Association analysis of dopaminergic degeneration and the neutrophil-to-lymphocyte ratio in Parkinson's disease.

Introduction: Peripheral inflammatory responses are suggested to play a major role in the pathophysiology of Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR), a new recognized biomarker, can reflect peripheral inflammation in PD. However, the association between the NLR and dopaminergic degeneration in PD remains unclear. Methods: In this retrospective study, 101 enrolled PD patients were categorized into early-stage and advanced-stage PD based on the Hoehn and Yahr (HY) scale. We evaluated the clinical characteristics, peripheral immune profile, and 11C-CFT striatal dopamine transporter (DAT) binding levels. Linear regression analyses were employed to assess the associations between NLR and striatal DAT levels at different stages in PD patients. Results: Covariate-controlled regression analysis revealed that higher NLR was significantly associated with lower DAT levels in the caudate (ß = -0.27, p = 0.003) and the putamen (ß = -0.27, p = 0.011). Moreover, in the early-stage PD subgroup, a similar association was observed (caudate: ß = -0.37, p = 0.013; putamen: ß = -0.45, p = 0.005). The lymphocytes count was correlated positively with the striatal DAT levels in the Spearman correlation analysis whether in total patients (caudate: ρ = 0.25, p = 0.013; putamen: ρ = 0.22, p = 0.026) or in the early-stage subgroup (caudate: ρ = 0.31, p = 0.023, putamen: ρ = 0.34, p = 0.011). Conclusion: Dopaminergic degeneration is associated with peripheral inflammation in PD. The NLR, a widely used inflammatory marker, may have the potential to reflect the degree of dopaminergic degeneration in individuals with early-stage PD.

Neuromelanin-sensitive magnetic resonance imaging: Possibilities and promises as an imaging biomarker for Parkinson's disease.

Parkinson's disease (PD) is an age-related progressive neurodegenerative disorder characterized by both motor and non-motor symptoms resulting from the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and noradrenergic neurons in the locus coeruleus (LC). The current diagnosis of PD primarily relies on motor symptoms, often leading to diagnoses in advanced stages, where a significant portion of SNpc dopamine neurons has already succumbed. Therefore, the identification of imaging biomarkers for early-stage PD diagnosis and disease progression monitoring is imperative. Recent studies propose that neuromelanin-sensitive magnetic resonance imaging (NM-MRI) holds promise as an imaging biomarker. In this review, we summarize the latest findings concerning NM-MRI characteristics at various stages in patients with PD and those with atypical parkinsonism. In conclusion, alterations in neuromelanin within the LC are associated with non-motor symptoms and prove to be a reliable imaging biomarker in the prodromal phase of PD. Furthermore, NM-MRI demonstrates efficacy in differentiating progressive supranuclear palsy (PSP) from PD and multiple system atrophy with predominant parkinsonism. The spatial patterns of changes in the SNpc can be indicative of PD progression and aid in distinguishing between PSP and synucleinopathies. We recommend that patients with PD and individuals at risk for PD undergo regular NM-MRI examinations. This technology holds the potential for widespread use in PD diagnosis.

Evaluation of risk factors for impulse control disorder in Parkinson's disease in northern China.

Introduction: Impulse control disorder (ICD) is a common non-motor symptom of Parkinson's disease (PD), but its risk factors are still controversial. This study aimed to determine the prevalence of ICD in northern China and analyze the risk factors associated with ICD, multiple ICDs, and four subtypes. Methods: A total of 285 PD patients were enrolled in this study. Each patient was screened using the Questionnaire for Impulse and Compulsive Control Disorders (QUIP). Stepwise regression analysis was performed to identify independent risk factors, and a prediction model was developed. Results: The prevalence of ICD in the study population was 11.6%. Stepwise regression analysis showed that ICD was associated with disease duration, motor symptoms, dyskinesia, depression, REM sleep behavior disorder (RBD) and cognitive decline; multiple ICDs were related to coffee history, motor symptoms, dyskinesia, depression, apathy and RBD. The prediction model demonstrated good performance with AUC values of 0.93, 0.88, and 0.66 on the balanced train set, balanced test set, and the original imbalanced data set, respectively. Conclusion: The risk factors for PD-ICD are complex and influenced by regional economic and cultural backgrounds. Clarifying these factors and developing predictive models can help to delay or even prevent the development of ICD through early screening and intervention.

