at month 6 in the PE group but did not recover to the preoperative level until month 12. The SFCT in the FLACS group recovered to preoperative levels at month 6. In the PE group, baseline CMT values predicted CMT change at week 1 and months 1, 3 and 12 after surgery. In the FLACS group, baseline CMT predicted CMT changes at week 1, month 1 and month 3. In the FLACS group, EPT predicted SFCT change at month 3. CONCLUSION: FLACS is safe and effective in patients with no fundus change or mild diabetic retinopathy. It has advantages in effectively reducing EPT, achieving good vision earlier and promoting faster recovery of the retinal and choroidal thickness. Preoperative CMT is a significant predictor of CMT changes in the early period after FLACS.

Clinical Evaluation of Tumor Markers for Diagnosis in Patients with Non-small Cell Lung Cancer in China.

BACKGROUND: To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of non- small cell lung cancer (NSCLC). MATERIALS AND METHODS: Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. RESULTS: Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (P<0.05). The sensitivity of CEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA+CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (P<0.05) and elevation of serum CEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (P<0.05). CONCLUSIONS: Single measurement of CEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA+CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.