Hyperglycemia affects axial signs in patients with Parkinson's disease through mechanisms of insulin resistance or non-insulin resistance.

OBJECTIVE: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP). METHODS: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups. Correlations between levels of HbA1c and the homeostatic model assessment (HOMA)-IR and motor function in PWP were further analyzed. RESULTS: HbA1c level was significantly and positively correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score, axial signs subscore, the Timed Get Up and Go test time, the center of pressure displacement of standing with eyes open and closed, and significantly and negatively correlated with the 10-m walk test comfortable gait speed. HOMA-IR level was significantly and negatively correlated with 10-m walk test comfortable gait speed, but not with others. CONCLUSIONS: PWP with high HbA1c showed worse axial symptoms, including dysfunction of automatic walking, dynamic balance, and postural control than those with low HbA1c. In PWP, the effects of hyperglycemia on automatic walking speed may be associated with the IR-related mechanisms, and the effects on dynamic balance and postural control may be related to mechanisms other than IR.

The impact of cerebral small vessel disease burden and its imaging markers on gait, postural control, and cognition in Parkinson's disease.

OBJECTIVE: This study aimed to investigate how cerebral small vessel disease (CSVD) burden and its imaging markers are related to alterations in different gait parameters in Parkinson's disease (PD) and whether they affect attention, information processing speed, and executive function when global mental status is relatively intact. METHODS: Sixty-five PD patients were divided into the low CSVD burden group (n = 43) and the high CSVD burden group (n = 22). All patients underwent brain magnetic resonance imaging scans, clinical scale evaluations, and neuropsychological tests, as well as quantitative evaluation of gait and postural control. Multivariable linear regression models were conducted to investigate associations between CSVD burden and PD symptoms. RESULTS: Between-group analysis showed that the high CSVD group had worse attention, executive dysfunction, information processing speed, gait, balance, and postural control than the low CSVD group. Regression analysis revealed that greater CSVD burden was associated with poor attention, impaired executive function, and slow gait speed; white matter hyperintensity was associated with slow gait speed, decreased cadence, increased stride time, and increased stance phase time; the presence of lacune was associated only with poor attention and impaired executive function; enlarged perivascular space in the basal ganglia was associated with gait speed. CONCLUSIONS: CSVD burden may worsen gait, postural control, attention, and executive function in patients with PD, and different imaging markers play different roles. Early management of vascular risks and treatment of vascular diseases provide an alternate way to mitigate some motor and cognitive dysfunction in PD.

TMT-labeled quantitative proteomic analysis to identify proteins associated with the stability of peanut milk.

BACKGROUND: Peanut milk benefits human health mainly due to its high protein content and suitable amino acid composition. To reveal the molecular mechanism affecting the quality of peanut milk, tandem mass tag (TMT)-labeled proteomic analysis was applied to identify the proteome variation between two peanut cultivars that produced peanut milk with the best and worst stability. RESULTS: A total of 478 differentially abundant proteins (fold change >1.2 or <0.83, P < 0.05) were identified. Most of these proteins were located in the cytoplasm and chloroplasts. Correlation analysis showed that RNA recognition motif (RRM) domain-containing protein (17.1 kDa) had a negative relationship with the sedimentation rate of peanut milk and that 22.0 kDa class IV heat shock protein was negatively correlated with the creaming index (P < 0.05). Bioinformatic analysis showed that the molecular function of RRM domain-containing protein (17.1 kDa) was associated with RNA binding and nucleotide binding, and 22.0 kDa class IV heat shock protein was involved in the pathway of protein processing in the endoplasmic reticulum. CONCLUSION: Overall, the differentially abundant proteins in the biological metabolic pathway might offer some potential markers to guide future peanut breeding, especially for the production of peanut milk. © 2021 Society of Chemical Industry.

Correlations of apathy with clinical symptoms of Alzheimer's disease and olfactory dysfunctions: a cross-sectional study.