Collagen-coated agarose-chitosan scaffold used as a skin substitute.

A single biomaterial is disadvantageous for constructing skin in vitro, so a mixed biomaterial is more conducive to skin research. In this study, agarose-chitosan scaffolds with a final concentration of 4% were constructed by freeze-drying, in which the concentration ratios of agarose to chitosan were 1:3, 2:2, and 3:1. The scaffolds were coated with a 3 mg/ml collagen solution, and the mechanical properties were evaluated by studying density, porosity, swelling rate, and degradation rate. The results demonstrated that the agarose-chitosan scaffolds were porous, with porosity reaching 93%. Their densities ranged from 0.1 to 0.16 g/cm3 . Analysis of Young's modulus showed that the mechanical properties of the agarose-chitosan scaffolds were significantly enhanced when the agarose content in the agarose-chitosan scaffolds was increased. Moreover, the density and Young's modulus of the agarose-chitosan scaffolds of different concentration ratios were significantly different (p < 0.01). These scaffolds can withstand a certain amount of external pressure, such as that of human skin, making them more suitable for further skin replacement research. In addition, the results of thiazolyl blue tetrazolium bromide (MTT) cell assay and immunofluorescence staining showed that the collagen-coated agarose-chitosan scaffolds were conducive to keratinocyte proliferation and differentiation. The MTT results revealed significant differences between the agarose-chitosan scaffolds coated with collagen and the agarose-chitosan scaffolds without collagen (p < 0.05). This study provides the potential for in vitro skin research and applications.

Photo-crosslinked hydrogels for tissue engineering of corneal epithelium.

The vast majority of patients with corneal blindness cannot recover their vision due to the serious shortage of donor cornea. However, the technology to construct a feasible corneal substitute is a promising treatment method for corneal blindness. In this paper, methacrylated gelatin (GelMA)-methacrylated hyaluronic acid (HAMA) double network (GHDN) hydrogels were prepared by modifying gelatin and hyaluronic acid with methacrylate anhydride (MA). GHDN hydrogel was compared with GelMA single network and HAMA single network hydrogels through characterization experiments of mechanical properties, optical properties, hydrophilicity and in-situ degradation in vitro. At the same time, the biocompatibility of hydrogel was tested by inoculating rabbit corneal epithelial cells (CEpCs) epidermal cells on hydrogels using CCK-8 test, live/dead staining, immunofluorescence staining and qRT-PCR. It was found that the GHDN hydrogel has optical transparency in the visible region, and its mechanical properties are better than those of GelMA and HAMA hydrogels, and its hydrophilicity is similar to that of normal human corneas. The results of in vitro hydrogel culture of CEpCs showed that the proliferation of CEpCs on GHDN hydrogel was two times higher than that of HAMA hydrogel, and the expression of specific marker Cytokeratin 3 (CK3) and Cytokeratin 12 (CK12) could be better maintained on GHDN hydrogel. All the experimental results proved that GHDN hydrogel has good physical properties and biocompatibility and is a potential candidate for corneal tissue engineering scaffolds.

Biocompatible chitosan/polyethylene glycol/multi-walled carbon nanotube composite scaffolds for neural tissue engineering.

Carbon nanotube (CNT) composite materials are very attractive for use in neural tissue engineering and biosensor coatings. CNT scaffolds are excellent mimics of extracellular matrix due to their hydrophilicity, viscosity, and biocompatibility. CNTs can also impart conductivity to other insulating materials, improve mechanical stability, guide neuronal cell behavior, and trigger axon regeneration. The performance of chitosan (CS)/polyethylene glycol (PEG) composite scaffolds could be optimized by introducing multi-walled CNTs (MWCNTs). CS/PEG/CNT composite scaffolds with CNT content of 1%, 3%, and 5% (1%=0.01 g/mL) were prepared by freeze-drying. Their physical and chemical properties and biocompatibility were evaluated. Scanning electron microscopy (SEM) showed that the composite scaffolds had a highly connected porous structure. Transmission electron microscope (TEM) and Raman spectroscopy proved that the CNTs were well dispersed in the CS/PEG matrix and combined with the CS/PEG nanofiber bundles. MWCNTs enhanced the elastic modulus of the scaffold. The porosity of the scaffolds ranged from 83% to 96%. They reached a stable water swelling state within 24 h, and swelling decreased with increasing MWCNT concentration. The electrical conductivity and cell adhesion rate of the scaffolds increased with increasing MWCNT content. Immunofluorescence showed that rat pheochromocytoma (PC12) cells grown in the scaffolds had characteristics similar to nerve cells. We measured changes in the expression of nerve cell markers by quantitative real-time polymerase chain reaction (qRT-PCR), and found that PC12 cells cultured in the scaffolds expressed growth-associated protein 43 (GAP43), nerve growth factor receptor (NGFR), and class III ß|-tubulin (TUBB3) proteins. Preliminary research showed that the prepared CS/PEG/CNT scaffold has good biocompatibility and can be further applied to neural tissue engineering research.

