[Influential factors of non-motor symptoms prognosis in Parkinson's disease patients undergoing deep brain stimulation].

Objective: To investigate the effects of electrode activated contact location, volume of tissue activated (VTA) and age on non-motor symptoms, such as emotional symptoms and cognitive function, in Parkinson's disease (PD) patients with deep brain stimulation (DBS). Methods: PD patients who underwent DBS of subthalamic nucleus (STN) at the Department of Functional Neurosurgery of Beijing Tiantan Hospital from September 1, 2020 to August 31, 2022 were retrospectively enrolled. The International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination Scales (MMSE) were used at the preoperative, 1-month and 12-month postoperative time points. In this study, patients were divided into middle-aged (age<60 years,n=39) and elderly (age≥60 years,n=62) groups to investigate the effect of age factor on the clinical outcome of surgery. Lead-DBS software was used to convert the patients' electrode reconstruction results into Montreal standard space, and the patients were divided into sensorimotor(n=43) and combined groups(n=53) according to the distribution of activation contact locations in the subzones of the STN. In addition, the patients were divided into a cognitive improvement group(n=57)and a cognitive deterioration group(n=44) based on the results of MoCA at 12 months. The positional information of the electrode activation contacts was collected and the VTA was calculated to analyze the effects on electrode activation electroshock location and activated tissue volume on patients' non-motor symptoms. Results: A total of 101 patients with PD were enrolled, including 46 males and 55 females, aged (62.6±8.4) years. Middle-aged patients had significantly higher MoCA scores, delayed recall scores, attention scores, and naming scores than older patients at 12 months postoperatively (all P<0.05). At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score were -1.77%±20.36%, 39.65%±42.91% and 36.23%±45.45% respectively in sensorimotor group. At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score was 11.69%±22.24%, 16.62%±68.10% and 2.30%±95.04% respectively in the combined group, and the difference between the two groups was statistically significant (MoCA: P=0.002; HAMA: P=0.040; HAMD: P=0.033) The distribution of VTA in the sensory motor area and marginal area of the left hemisphere STN in patients with improved cognitive function was significantly smaller than that in the deterioration group [(60.53±52.04)mm³vs (84.55±61.00)mm³, P=0.035; (41.81±33.36)mm³vs (59.05±45.46)mm³, P=0.030]. Conclusion: The effect of STN-DBS on emotional symptoms and cognitive function in PD patients is influenced by various factors and is closely related to the patient's age, electrode activation contact location and VTA.

[Statistical parametric mapping analysis of 18F-FDG PET in Parkinson's disease with mild cognitive impairment].

Objective: To investigate the characteristics of cerebral metabolism associated with mild cognitive impairment (MCI) Parkinson's disease (PD), cognitive normal PD and normal control to find a PET biomarker for the diagnose and estimate of PD-MCI. Methods: Forty-seven patients diagnosed with PD (included 15 with mild cognitive impairment) and 20 control subjects were enrolled. All the subjects were evaluated with FDG-PET and clinical scale. The statistical parametric mapping (SPM) were analyzed to determine metabolic patterns that may be useful in differentiating between the three groups. Results: SPM analysis showed that significant hypometabolism were observed in both side of front lobe, parietal lobe, left temporal lobe and left occipital lobe; in the contrast, the relative hypermetabolism had been observed in the cerebellum, vermis, hippocampus and supplement motor area (SMA) in patients with PD-MCI. PD without MCI showed hypometabolism in both side of front lob, caudate and putamen. PD-MCI showed that the significant hypermetabolism were in the insular and cerebellum while hypometabolism were in the both side of occipital compared to PD without MCI. Conclusion: A voxel-by-voxel based SPM method i. e. SPM8 analysis by PET scan is an effective way to analysis the FDG uptake pattern of PD patients. The hypermetabolism in the insula and cerebellum and hypometabolism in the both side of occipital may be a biomarker for make a diagnosis of PD-MCI.

Chondrogenesis of mesenchymal stem cells in a novel hyaluronate-collagen-tricalcium phosphate scaffolds for knee repair.