BACKGROUND: Apathy is one of the most common symptoms of Alzheimer's disease (AD), however, correlations of apathy with demographic variables, cognitive functions, neuropsychiatric symptoms, activity of daily living and olfactory functions in AD patients are still lacking comprehensive investigations. METHODS: This is a cross-sectional study. Total 124 typical AD patients were consecutively recruited from April 2014 to April 2017. In 124 AD patients, 47 cases (37.9%) were male and 77 cases were female; patients' age were 43-93 years with an average of 68 years. Patients were divided into AD with apathy (AD-A) and AD with no apathy (AD-NA) groups according to the score of Modified Apathy Evaluation Scale, then were evaluated cognitive functions, neuropsychiatric symptoms and activity of daily living, and tested olfactory functions. Above variables were compared between AD-A and AD-NA groups. Further correlation analyses and linear regression analysis were performed between apathy and above variables. RESULTS: Compared with AD-NA group, global cognitive level, verbal memory, verbal fluency and activity of daily living were significantly compromised in AD-A group (P < 0.002); depression and agitation were severely displayed in AD-A group (P < 0.002). Apathy was negatively correlated with global cognitive function, verbal memory, verbal fluency and activity of daily living (P < 0.05). There was no significant difference of olfactory functions between the two groups (P > 0.002), and correlations between apathy and olfactory threshold, olfactory identification and global olfactory function were significant (P < 0.05) but quite weak (|r| < 0.3). Further linear regression analysis showed that only verbal fluency and instrumental activities of daily living were independently associated with apathy. CONCLUSIONS: Independent correlations among apathy, verbal fluency and instrumental activities of daily living in AD patients might be related to the common brain area involved in their pathogeneses.

Novel ACE Inhibitory Peptides Derived from Simulated Gastrointestinal Digestion in Vitro of Sesame (Sesamum indicum L.) Protein and Molecular Docking Study.

The aim of this study was to isolate and identify angiotensin I-converting enzyme (ACE) inhibitory peptides from sesame protein through simulated gastrointestinal digestion in vitro, and to explore the underlying mechanisms by molecular docking. The sesame protein was enzymatically hydrolyzed by pepsin, trypsin, and α-chymotrypsin. The degree of hydrolysis (DH) and peptide yield increased with the increase of digest time. Moreover, ACE inhibitory activity was enhanced after digestion. The sesame protein digestive solution (SPDS) was purified by ultrafiltration through different molecular weight cut-off (MWCO) membranes and SPDS-VII (< 3 kDa) had the strongest ACE inhibition. SPDS-VII was further purified by NGC Quest™ 10 Plus Chromatography System and finally 11 peptides were identified by Nano UHPLC-ESI-MS/MS (nano ultra-high performance liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry) from peak 4. The peptide GHIITVAR from 11S globulin displayed the strongest ACE inhibitory activity (IC50 = 3.60 ± 0.10 µM). Furthermore, the docking analysis revealed that the ACE inhibition of GHIITVAR was mainly attributed to forming very strong hydrogen bonds with the active sites of ACE. These results identify sesame protein as a rich source of ACE inhibitory peptides and further indicate that GHIITVAR has the potential for development of new functional foods.

Effect of ultrasonic and ball-milling treatment on cell wall, nutrients, and antioxidant capacity of rose (Rosa rugosa) bee pollen, and identification of bioactive components.

BACKGROUND: Bee pollen has been regarded as a complete nutritional human dietary supplement but its nutrient absorption and biological effects may be restricted by the complex pollen wall. The aim of this study was to explore the effects of ultrasonic and ball-milling treatment on the release of nutritional components and on in vitro and in vivo antioxidant effects of rose (Rosa rugosa) bee pollen. RESULTS: Bee pollen walls were broken to varying degrees, nutrients were released, and in vitro and in vivo antioxidant effects of bee pollen were improved. The scavenging effects of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazolone-6-sulfonic acid) (ABTS) radicals, and oxygen radical absorbance capacity (ORAC) were improved. In aging mice, wall-breaking treatment led to better organ recovery, enhanced superoxide dismutase (SOD) and catalase (CAT) effects, and malondialdehyde (MDA) reduction. Eight compounds of rose bee pollen ethanol extract, including isorhamnetin 3-O-diglucoside and N', N″, N‴-dicaffeoyl p-coumaroyl spermidine were identified by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) assay. CONCLUSION: This study showed that ultrasonic treatment had greater wall-disruption effects of bee pollen on nutrient release and antioxidant effect promotion. In conclusion, rose bee pollen, with wall-breaking treatments, may have potential value as an ingredient in functional food processing. © 2019 Society of Chemical Industry.

Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

BACKGROUND: Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. METHODS: PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. RESULTS: PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the levels of transferrin and light-ferritin in serum and iron level in CSF were significantly elevated (P < 0.05), but ferroportin level in CSF was significantly decreased in PDSN+ group (P < 0.05). CONCLUSIONS: PD patients with hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

Clinical features and neurobiochemical mechanisms of olfactory dysfunction in patients with Parkinson disease.

This study aimed to investigate clinical features, influencing factors and neurobiochemical mechanisms of olfactory dysfunction (OD) in Parkinson disease (PD). Total 39 patients were divided into the PD with OD (PD-OD) and PD with no OD (PD-nOD) groups according to overall olfactory function, including threshold, discrimination and identification, assessed by Sniffin' Sticks test. Motor function and non-motor symptoms were rated by multiple scales. Dopamine, acetylcholine, norepinephrine and 5-hydroxytryptamine levels in cerebrospinal fluid (CSF) were measured. We found that the PD-OD group showed significantly lower score of Montreal Cognitive Assessment Scale, higher scores of rapid eye movement sleep behavior disorder (RBD) Screening Questionnaire and Epworth Sleepiness Scale than the PD-nOD group (p < 0.05). RBD Screening Questionnaire score was independently associated with the scores of overall olfactory function and discrimination (p < 0.05). Dopamine and acetylcholine levels in CSF from the PD-OD group was significantly lower than that from the PD-nOD group (p < 0.05). Dopamine and acetylcholine levels in CSF were significantly and positively correlated with the scores of overall olfactory function, threshold, discrimination and identification in PD patients (p < 0.05). RBD Screening Questionnaire score was significantly and negatively correlated with acetylcholine level in CSF in PD patients with poor olfactory detection (p < 0.05). This investigation reveals that PD-OD is associated with cognitive impairment, probable RBD and excessive daytime sleepiness. PD-OD is correlated with the decreased levels of dopamine and acetylcholine in CSF. RBD is an independent influencing factor of overall olfactory function and discrimination, and the decreased acetylcholine level in CSF may be the common neurobiochemical basis of RBD and OD in PD patients.

Association between nutritional status and gait performance in Alzheimer's disease.

AIMS: This study aimed to comprehensively explore the nutrition and gait of AD patients at different stages and the relationship between them. METHODS: A total of 85 AD patients were consecutively enrolled in this cross-sectional study and divided into the mild cognitive impairment (MCI) due to AD (AD-MCI) and the dementia due to AD (AD-D) groups. Demographic information, nutritional status, and gait performance were compared between the two groups, and the correlation between nutritional status and gait performance was subsequently analyzed by Pearson and Spearman correlation analyses. RESULTS: The AD-D group had lower scores on Mini-Nutritional Assessment (MNA) and MNAm scales, lower levels of urea nitrogen, folic acid, and vitamin B12 in blood, and higher homocysteine level than those in the AD-MCI group (all p < 0.05). The AD-D group had slower step speed, shorter step length, and shorter stride length than those in the AD-MCI group (all p < 0.05). AD patients with decreased scores of MNA and MNAm scales, and declined levels of urea nitrogen and vitamin B12 in blood had reduced gait speed and gait cadence, and prolonged step length time and stride length time, whereas homocysteine showed the almost opposite results (all p < 0.05). In the AD-MCI group, the score of scale was negatively correlated with the coefficient of variation (CV) of stride length, and the folic acid level was negatively correlated with the CV of stride length and cadence (all p < 0.05). CONCLUSIONS: AD patients at the dementia stage had worse nutritional status and gait performance than those at the MCI stage, which was associated with worse global cognition and activities of daily living. Poorer nutritional status was associated with higher gait variability in patients at the MCI stage and with poorer gait performance in patients at the dementia stage. Early identification and intervention of patients with nutritional risk or malnutrition may improve gait performance, thus reducing the risk of falling and cognitive decline, as well as the mortality.

