Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease.

BACKGROUND: Cognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. OBJECTIVE: To investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. METHODS: Eighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. RESULTS: Compared with the control group, the macular GCIPL (t = -2.308, P = 0.023) was thinner and serum HMGB1 (z = -2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. CONCLUSION: The macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.

Clinical findings of hyperechoic substantia nigra in patients with Parkinson's disease.

This study aims to analyse hyperechoic substantia nigra (HSN) characteristics and the correlation of HSN with clinical features and blood biomarkers in patients with Parkinson's disease (PD). Transcranial sonography (TCS) evaluations of the substantia nigra (SN) were performed in 40 healthy controls and 71 patients with PD, including patients with SN hyperechogenicity (SN+) and those with normal SN echogenicity (SN-). Evaluation of motor and non-motor symptoms was assessed by a series of rating scales. The uricase method was used to determine serum uric acid (UA) levels, and enzyme-linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)-1ß levels. TCS showed 92.50% specificity and 61.97% sensitivity in differentiating PD patients from controls. The area of SN+ contralateral to the side of initial motor symptoms (SNcontra) was larger than that ipsilateral to the side of initial motor symptoms (SNipsi). The PDSN+ group had lower Argentine Hyposmia Rating Scale (AHRS) scores and UA levels than the PDSN- group. Binary logistic regression analysis revealed that AHRS scores and UA levels could be independent predictors for HSN. The larger SN echogenic area (SNL) sizes positively correlated with plasma IL-1ß levels in PD patients with SN+. The present study provides further evidence of the potential of SN echogenicity as an imaging biomarker for PD diagnosis. PD patients with HSN have more severe non-motor symptoms of hyposmia. HSN in PD patients is related to the mechanism of abnormal iron metabolism and microglial activation.

Increased plasma lipocalin-2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease.

Lipocalin-2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel-based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Diagnostic value of plasma SIRT1 levels and whole-brain gray matter volume in Parkinson's disease patients with cognitive impairment.

OBJECTIVE: This study was designed to investigate the diagnostic value of plasma SIRT1 levels and whole-brain gray matter (GM) volume in Parkinson's disease (PD) patients with cognitive impairment. METHODS: Automated enzymatic analysis was performed to measure plasma SIRT1 levels in 80 healthy controls and 77 PD patients. Motor symptoms and nonmotor symptoms in PD patients were assessed using the corresponding scales. A Siemens MAGNETOM Prisma 3 T MRI scanner was used to acquire images in 35 of 77 PD patients. RESULTS: Plasma SIRT1 levels in PD patients were lower than those in healthy controls. Plasma SIRT1 levels were negatively correlated with the age, Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores, anxiety, depression, excessive daytime sleepiness (EDS), quality of life, and especially cognitive impairment. Thus, it showed that plasma SIRT1 levels were relevant to visuospatial/executive function, memory, and language. Receiver-operating characteristic (ROC) analysis confirmed that plasma SIRT1 levels had good diagnostic accuracy for PD with anxiety and EDS. Furthermore, plasma SIRT1 levels had a significant positive correlation with GM volume in the whole brain, and ROC analysis confirmed that plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. CONCLUSIONS: This study showed that plasma SIRT1 levels were correlated with the nonmotor symptoms of anxiety, depression, EDS, and especially cognitive impairment as well as the total GM volume. Furthermore, the combination of plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment.

A case of adrenomyeloneuropathy caused by a novel point mutation in the ABCD1 gene and functional verification.

Adrenoleukodystrophy is a rare neurogenetic disease, and adrenomyeloneuropathy is the most common phenotype in adults. The clinical data of a patient with adrenoleukodystrophy and spinal-peripheral neuropathy caused by a novel point mutation in exon 4 of the ABCD1 gene (c.1256T > G (p.Val419Gly)) were retrospectively analyzed. Furthermore, we constructed wild-type and mutant vectors of the ABCD1 (NM0000334) gene to validate the effect of this mutation on the expression of the ABCD1 gene and protein and to explore the mechanism of X-linked adrenoleukodystrophy occurrence and development to identify therapeutic targets for clinical treatment.

Relationship of irisin with disease severity and dopamine uptake in Parkinson's disease patients.

BACKGROUND: This study was designed to investigate the relationship of irisin with the severity of Parkinson's disease (PD) and dopamine (DOPA) uptake in patients with PD and to understand the role of irisin in PD. METHODS: The plasma levels of irisin and α-syn were measured by enzyme-linked immunosorbent assay (ELISA). Motor and nonmotor symptoms were assessed with the relevant scales. DOPA uptake was measured with DOPA positron emission tomography (PET)/magnetic resonance imaging (MRI). RESULTS: The plasma levels of α-syn and irisin in patients with PD gradually increased and decreased, respectively, with the progression of the disease. There was a negative correlation between plasma α-syn and irisin levels in patients with PD. The level of irisin in plasma was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS)-III scores and positively correlated with Montreal Cognitive Assessment (MoCA) scores. The striatal/occipital lobe uptake ratios (SORs) of the ipsilateral and contralateral caudate nucleus and anterior and posterior putamen in the high-irisin group were significantly higher than those in the low-irisin group, and irisin levels in the caudate nucleus and anterior and posterior putamen contralateral to the affected limb were lower than those on the ipsilateral side. The level of irisin was positively correlated with the SORs of the ipsilateral and contralateral caudate nucleus and putamen in PD patients. CONCLUSIONS: Irisin plays a neuroprotective role by decreasing the level of α-syn. Irisin is negatively correlated with the severity of motor symptoms and cognitive impairment. More importantly, irisin can improve DOPA uptake in the striatum of patients with PD, especially on the side contralateral to the affected limb.

Betulinic acid inhibits cell proliferation and fibronectin accumulation in rat glomerular mesangial cells cultured under high glucose condition.

Glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation have been recognized as major pathogenic events in the progression of diabetic nephropathy. Betulinic acid (BA), (3ß-hydroxy-lup-20(29)-en-28-oic acid), is a naturally occurring pentacyclic lupane group triterpenoid, and it has been shown to possess glucose-lowering property. However, the role of BA on MC proliferation and ECM accumulation in diabetic condition remains unclear. So, in the present study, we investigated the role of BA on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. In the current study, we demonstrated that BA suppressed HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21(Waf1/Cip1) and p27(Kip1). It also suppressed HG-induced fibronectin (FN) expression in MCs. Furthermore, BA inhibited HG-induced phosphorylation of ERK1/2 and p38MAPK in MCs. In conclusion, our present study demonstrated that BA inhibited HG-induced cell proliferation and FN expression in MCs via inhibiting ERK1/2 and p38MAPK pathways. Thus, BA may serve as a potential drug for the treatment of diabetic nephropathy.