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.

Association of Homocysteine Levels With Medial Temporal Lobe Atrophy Among Carriers and Non-carriers of APOE ε4 in MCI Subjects.

Background: Different clinical subtypes of mild cognitive impairment (MCI) involve heterogeneous underlying etiologies. This study investigated the association between demographics, neuropsychological performance, apolipoprotein E (APOE) genotype and magnetic resonance imaging (MRI) measures in patients with MCI (amnestic [aMCI] and non-amnestic [naMCI]). Methods: This case-control study included 130 aMCI patients, 58 naMCI patients, and 1,106 healthy controls (HCs). APOE genotypes, medial temporal lobe atrophy (MTA), neurological evaluation results, and white matter hyperintensities (WMH) were investigated. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma hyperhomocysteinemia (Hcy) was assessed by a high-performance liquid chromatography-fluorescence method. Results: Serum folate levels were significantly lower, but plasma Hcy levels were higher, in patients with aMCI and naMCI than in healthy controls. There were significantly higher MTA scores in the aMCI group than the healthy control group. Multiple linear regression showed that serum Hcy and folate concentrations were positively associated with MTA (p < 0.05), while APOE4 showed a significant negative association with MTA in the aMCI group (p < 0.01). In addition, moderate/severe WMH showed a significant negative association with MTA in the naMCI and HC groups (p < 0.01). Conclusion: The combined presence of APOE4 and Hcy is associated with aMCI in elderly individuals, while moderate/severe WMH is related to naMCI, which suggests etiological differences across MCI subtypes.

The Association Between the Prevalence, Medication Adherence and Control of Hypertension and the Prevalence of Mild Cognitive Impairment in Rural Northern China: A Cross-Sectional Study.

INTRODUCTION: High blood pressure is one of the main modifiable risk factors for dementia. However, it remains unclear whether lowering the blood pressure effectively prevents cognitive impairment. Our objective was to explore the association between the prevalence, medication adherence and control of hypertension and mild cognitive impairment (MCI) among elderly individuals in northern China. METHODS: A two-stage clustering sampling method was used, and 9036 participants aged ≥65 years were included in the analysis. The Mini-Mental State Examination and activities of daily living were used to assess participants' cognitive function. Demographic characteristics (gender, age, marital status, education level, occupation), history and duration of hypertension, use of antihypertensive medications (AHMs) and its control effect were obtained. RESULTS: The prevalence of MCI in all participants was 18.1%, and the prevalence of MCI was significantly higher in hypertensive subjects than in normotensive subjects (19.7% vs 16.2%, P < 0.01). Furthermore, in hypertensive patients, the prevalence of MCI was lower in those with good adherence (17.3%) than in those with poor adherence (23.7%, P < 0.01) and lower in those controlled (16.5%) than in those with uncontrolled adherence (20.8%, P < 0.01). In univariate analyses, being female gender, increased age, agriculture occupation, unmarried and widow, less than primary school and middle school were associated with MCI prevalence. The assessment of the hypertensive patients revealed the adjusted OR (95% CI) of having MCI in those with poor adherence to AHMs was 1.32 (1.14-1.54) compared with those having good adherence. CONCLUSION: There is an association between the prevalence of hypertension, adherence to AHMs and MCI, suggesting that hypertensives should be screened for MCI to provide improved diagnoses and optimal therapeutics for cognitive decline prevention, especially in poor AHM adherence.

Prevalence and risk factors of stroke in a rural area of northern China: a 10-year comparative study.

BACKGROUND AND AIMS: Stroke is currently the leading cause of death in China; however, the past decade has produced no new epidemiological studies of stroke. Therefore, the current study aimed to compare the prevalence and risk factors of stroke between 2010 and 2019. METHODS: A comparative study was used to analyze the prevalence of risk factors for stroke in a population aged 65 years or older between 2010 and 2019. Demographic characteristics, risk factors, medical history, and other clinical characteristics were collected for all participants via door-to-door interviews and inpatient hospital records. RESULTS: The standardized prevalence of stroke was 7.9% in 2010 and 14.2% in 2019 (p < 0.001). The prevalence of stroke was significantly higher in men than in women (p < 0.05) for all age groups. The risk factors of stroke were being male, hypertension, and diabetes mellitus in both 2010 and 2019. When comparing the risk factors between 2010 and 2019, these risk factors were statistically significantly more strongly associated with stroke in 2019 than in 2010. CONCLUSION: The current study suggests that the prevalence of stroke increased nearly by twofold in a population aged 65 years or older within the past 10 years. Hypertension, diabetes mellitus, and being male were the primary risk factors. In addition, these factors were more significantly associated with stroke in 2019 compared to 2010.