An investigation into the potential association between nutrition and Alzheimer's disease.

Background: Malnutrition is the most common nutritional issue in Alzheimer's disease (AD) patients, but there is still a lack of a comprehensive evaluation of the nutritional status in AD patients. This study aimed to determine the potential association of various nutritional indices with AD at different stages. Methods: Subjects, including individuals with normal cognition (NC) and patients diagnosed with AD, were consecutively enrolled in this cross-sectional study. Demographics, body composition, dietary patterns, nutritional assessment scales and nutrition-related laboratory variables were collected. Binary logistics regression analyses and receiver operating characteristic (ROC) curves were used to indicate the association between nutrition-related variables and AD at different stages. Results: Totals of 266 subjects, including 73 subjects with NC, 72 subjects with mild cognitive impairment due to AD (AD-MCI) and 121 subjects with dementia due to AD (AD-D) were included. There was no significant difference in dietary patterns, including Mediterranean diet and Mediterranean-DASH diet intervention for neurodegenerative delay (MIND) diet between the three groups. Lower BMI value, smaller hip and calf circumferences, lower Mini Nutritional Assessment (MNA) and Geriatric Nutritional Risk Index (GNRI) scores, and lower levels of total protein, albumin, globulin, and apolipoprotein A1 were associated with AD (all p < 0.05). Total protein and albumin levels had the greatest ability to distinguish AD from non-AD (AUC 0.80, 95% CI 0.74-0.84, p < 0.001), increased by combining calf circumference, MNA score and albumin level (AUC 0.83, 95% CI 0.77-0.88, p < 0.001). Albumin level had the greatest ability to distinguish NC from AD-MCI (AUC 0.75, 95% CI 0.67-0.82, p < 0.001), and MNA score greatest ability to distinguish AD-MCI from AD-D (AUC 0.72, 95% CI 0.65-0.78, p < 0.001). Conclusion: Nutritional status of AD patients is significantly compromised compared with normal controls, and tends to be worsened with AD progresses. Early identification and intervention of individuals with nutritional risk or malnutrition may be significantly beneficial for reducing the risk, development, and progression of AD.

Lacunes may worsen cognition but not motor function in Parkinson's disease.

BACKGROUND: As one of the imaging markers of cerebral small vessel disease, lacunes has received little attention. The objective of this study was to investigate the associations of lacunes, cognition and motor function in patients with Parkinson's disease (PD) and whether these associations are independent of other imaging markers. METHODS: Patients were consecutively included from April 2019 to July 2022 in Beijing Rehabilitation Hospital. All patients underwent brain magnetic resonance imaging scans, clinical scale evaluations, and neuropsychological tests, as well as quantitative evaluation of postural control. To eliminate the possible factors contributing to cognition and motor dysfunction in patients with PD, in particular white matter hyperintensities and enlarged perivascular space in the basal ganglia, multivariate linear regression models were constructed to sort out the effect of lacunes. RESULTS: Ninety-four patients were included in this study, 56 without lacunes and 38 with lacunes. Patients with lacunes showed shorter disease duration, slower gait speed and spent more time on Trail-Making Test part A (TMT-A) than those without lacunes. The number of lacunes were positively correlated with the time to complete the TMT-A and negatively related to gait speed. Multivariate linear regression models showed that the presence of lacunes was associated with longer TMT-A time after adjusting for potential confounders. CONCLUSIONS: Lacunes were independently associated with worse visual scanning, attention, and processing speed in patients with PD. In addition, lacunes may accelerate the course of PD. Early treatment of vascular disease provides an alternate way to mitigate some motor and cognitive dysfunction in patients with PD.

Lacunes were independently associated with worse visual scanning, attention, and processing speed in patients with Parkinson's disease (PD). Lacunes may accelerate the course of PD. Early treatment of vascular disease provides an alternate way to mitigate some motor and cognitive dysfunction in patients with PD.

Predictive Value of Exercise Blood Pressure Changes for Orthostatic Hypotension in Patients With Parkinson's Disease.