Scaffolds are expected to play a key role in the induction of chondrogenesis of mesenchymal stem cells (MSCs) for cartilage tissue regeneration. Here, we report the development of a novel tricalcium phosphate-collagen-hyaluronate (TCP-COL-HA) scaffold that can function as a stem cell carrier to induce chondrogenesis and promote cartilage repair, and the investigation of chondroinductive properties of scaffolds containing varying amounts of TCP, COL and HA. TCP-COL-HA scaffolds, as well as TCP-COL scaffolds at two different TCP/COL ratios (50:50 and 25:75), were evaluated for their ability to induce cartilage regeneration from rabbit mesenchymal stem cells (rMSCs) in vitro and in vivo. Chondrogenic differentiation was evaluated by sulphated glycosaminoglycan quantification, collagen type II immunohistochemistry, and qRT-PCR. Mechanical strength was evaluated by the compression test. The results showed that the TCP-COL-HA scaffolds enhanced rMSC chondrogenesis to a greater degree than did the TCP-COL scaffolds; for the latter, the scaffold with the lower TCP/COL ratio (25:75) was superior in terms of promoting rMSC chondrogenesis. Similar results were obtained in an ectopic implantation model in nude mice. In a critical-size rabbit osteochondral defect-repair model, rMSCs seeded on TCP-COL-HA scaffolds showed greater cartilage regeneration and integration into surrounding tissue than the TCP-COL groups, in which cartilage repair was more efficient at the 25:75 than at the 50:50 ratio. These results indicate that the addition of HA and different TCP/COL ratios can affect the chondroinductive capacity of scaffolds, and suggest that the TCP-COL-HA scaffold can serve as an effective cell carrier for cartilage regeneration.

Effects of the consumption of rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric Kaschin-Beck disease: an epidemiological intervention trial in the Qinghai Province.

OBJECTIVE: Based on the aetiological hypothesis of Kaschin-Beck disease (KBD), different interventions were adopted, and the preventive and therapeutic effects of interventions was observed and evaluated in this trial. DESIGN: A total of 358 children from seven villages of Qinghai Province in China were examined, and 280 children aged 6-11 years old were eligible for the trial. The children were divided into three groups that received either no intervention (n = 64), 150 kg/person of rice from non-KBD areas (n = 103) or 7 kg/family of selenium-iodine salt (n = 113) for 12 months. Data were collected and used to calculate the proportion of patients with X-ray lesions, the proportion of new patients and the metaphyseal repair rate. All indicators were analysed with Pearson chi-square or Fisher's exact tests. The registration number of this trial is ChiCTR-PNRC-12002309 (http://www.chictr.org). RESULTS: After interventions, the proportion of patients with X-ray lesions increased dramatically in the control group and decreased significantly in two intervention groups; significant differences were seen between the control group and two intervention groups (P < 0.05). Moreover, significant differences were observed in the proportions of new patients and the metaphyseal repair rates between the control group and two intervention groups (P < 0.05). Additionally, the proportion of new patients was lowest and the metaphyseal repair rate was highest in group B. CONCLUSIONS: The effects of eating rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric KBD were notable, the consumption of rice might be the most effective and safest intervention and should be encouraged.

Down-regulation of miR-124 target protein SCP-1 inhibits neuroglioma cell migration.

OBJECTIVE: MicroRNAs (miRNAs) have been widely studied as a potential cancer agent, but its efficacy does not get improvement due to poor targeting. miRNAs have been reported to play multiple roles in the development of the tumor. miR-124 is expressed in various tumor. This study aimed to elucidate the expression of miR-124 in neuroglioma cells as well as its related mechanism. MATERIALS AND METHODS: Expression of miR-124 in neuroglioma cells was assessed by Quantitative PCR (q-PCR). Astrocytes (RA cells) were used as control group. The relationship between miR-124 and SCP-1 was explored with bioinformatics tools. Luciferase reporter assay was performed to examine the expression of miR-124 target protein SCP-1. Gene interference technology was used to regulate expression of miR-124 and SCP-1 in neuroglioma cells, and q-PCR was performed to confirm gene interference effects. Migration of miR-124 and SCP-1 in neuroglioma cell was measured by wound healing assay and cell migration test. RESULTS: Compared with control group, the expressions of miR-124 (p=0.0015) and SCP-1 (p=0.0042) were higher in neuroglioma cells. Luciferase reporter assay proved that SCP-1 was the target of miR-124. Wound healing assay and migration test showed down-regulation of SCP-1 inhibited neuroglioma cell migration. Down-regulation of miR-124 didn't influence neuroglioma cell migration movement. CONCLUSIONS: miR-124 and SCP-1 in neuroglioma cell were highly expressed. MiR-124 impeded the progression of neuroglioma via down-regulating SCP-1.

MiR-508-5p is a prognostic marker and inhibits cell proliferation and migration in glioma.