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.

Precision and accuracy of commercial assays for vancomycin therapeutic drug monitoring: evaluation based on external quality assessment scheme.

BACKGROUND: Vancomycin remains a mainstay of the treatment of Gram-positive bacterial infections. It is crucial to accurately determine vancomycin serum concentration for adequate dose adjustment. OBJECTIVES: To evaluate the precision and accuracy of commercial assay techniques for vancomycin concentration and to assess the comparability of vancomycin detection methods in Chinese laboratories. METHODS: Human serum samples spiked with known concentrations of vancomycin were provided to laboratories participating in the external quality assessment scheme (EQAS). Assay methods included chemiluminescence, enzyme immunoassay (EIA) and so on. The dispersion of the measurements was analysed and the robust coefficient of variation (rCV), relative percentage difference (RPD) and satisfactory rate for method groups were calculated. Moreover, performance of the Chinese laboratories was assessed. RESULTS: A total of 657 results from 75 laboratories were collected, including 84 samples from 10 Chinese laboratories. The median rCV, median RPD and satisfactory rates classified by methods ranged from 1.85% to 15.87%, -14.75% to 13.34% and 94.59% to 100.00%, respectively. Significant differences were seen in precision, between kinetic interaction of microparticles in solution (KIMS) and other methods, and in accuracy, between enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA) and other techniques. Vancomycin detection in China mainly depended on the chemiluminescence and EMIT methods, which tended to result in lower measurements. CONCLUSIONS: Although almost all assays in this study achieved an acceptable performance for vancomycin serum concentration monitoring, obvious inconsistencies between methods were still observed. Chinese laboratories were more likely to underestimate vancomycin concentrations. Thus, recognizing inconsistencies between methods and regular participation in vancomycin EQAS are essential.

The efficacy and safety of fingolimod in patients with relapsing multiple sclerosis: A meta-analysis.

AIMS: The aim of the present meta-analysis was to evaluate the efficacy and safety of fingolimod in patients with relapsing multiple sclerosis (RMS). METHODS: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for relevant studies. Two authors independently selected the studies, assessed the risk of bias, and extracted the data. The meta-analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration. RESULTS: Ten studies met the inclusion criteria. In patients with RMS, fingolimod demonstrated a significantly lower annualized relapse rate (0.5 mg/d: mean difference [95% confidence interval] = -0.22 [-0.29 to -0.14]; 1.25 mg/d: -0.26 [-0.36 to -0.16]; 5 mg/d: -0.41 [-0.72 to -0.10]) than placebo. Fingolimod also exhibited a favorable performance on other magnetic resonance imaging outcomes and improved the quality of life in patients. No significant difference was noted in the prevalence of adverse events between the fingolimod treatment group and the placebo/disease-modifying therapy groups. CONCLUSIONS: Fingolimod may offer benefits for RMS patients and presents an acceptable safety profile.

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.

Uncinoside A and B, two new antiviral chromone glycosides from Selaginella uncinata.

Five compounds have been isolated from the dried whole plants of Selaginella uncinata, two of them were new chromone glycosides, 5-hydroxy-2,6,8-trimethylchromone 7-O-beta-D-glucopyranoside (uncinoside A) and 5-acetoxyl-2,6,8-trimethylchromone 7-O-beta-D-glucopyranoside (uncinoside B). Their structures were elucidated by spectroscopic methods including one- and two-dimensional NMR techniques. The other three compounds were identified as 8-methyl eugenitol, amentoflavone and hinokiflavone. Uncinoside A and B showed potent antiviral activities against respiratory syncytial virus (RSV) with IC(50) value of 6.9 and 1.3 microg/ml, moderate antiviral activities against parainfluenza type 3 virus (PIV 3) with IC(50) value of 13.8 and 20.8 microg/ml, respectively.