BACKGROUND AND PURPOSE: Orthostatic hypotension (OH) is common in patients with Parkinson's disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. METHODS: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET). According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. RESULTS: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649-0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. CONCLUSIONS: This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

Intermittent theta-burst stimulation combined with physical therapy as an optimal rehabilitation in Parkinson's disease: study protocol for a randomised, double-blind, controlled trial.

BACKGROUND: First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson's disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson's disease. METHODS: This randomised, double-blind clinical trial will enrol 50 Parkinson's disease patients aged 45-70 years with Hoehn and Yahr scale scores of 1-3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson's Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate. DISCUSSION: The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson's disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson's disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson's disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022.

Preparation of 3DOM ZrTiO4 Support, WxCeMnOδ/3DOM ZrTiO4 Catalysts, and Their Catalytic Performance for the Simultaneous Removal of Soot and NOx.

As an efficient and durable engine, a diesel engine has a broad application. However, soot particles (PM) and nitrogen oxides (NOx) coming from diesel engines are the main causes of air pollution, so it is necessary to design and prepare an effective catalyst for the simultaneous elimination of PM and NOx. In this work, a novel 3DOM ZrTiO4 support and a series of WxCeMnOδ/3DOM ZrTiO4 catalysts (where x indicates the wt% of W) were designed and fabricated by the colloidal crystal template technique. Among the as-prepared catalysts, the W1CeMnOδ/3DOM ZrTiO4 catalyst exhibits the highest NO conversion rate (52%) at the temperature of maximum CO2 concentration (474°C) and achieves 90% NO conversion in the temperature range of 250-396°C. The excellent catalytic performance is associated with the macroporous structure, abundant oxygen vacancies, sufficient acid sites, and the synergistic effect among the active components. The possible reaction mechanisms of WxCeMnOδ/3DOM ZrTiO4 catalysts were also discussed based on the characterization results.

The quality of life in patients with Parkinson's disease: Focus on gender difference.

BACKGROUND: To improve understanding of gender differences on quality of life (QoL) in patients with Parkinson's disease (PWP) of a different race, the differences of clinical features and health-related quality of life (HRQoL) between male and female PWP were studied in a small cohort early to middle stage of Chinese PWP. METHODS: A cross-sectional study was carried out. PWP were consecutively included from April 2020 to July 2021 in Beijing Rehabilitation Hospital. HRQoL, motor symptoms, and nonmotor symptoms in each patient were evaluated. The differences of demographic, motor symptoms assessments, nonmotor symptoms assessments, and QoL between two gender groups were tested using t-test statistics, Mann-Whitney-Wilcoxon test, or χ2 depending on the data type. To eliminate the possible factors contributing to the QoL, linear regression models were constructed to sort out the effect of gender. RESULTS: One hundred and sixty-two Parkinson's disease (PD) patients were included. Demographic, clinical characteristics, and symptom scale assessments had no statistical differences except for levodopa equivalent daily dose, Hamilton Anxiety Rating Score, REM sleep behavior disorder sleep questionnaire, and Hyposmia Rating Scale score. After baseline imbalance corrections, a significantly higher score of PD Questionnaire-39 (PDQ-39) in female than in male patients(p<.05) was found. In the questionnaire, summary Index and bodily discomfort, stigma, and emotional well-being subscores were the main contribution differences. CONCLUSIONS: Gender differences are associated with the QoL in the early to middle stage PWP in China. Female patients have poorer QoL than male patients, especially bodily discomfort, stigma, and emotional well-being.

Efficacy of C-Mill gait training for improving walking adaptability in early and middle stages of Parkinson's disease.