Preparation and In Vitro Characterization of Gelatin Methacrylate for Corneal Tissue Engineering.

BACKGROUND: Corneal disease is second only to cataract considered as the leading cause of blindness in the world, with high morbidity. Construction of corneal substitutes in vitro by tissue engineering technology to achieve corneal regeneration has become a research hotspot in recent years. We conducted in-depth research on the biocompatibility, physicochemical and mechanical properties of rat bone marrow mesenchymal stem cells (rBM-MSCs)-seeded gelatin methacrylate (GelMA) as a bioengineered cornea. METHODS: Four kinds of GelMA with different concentrations (7, 10, 15 and 30%) were prepared, and their physic-chemical, optical properties, and biocompatibility with rBM-MSCs were characterized. MTT, live/dead staining, cell morphology, immunofluorescence staining and gene expression of keratocyte markers were performed. RESULTS: 7%GelMA hydrogel had higher equilibrium water content and porosity, better optical properties and hydrophilicity. In addition, it is more beneficial to the growth and proliferation of rBM-MSCs. However, the 30%GelMA hydrogel had the best mechanical properties, and could be more conducive to promote the differentiation of rBM-MSCs into keratocyte-like cells. CONCLUSION: As a natural biological scaffold, GelMA hydrogel has good biocompatibility. And it has the ability to promote the differentiation of rBM-MSCs into keratocyte-like cells, which laid a theoretical and experimental foundation for further tissue-engineered corneal stromal transplantation, and provided a new idea for the source of seeded cells in corneal tissue engineering.

Construction of tissue-engineered skin with rete ridges using co-network hydrogels of gelatin methacrylated and poly(ethylene glycol) diacrylate.

Tissue-engineered skin, as a promising skin substitute, can be used for in vitro skin research and skin repair. However, most of research on tissue-engineered skin tend to ignore the rete ridges (RRs) microstructure, which enhances the adhesion between dermis and epidermis and provides a growth environment for epidermal stem cells. Here, we prepared and characterized photocurable gelatin methacrylated (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) co-network hydrogels with different concentrations. Using a UV curing 3D printer, resin molds were designed and fabricated to create three-dimensional micropatterns and replicated onto GelMA-PEGDA scaffolds. Human keratinocytes (HaCaTs) and human skin fibroblasts (HSFs) were co-cultured on the hydrogel scaffold to prepare tissue-engineered skin. The results showed that 10%GelMA-2%PEGDA hydrogel provides the sufficient mechanical properties and biocompatibility to prepare a human skin model with RRs microstructure, that is, it presents excellent structural support, suitable degradation rate, good bioactivity and is suitable for long-term culturing. Digital microscope image analyses showed the micropattern was well-transferred onto the scaffold surface. Both in vitro and in vivo experiments confirmed the formation of the epidermal layer with undulating microstructure. In wound healing experiments, hydrogel can significantly accelerate wound healing. This study provides a simple and powerful way to mimic the structures of human skin and can make a contribution to skin tissue engineering and wound healing.

Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease.

Neuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

Genetic Interaction of H19 and TGFBR1 Polymorphisms with Risk of Epilepsy in a Chinese Population.