OBJECTIVE: Increasing evidence has informed that dysregulation of microRNAs (miRNAs) may contribute to carcinogenesis in human. The aim of the present study was to determine the role of miR-508-5p in glioma. PATIENTS AND METHODS: Quantitative real-time PCR was performed to detect the expression levels of miR-508-5p in glioma and normal control tissues. In vitro, migration assays and a wound-healing assay were performed to determine the effects of miR-508-5p. Associations between miR-508-5p expressions and various clinicopathological characteristics were analyzed. Survival rate was determined with Kaplan-Meier. Univariate and multivariate analyses were performed to estimate the effects of the expression of miR-508-5p on survival. RESULTS: The expression of miR-508-5p was downregulated in glioma tissues and cell lines. Low miR-508-5p expression was related to WHO grade (p = 0.005) and KPS score (p = 0.013). Moreover, Kaplan-Meier survival analysis showed that low miR-508-5p expression was significantly associated with short overall survival (p = 0.0059). Furthermore, multivariate analysis revealed that miR-508-5p was an independent prognostic factor for the overall survival in glioma (p = 0.002). Finally, forced expression of miR-508-5p could inhibit glioma cell growth and metastasis in vitro. CONCLUSIONS: Taken together, our study suggested that miR-508-5p may be served as a novel prognostic factor and may lead to new treatment strategies for glioma.

Effects of acrylamide on creatine kinase from rabbit muscle.

The mechanism of inhibition of creatine kinase (CK) by acrylamide (Acr) has been examined (in vitro). Within the concentration range of 0 to 1 M, Acr markedly inhibited CK and depleted the protein thiols. Both inactivation and thiol depletion were time- and Acr concentration-dependent. Addition of dithiothreitol (DTT) did not reactivate CK inactivated by Acr. However, CK with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) pre-blocked thiols can be reactivated by DTT after incubation with Acr. The transition-state analogue also had a significant protective effect on CK against Acr inhibition. We conclude that thiol alkylation is a critical event in inactivation of CK by Acr. Furthermore, Acr binding to CK changed its surface charge, which may be the same effect for the toxicity of Acr towards other proteins.

Dissociation and unfolding of GCN4 leucine zipper in the presence of sodium dodecyl sulfate.

The dissociation and unfolding behavior of the GCN4 leucine zipper has been studied using SDS titration. Circular dichroism (CD) spectra showed that the alpha-helix content of the leucine zipper (20 microM) decreased during the sodium dodecyl sulfate (SDS) titration. However, the alpha-helix content of the leucine zipper still remained significant in the presence of 1 mM SDS, with little change detected when the SDS concentration further increased to 2 mM. The dimer dissociation of the leucine zipper is also a co-operative process during SDS titration; with no dimer remaining when SDS concentration reached 1 mM, as shown by electrophoresis and the the theta(222)/theta(208) ratio. Our results indicate that SDS efficiently induces leucine zipper dimer dissociation with the monomers still partially folded. The experimental results provide important evidence for the previous model that partial helix formation precedes dimerization in coiled coil folding.

High-frequency stimulation of the hippocampus protects against seizure activity and hippocampal neuronal apoptosis induced by kainic acid administration in macaques.

Kainic acid (KA) administration is known to cause seizures and neuronal death in the hippocampus. High-frequency stimulation (HFS) of the hippocampus can be a promising method in the treatment of epilepsy while the mechanism of action is unknown yet. It remains unknown whether HFS is neuroprotective for hippocampal neurons following KA-induced seizures in macaques, although HFS has neuroprotective effects in animal models of Parkinson's disease. We therefore examined the effects of HFS on KA-induced seizures and neuronal survival in macaque's hippocampus. Seizure frequency following KA that led to seizures in macaques was strongly reduced by HFS of the hippocampus. In addition, administration of KA led to marked neuronal apoptosis in the hippocampus, accompanied by increased levels of Bax, activated caspase-3 and decreased levels of Bcl-2. HFS was found to attenuate changes in apoptosis-related proteins and robustly decreased neuronal loss following KA administration. These data indicate that hippocampal HFS can protect hippocampal neurons against KA neurotoxicity, and that HFS neuroprotection is likely to operate with inhibition of apoptosis.

Evidence for the existence of an unfolding intermediate of thyroglobulin during denaturation by guanidine hydrochloride.

The unfolding of bovine thyroglobulin (Tg) in guanidine hydrochloride (GuHCl) solution was studied by following the fluorescence and circular dichroism. With increasing GuHCl concentrations, the emission maximum of the intrinsic fluorescence clearly red-shifted in two stages. At concentrations of GuHCl less than 1.2 M or more than 1.6 M, the red shift showed a cooperative manner. At concentrations of GuHCl between 1.2 and 1.6 M, an unfolding intermediate was observed. It was further characterized by the increased binding of the fluorescence probe 1-anilinonaphthalene-8-sulfonic acid (ANS). No significant changes of the secondary structure were indicated by CD spectra at the concentrations of GuHCl between 1.2 and 1.6 M. The conformation of this state has properties similar to those of a molten globule state which may exist in the folding pathway of the protein. Further changes in fluorescence properties occurred at concentrations of denaturant higher than 1.6 M with a significant red shift of the emission maximum from 340 to 347 nm and a marked decrease in ANS binding. This in vitro study gave a clue to understand the biochemical mechanism for the occurrence of aggregation and molecular chaperone binding during Tg maturation in vivo.