BACKGROUND: Walking adaptability is an obvious manifestation of Parkinson's disease (PD). Augmented reality technologies such as interactive walkways may improve walking adaptability in patients with Parkinson's Disease (PWP). RESEARCH QUESTION: How effective is C-Mill gait adaptability training in the early and middle stages of PD for improving walking adaptability in motor subtypes of the disease? METHODS: Fifty-two patients with early- or middle-stage PD were divided into two groups according to motor subtype (postural instability/gait disorder [PIGD] and non-PIGD) and received 7 days of training (0.5 h every day, 2 h after medication) on an augmented reality treadmill with built-in visual targets and obstacles. Functional assessments were performed before and after intervention, including posture control and walking, C-gait assessment, and participant experience. The Parkinson Disease Quality of Life questionnaire was administered at 3-month follow-up. RESULTS: Both the PIGD (n = 29) and non-PIGD (n = 23) groups showed improved tandem walking, obstacle avoidance, and overall score in C-gait assessment and Timed Up and Go test after C-Mill training. However, there were no differences between the two groups. The PIGD group showed improvement in visually guided stepping and Speed adaptations, whereas the non-PIGD group did not improve. The non-PIGD group reported they could complete the training with less exertion after the intervention and at the 3-month follow-up, these patients reported improvement in quality of life. SIGNIFICANCE: C-Mill gait adaptation training in the early and middle stages of PD improves walking adaptability in both motor subtypes. Cue strategies are the probable mechanism and may decrease fall risk after training. There was no difference between the groups in the improvements of perceived exertion and quality of life at follow-up. Although PIGD patients showed statistic improvements in visually guided stepping compared with non-PIGD patients, but the difference was not likely to be clinically meaningful. Specific effects of C-mill training for different types of PD were not observed in our study.

Dual-enzyme hydrolysis for preparation of ACE-inhibitory peptides from sesame seed protein: Optimization, separation, and identification.

To prepare and identify ACE-inhibitory peptides originated from sesame seed protein, peptides with strong ACE-inhibitory activities were obtained via the optimization of protease and hydrolysis conditions, and these peptides were purified and identified by membrane separation, gel filtration, and liquid chromatography-mass spectrometry. Results showed that the dual-enzyme comprised alcalase and trypsin with the enzyme activity ratio of 3:7 was suitable to produce ACE-inhibitory peptides. The highest ACE-inhibitory activity of 98.10 ± 0.26% was obtained at the following parameters, pH 8.35, E/S ratio of 6,145 U/g, and hydrolysis time of 4.4 hr. ISGAQPSLR and VVISAPSK ranked the first and second ACE-inhibitory activity among 15 identified ACE-inhibitory peptides. Both peptides influenced ACE via binding with the S1 pocket, S2 pocket, and Zn2+ ion. ISGAQPSLR even impacted the S1' pocket. ISGAQPSLR and VVISAPSK acted as a competitive and noncompetitive inhibitor, respectively. ACE-inhibitory peptides derivated from sesame seed protein have potential applications in functional food. PRACTICAL APPLICATIONS: Although sesame seed protein is proven as the precursor of ACE-inhibitory peptide, preparing ACE-inhibitory peptide from sesame seed protein is still suffering from insufficient information on hydrolysis condition and the peptide sequence. Therefore, the performance of the typical protease on preparing ACE-inhibitory peptide from sesame seed protein has been evaluated, the effect of the amino acid composition of sesame seed protein and cleavage specificity of protease on the generation of ACE-inhibitory peptide has been investigated, hydrolysis conditions have been optimized, the peptide sequence has been identified to illuminate the effect of sesame seed protein fraction on the formation of ACE-inhibitory peptide and discuss the structural characteristics. ACE-inhibitory peptides originating from sesame seed protein could apply in functional food. It is promising for dual-enzyme hydrolysis to utilize in preparation of high-value bioactive peptides.

Enzymatic Preparation and Structure-activity Relationship of Sesaminol.