PURPOSE: Long non-coding RNA H19 was highly expressed in the latent period of epilepsy, contributing to apoptosis of hippocampal neurons by targeting let-7b. Transforming growth factor beta receptor 1 (TGFBR1), a target of let-7b, is located on the susceptibility locus for epilepsy. In this context, we investigated the association between tagSNPs in long non-coding RNA H19 and transforming growth factor beta receptor 1 (TGFBR1) rs6478974 and the risk of epilepsy. PATIENTS AND METHODS: The present study consisted of 302 patients with epilepsy and 612 age- and gender-matched controls. The polymorphisms were analyzed using a TaqMan allelic genotyping assay. H19 and TGFBR1 mRNA levels were determined using quantitative real-time polymerase chain reaction. RESULTS: The TGFBR1 AT and TT genotypes emerged as a protective factor for the risk of epilepsy (AT vs AA: adjusted OR = 0.59, 95% CI: 0.39-0.89, P = 0.01; TT vs AA: adjusted OR = 0.53, 95% CI: 0.35-0.80, P = 0.002, respectively). The protective effect was also observed in recessive genetic model (adjusted OR = 0.56, 95% CI: 0.38-0.82, P = 0.003). Individuals carrying the rs6478974 TT genotype had lower levels of TGFBR1 mRNA. Moreover, the TCTAT and TCCAA haplotypes emerged as a risk factor for epilepsy and the rs3741219-rs2839698-rs6478974 was associated with an interactive effect on the risk of epilepsy. CONCLUSION: The current study provides evidence of the rs6478974 TT genotype decreasing the susceptibility to epilepsy by reducing the levels of TGFBR1 mRNA.

Analysis of factors associated with brittle response in patients with Parkinson's disease.

INTRODUCTION: The brittle response (BR) in patients with Parkinson's disease (PD) refers to a special type of levodopa-induced dyskinesia (LID). This study aimed to describe the clinical characteristics of BR patients and to analyze the associated risk factors. METHODS: A retrospective study was conducted to analyze the data of 97 patients with PD. Patients were divided into a BR group and a non-brittle response (NBR) group. Demographic and clinical data, motor symptoms, and non-motor symptoms of the two groups were assessed. RESULTS: Among 97 PD patients, 11 were in the BR group and 86 were in the NBR group. The proportion of female patients was 72.7% and 38.3%, respectively, in the BR and NBR groups (P < 0.05). Compared to NBR patients, BR patients had relatively low body weight, low BMI, long disease duration, high levodopa equivalent daily dosage (LEDD), and high levodopa dose per weight (P < 0.05). The BR group had significantly higher scores of UPDRS (II, III, and IV) (P < 0.05). But no difference was found in the UPDRS I, emotional state, cognitive status, and accompanied by REM sleep behavior disorder (RBD) (P> 0.05). Multivariate logistic regression analysis showed that BR patients had lower body weight and higher levodopa dose per weight. CONCLUSION: BR is associated with being female, low body weight, low BMI, long disease duration, high LEDD, and high levodopa dose per weight. Body weight and levodopa dose per body weight are independent risk factors for BR.

Spinocerebellar ataxia 2 in a family with different phenotypes: Two case reports.

RATIONALE: Spinocerebellar ataxia 2 (SCA2) is a genetic disease, mainly characterized by ataxia. A number of other neurological symptoms also have been described, such as Parkinsonism, cognitive dysfunction, autonomic dysfunction, even the signs of motor neuron disease and so on. Mostly, In the same family, clinical performance is the same in most cases. Here, we describe a father and his son who suffered from SCA2, but their first manifestations were different. PATIENT CONCERNS: The father exhibited progressive bradykinesia and rigidity, which resulted in the dysfunction of walking and caring himself. He hoped to relieve his symptoms by taking medicine. But the son presented with ataxia which was mild that the discomfort did not affect his daily life with none treated. DIAGNOSIS: Both of them were given SCA2 tests. Briefly, we designed primers around the CAG trinucleotide, repeated the spinal cerebellar ataxia subtype gene, performed PCR expansion, and then calculated the specific number of repetitions by capillary electrophoresis. Abnormal expansion was detected in them through SCA2 sequencing with different repeat numbers of CAG, and then they were diagnosed with SCA2 sequencing. INTERVENTIONS: The father was treated with dopaminergic drugs, but the son was not administered treatment. OUTCOMES: The father's symptoms are improved and he can take care of himself. The son has none difficulty in his daily life. LESSONS: It is rare that different individuals in the same family with SCA2 have different manifestations. The genetic testing is a crucial method to diagnose the disease of SCA2.

