Corneal nerve fibre loss as a marker to identify the impact of diabetes on Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) suffer from serious quality of life problems. Diabetes has been demonstrated as an independent risk element for PD, aggravating its severity and accelerating its progression. There are currently no suitable biomarkers to reveal the impact of diabetes on PD. The purpose of our research was to study the impact of diabetes on PD using corneal confocal microscopy (CCM), a non-invasive and objective test. METHODS: Fourteen PD patients with diabetes (PD-DM), 60 PD patients without diabetes (PD-NDM), and 30 healthy controls (HC) were included in the study. The clinical symptoms of patients with PD were assessed using the Unified Parkinson's Disease Rating Scale-3 (UPDRS-3) and the Parkinson's Disease Autonomic Symptom Prognosis Scale (SCOPA-AUT). Participants underwent CCM to quantify the corneal nerve fibres. RESULTS: Corneal nerve fibre density (CNFD) and corneal nerve fibre length (CNFL) in patients with PD were lower than HC. Furthermore, CNFD in PD-DM was lower than in PD-NDM (P < 0.01). We also assessed the relationship between CCM parameters and clinical scores. CNFL and Hamilton anxiety (HAMA) have a negative correlation (r = -0.261, P = 0.032), but this study did not observe a significant correlation between CCM parameters and SCOPA-AUT. Additionally, CNFD could distinguish PD-DM from PD-NDM, achieving an area under the curve of 75.06% (95% CI, 61.76%-88.36%). CONCLUSIONS: The CCM could be served as an objective and sensitive biomarker to investigate the impact of diabetes in PD.

Corneal confocal microscopy may help to distinguish Multiple System Atrophy from Parkinson's disease.

Multiple system atrophy (MSA) and Parkinson's disease (PD) have clinical overlapping symptoms, which makes differential diagnosis difficult. Our research aimed to distinguish MSA from PD using corneal confocal microscopy (CCM), a noninvasive and objective test. The study included 63 PD patients, 30 MSA patients, and 31 healthy controls (HC). When recruiting PD and MSA, questionnaires were conducted on motor and non-motor functions, such as autonomic and cognitive functions. Participants underwent CCM to quantify the corneal nerve fibers. Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) values in MSA are lower than PD (MSA vs. PD: CNFD, 20.68 ± 6.70 vs. 24.64 ± 6.43 no./mm2, p < 0.05; CNFL, 12.01 ± 3.25 vs. 14.17 ± 3.52 no./mm2, p < 0.05). In MSA + PD (combined), there is a negative correlation between CNFD and the Orthostatic Grading Scale (OGS) (r = -0.284, p = 0.007). Similarly, CNFD in the only MSA group was negatively correlated with the Unified Multiple System Atrophy Rating Scale I and II (r = -0.391, p = 0.044; r = -0.382, p = 0.049). CNFD and CNFL were inversely associated with MSA (CNFD: ß = -0.071; OR, 0.932; 95% CI, 0.872 ~ 0.996; p = 0.038; CNFL: ß = -0.135; OR, 0.874; 95% CI, 0.768-0.994; p = 0.040). Furthermore, we found the area under the receiver operating characteristic curve (ROC) of CNFL was the largest, 72.01%. The CCM could be an objective and sensitive biomarker to distinguish MSA from PD. It visually reflects a more severe degeneration in MSA compared to PD.

Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation.

Small cell lung cancer (SCLC) is a subtype of lung cancer with a very poor overall survival rate due to its extremely high proliferation and metastasis predilection. Shikonin is an active ingredient extracted from the roots of Lithospermum erythrorhizon, and exerts multiple anti-tumor functions in many cancers. In the present study, the role and underlying mechanism of shikonin in SCLC were investigated for the first time. We found that shikonin effectively suppressed cell proliferation, apoptosis, migration, invasion, and colony formation and slightly induced apoptosis in SCLC cells. Further experiment indicated the shikonin could also induced ferroptosis in SCLC cells. Shikonin treatment effectively suppressed the activation of ERK, the expression of ferroptosis inhibitor GPX4, and elevated the level of 4-HNE, a biomarker of ferroptosis. Both total ROS and lipid ROS were increased, while the GSH levels were decreased in SCLC cells after shikonin treatment. More importantly, our data identified that the function of shikonin was dependent on the up-regulation of ATF3 by performing rescue experiments using shRNA to silence the expression of ATF3, especially in the total and lipid ROS accumulaiton. Xenograft model was established using SBC-2 cells, and the results revealed that shikonin also significantly inhibited tumor growth by inducing ferroptosis. Finally, our data further confirmed that shikonin activated ATF3 transcription by impairing the recruitment of HDAC1 mediated by c-myc on the ATF3 promoter, and subsequently elevating of histone acetylation. Our data documented that shikonin suppressed SCLC by inducing ferroptosis in a ATF3-dependent manner. Shikonin upregulated the expression of ATF3 expression via promoting the histone acetylation by inhibiting c-myc-mediated HDAC1 binding on ATF3 promoter.

The relationship between serum neurofilament light chain and glial fibrillary acidic protein with the REM sleep behavior disorder subtype of Parkinson's disease.

Studies have shown that rapid eye movement (REM) sleep behavior disorder (RBD) is a subtype of Parkinson's disease (PD) characterized by severe cognitive impairment and rapid disease progression. However, reliable biological markers are lacking presently. Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) have been widely studied as biomarkers of cognition impairment. This study aimed to find biomarkers for the RBD subtype of PD by investigating the possible relationship between serum NFL, GFAP levels, and the RBD subtype. A total of 109 PD patients and 37 healthy controls (HCs) were included, and their clinical characteristics were evaluated. PD patients were divided into two groups based on whether they had probable RBD or not. Serum NFL and GFAP levels were measured using the ultrasensitive single molecule array (Simoa) platform. The obtained data were statistically analyzed using SPSS 25.0 (IBM, Chicago, IL, USA). NFL and GFAP in the PD-RBD group were elevated compared with the PD-nRBD and control groups. Moreover, serum NFL and GFAP levels positively correlated with RBD. The combination of NFL and GFAP showed good performance in identifying PD-RBD patients from PD-nRBD. After considering potential confounding factors such as age, and disease duration, serum NFL and GFAP emerged as independent risk factors for RBD. Serum NFL and GFAP were related to RBD in PD patients. Concludingly, serum NFL and GFAP might serve as promising biomarkers for the RBD subtype of PD.