As a valuable natural antioxidant, sesaminol can be used in food and medicine industries, but it is trace in sesame seeds and oil, and it is feasible to prepare sesaminol from sesaminol triglucoside (STG) which is abundant in defatted sesame cake. Therefore, in order to establish an effective enzymatic preparation method and elucidate the antioxidant structure-activity relationship of sesaminol, a suitable glycosidase for preparing sesaminol from STG were screened, enzymatic hydrolysis was optimized by single-factor test and response surface methodology, and finally, the structure-activity relationship of sesaminol was illustrated by comparative molecular field analysis (CoMFA). These results suggested that ß-galactosidase was the optimal glycosidase for enzymatic hydrolysis of STG to prepare sesaminol. Under the optimal conditions of a reaction temperature of 50°C, reaction time of 4.0 h, pH of 5.5, substrate concentration of 1.0 mg/mL, and enzyme dosage of 20 mg/mL, the conversion rate of sesaminol was 98.88±0.67%. Sesaminol displayed excellent antioxidant ability in 2,2-diphenyl-1-picrylhydrazyl (DPPH, IC50 = 0.0011 mg/mL), 2,2'-azinobis-(3-ethyl-benzothiazoline-6-sulfonate) (ABTS, IC50 = 0.0021 mg/mL) radical scavenging activities and Ferric reducing antioxidant power (FRAP, 103.2998 mol/g) compared to other sesaminol derivatives. According to －log (IC50 of DPPH) and －log (IC50 of ABTS), CoMFA models were successfully established based on Q2 >0.5 (QDPPH 2 = 0.558, QABTS 2 = 0.534). The active site of sesaminol tended to be located on the hydroxyl group of the benzene ring (R1 position). A positive correlation between the bulky and positively charged groups at the 1H, 3H-furo [3, 4-c] furan group, the small, negatively charged groups at the R1 position and the antioxidant activity of sesaminol. This study provides an effective method to prepare sesaminol, reveals the structure-activity relationship of sesaminol and provides theoretical basis to design the novel compound.

Clinical Characteristics, Iron Metabolism and Neuroinflammation: New Insight into Excessive Daytime Sleepiness in Parkinson's Disease.

BACKGROUND: To investigate the clinical characteristics, iron metabolism and neuroinflammation in Parkinson's disease (PD) patients with excessive daytime sleepiness (EDS). METHODS: We studied 379 patients with PD and 30 age-matched controls. All subjects were evaluated by Epworth sleepiness scale (ESS) and a series of rating scales and were divided into PD-EDS and PD-NEDS groups according to ESS score. The concentrations of iron and iron-related proteins and inflammatory cytokines in both cerebrospinal fluid (CSF) and serum were examined. RESULTS: 1. The occurrence rate of EDS in total PD patients was 16.09%. 2. PD-EDS group had significantly severer disease stages, more severe motor and non-motor features of the disease. 3. In CSF, the concentrations of iron and IL-1ß in the PD-EDS group were significantly higher and ferritin concentration was prominently lower when compared with the PD-NEDS group and the control group; ESS score was significantly associated with high concentrations of iron and IL-1ß and low concentration of ferritin in the PD group. Iron concentration was positively correlated with IL-1ß concentration in the PD-EDS group. 4. In serum, no changes were observed in iron and iron-related proteins and inflammatory cytokines among the three groups. CONCLUSION: EDS was a common symptom in PD patients. PD patients with EDS had more severe motor and some non-motor symptoms. Overloaded iron-relevant inflammation in the brain might be an underlying mechanism of PD-EDS.

The Role of the Diaphragm in Postural Stability and Visceral Function in Parkinson's Disease.

Background: In normal subjects, the diaphragm plays a key functional role in postural stability, articulation, respiration, defecation, and urination. Objectives: The aim of this study was to investigate the role of the diaphragm in postural stability and visceral function in patients with Parkinson's disease (PD) and to compare the diaphragm function by gender, Hoehn and Yahr (H&Y) staging, and motor subtypes. Methods: In total, 79 patients were enrolled in this cross-sectional study. The severity of the disease was assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale III and by H&Y staging. Postural stability was quantitatively recorded, and respiratory function was evaluated by spirometry. Several scales were used to evaluate visceral function in patients with PD. In addition, diaphragm ultrasound was used to measure the excursion, contraction velocity, and thickness of the diaphragm during quiet breathing, deep breathing, and the sniff test. Significant features were selected by the least absolute shrinkage and selection operator (LASSO) regression and fitted in the multivariate linear regression and Pearson's correlation analysis. Results: Diaphragm thickness and excursion during quiet breathing were significantly different between men and women and between H&Y stage 1-2 and stage 2.5-3, whereas the diaphragm function was not influenced by motor subtypes. It was shown that the diaphragmatic function was significantly correlated with postural stability, voice function, respiratory function, constipation, and urological function to varying degrees in patients with PD. Conclusion: The diaphragmatic function is associated with dysfunction in PD although it remains unclear as to whether the observed changes in the diaphragm are primary or secondary.