The correlation between possible RBD and cognitive function in Parkinson's disease patients in China.

OBJECTIVE: Cognitive impairment is an important symptom of Parkinson's disease (PD) and seriously affects patients' quality of life and prognosis. However, its cause is still uncertain. In about one-third of patients, PD is associated with rapid eye movement sleep behavior disorder (RBD), which is an independent risk factor for PD-associated dementia; but whether or not it relates to the cognitive function of patients with nondemented PD is still controversial. METHODS: The data from 89 enrolled PD patients were retrospectively analyzed. The RBD Questionnaire Hong-Kong (RBD-HK) was used to diagnose possible RBD (pRBD). There are 46 patients with possible RBD (the PD-pRBD) and 43 without (the PD-npRBD). PD disease severity, neuropsychological function, overall cognitive function, and various cognitive functions were assessed. RESULTS: There were significant between-group differences in scores on the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Digit Symbol Test (DST), Trail Making Test-A (TMT-A)-Time, TMT-Trail Making Test-B (TMT-B)-Time, Stroop Color-word Test, Clock Drawing Test (CDT), Boston Naming Test (BNT), Verbal Fluency Test (fruit), etc. (P < 0.05). INTERPRETATION: Patients in the PD-pRBD group had more cognitive impairment.

The role of Rho/Rho-kinase pathway and the neuroprotective effects of fasudil in chronic cerebral ischemia.

The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic cerebral ischemia. In this study, rat models of chronic cerebral ischemia were established by permanent bilateral common carotid artery occlusion and intragastrically administered 9 mg/kg fasudil, a powerful ROCK inhibitor, for 9 weeks. Morris water maze results showed that cognitive impairment progressively worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative RT-PCR and western blot analysis showed that the expression levels of Rho-kinase, its substrate myosin-binding subunit, and its related protein alpha smooth muscle actin, significantly increased after chronic cerebral ischemia. TUNEL staining showed that chronic cerebral ischemia could lead to an increase in neuronal apoptosis, as well as the expression level of caspase-3 in the frontal cortex of rats subjected to chronic cerebral ischemia. Fasudil treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, and decreased the expression level of Rho-kinase, myosin-binding subunit and alpha smooth muscle actin. Furthermore, fasudil could regulate cerebral injury by reducing cell apoptosis and decreasing caspase-3 expression in the frontal cortex. These findings demonstrate that fasudil can protect against cognitive impairment induced by chronic cerebral ischemia via the Rho/Rho-kinase signaling pathway and anti-apoptosis mechanism.

Hemichorea associated with non-ketotic hyperglycaemia: a case report.

Hemichorea is a rare complication of non-ketotic hyperglycaemia. Patients with this syndrome have classically longstanding, poorly controlled diabetes. Here, we report a patient presenting hemichorea without diabetic history. His symptom resolved rapidly after correction of hyperglycaemia. We suggest that hemichorea may be the first manifestation of undiagnosed diabetes.

Quality of life and its influencing factors in patients with post-traumatic epilepsy.

OBJECTIVE: To observe the quality of life in patients with post-traumatic epilepsy and discuss the influencing factors. METHODS: We assessed 105 patients with post-traumatic epilepsy and 100 healthy people as control using Quality of Life Scale-31 (QOL-31), Self-rating Depressing Scale (SDS) and Self-rating Anxiety Scale (SAS), and conducted retrospective analysis on the depression, anxiety, site of trauma, control of seizure, EEG and therapeutic compliance. RESULTS: Patients with post-traumatic epilepsy scored much lower than the control group on QOL-31 (P less than 0.01), but higher than the control group on SDS and SAS (P less than 0.01). Multiple regression analysis indicated that major influencing factors on the quality of life were anxiety, therapeutic compliance, depression, poor control of epileptic seizure and site of trauma. CONCLUSIONS: The quality of life in patients with post-traumatic epilepsy has significantly declined. Doctors should pay attention to psychological and mental problems of patients with epilepsy, such as depression and anxiety, enhancing therapeutic compliance and controlling epileptic seizure, which are the keys to improving prognosis.