The alleviative effect of Calendula officinalis L. extract against Parkinson's disease-like pathology in zebrafish via the involvement of autophagy activation.

Introduction: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. However, effective preventative or therapeutic agents for PD remain largely limited. Marigold Calendula officinalis L. (CoL) has been reported to possess a wide range of biological activities, but its neuroprotective activity including anti-neurodegenerative diseases is unclear. Here, we aim to investigate whether the extract of CoL (ECoL) has therapeutic activity on PD. Methods: We identified the chemical composition of flavonoid, an important active ingredient in ECoL, by a targeted HPLC-Q-TOF-MS analysis. Subsequently, we evaluated the anti-PD effect of ECoL by using zebrafish PD model induced by 1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine (MPTP). After ECoL+MPTP co-treatments, the changes of dopaminergic neurons, neural vasculature, nervous system, and locomotor activity were examined, respectively. The expressions of genes related to neurodevelopment and autophagy were detected by RT-qPCR. Further, the interaction between autophagy regulators and ECoL flavonoids was predicted using molecular docking method. Results: As a result, 5 kinds of flavonoid were identified in ECoL, consisting of 121 flavones and flavonols, 32 flavanones, 22 isoflavonoids, 11 chalcones and dihydrochalcones, and 17 anthocyanins. ECoL significantly ameliorated the loss of dopaminergic neurons and neural vasculature, restored the injury of nervous system, and remarkably reversed the abnormal expressions of neurodevelopment-related genes. Besides, ECoL notably inhibited the locomotor impairment in MPTP-induced PD-like zebrafish. The underlying anti-PD effect of ECoL may be implicated in activating autophagy, as ECoL significantly upregulated the expressions of genes related to autophagy, which contributes to the degradation of α-synuclein aggregation and dysfunctional mitochondria. Molecular docking simulation showed the stable interaction between autophagy regulators (Pink, Ulk2, Atg7, and Lc3b) and 10 main compounds of flavonoid in ECoL, further affirming the involvement of autophagy activation by ECoL in anti-PD action. Conclusion: Our results suggested that ECoL has the anti-PD effect, and ECoL might be a promising therapeutic candidate for PD treatment.

Climate change risk perception in global: Correlation with petroleum and liver disease: A meta-analysis.

BACKGROUND: Liver diseases have been bound to environmental factors, inclusive of air pollution. The exposure of workers to petrochemicals counts as a possible cause of Liver diseases, whereas results are inconsistent with the previous studies. In this study, a meta-analysis is conducted to assess the pooled risk. METHODS AND FINDING: A systematic search was performed by related researchers. Correlations are analyzed among petroleum and liver cirrhosis mortality, fatty liver, alanine amino transferase (abbreviated as ALT), aspartate amino transferase (abbreviated as AST). Pooled risk ratios (RR) with 95% confidence interval (CI) and effect size(ES) with 95% confidence interval are calculated. Sensitivity analysis and publication bias are also tested. Data are analyzed from 5 studies involving 296 participants. Results are incorporated through adopting a random effects meta-analysis. Working in a petrochemical plant shall not increase the death risk posed by cirrhosis (RR = 0.44, 95% CI [0.36; 0.54]). Yet the incidence of fatty liver increases (RR = 1.22, 95% CI [1.21; 1.23]). Abnormal incidence of ALT and AST also increases. CONCLUSIONS: Occupational exposure plays an important role in causing ALT abnormalities and fatty liver among oil workers, but not a risk factor of cirrhosis, AST abnormalities and liver cancer.

The use of chitosan/PLA nano-fibers by emulsion eletrospinning for periodontal tissue engineering.

OBJECTIVE: In this study, nanofibrous scaffolds base on pure polylactic acid (PLA) and chitosan/PLA blends were fabricated by emulsion eletrospinning. By modulating their mechanical and biological properties, cell-compatible and biodegradable scaffolds were developed for periodontal bone regeneration. METHODS: Pure PLA and different weight ratios of chitosan nano-particle/PLA nano-fibers were fabricated by emulsion eletrospinning. Scanning electron microscope (SEM) was performed to observe the morphology of nano-fibers. Mechanical properties of nano-fibers were tested by single fiber strength tester. Hydrophilic/hydrophobic nature of the nano-fibers was observed by stereomicroscope. In vitro degradation was also tested. Cells were seeded on nano-fibers scaffolds. Changes in cell adhesion, proliferation and osteogenic differentiation were tested by MTT assay and Alizarin Red S staining. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to evaluate the expression of (Toll-like receptor 4) TLR4, IL-6, IL-8, IL-1ß, OPG, RUNX2 mRNA. RESULTS: It is shown that the mean diameter of nano-fibers is about 200 nm. The mean diameter of chitosan nano-particles is about 50 nm. The combination of chitosan nano-particles enhanced the mechanical properties of pure PLA nano-fibers. By adding a certain amount of chitosan nano-particles, it promoted cell adhesion. It also promoted the osteogenic differentiation of bone marrow stem cells (BMSCs) by elevating the expression of osteogenic marker genes such as BSP, Ocn, collagen I, and OPN and enhanced ECM mineralization. Nonetheless, it caused higher expression of inflammatory mediators and TLR4 of human periodontal ligament cells (hPDLCs). CONCLUSION: The combination of chitosan nano-particles enhanced the mechanical properties of pure PLA nano-fibers and increased its hydrophilicity. Pure PLA nano-fibers scaffold facilitated BMSCs proliferation. Adding an appropriate amount of chitosan nano-particles may promote its properties of cell proliferation and osteogenic differentiation. The higher expression of inflammatory mediators caused by nano-fibers may be regulated via TLR4 pathway.

Clinical Efficacy of Acupuncture Treatment in Combination With RehaCom Cognitive Training for Improving Cognitive Function in Stroke: A 2 × 2 Factorial Design Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to identify the clinical efficacy of acupuncture in combination with RehaCom cognitive training in poststroke patients with cognitive dysfunction. METHODS/DESIGN: This study was a 2 × 2 factorial design randomized controlled trial comparing acupuncture, computer-assisted cognitive rehabilitation, and the usual treatment by per-protocol analysis. The trial was completed by 204 stroke patients, including 49 patients in a control group, 52 patients in an acupuncture treatment group, 51 patients in a RehaCom training group, and 52 patients in an acupuncture combined with RehaCom group. All of the patients accepted basic treatment and health education. The interventions continued for 12 weeks (30 minutes per day, 5 days per week). The relative cognitive and functional outcomes were measured at baseline and 12 weeks (at the end of intervention) using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Functional Independence Measure (FIM) scales. RESULTS: After 12 weeks of treatment, the functional statuses of the patients in each of the 4 groups showed varying degrees of improvement. Multiple comparisons of the changes in the MMSE, MoCA, and FIM scores indicated that acupuncture combined with RehaCom cognitive training (ACR) had enhanced therapeutic effects on the functional statuses of the stroke patients (P < .05). In addition, ACR had similar therapeutic effects on the functional statuses of the stroke patients according to each of the assessment scales applied (P△change value MMSE = 0.399, P△MoCA = 0.794, P△FIM = 0.862). The interaction effect values between acupuncture and RehaCom training (acceptance or nonacceptance) were as follows: △MMSE: F = 6.251, P = .013; △MoCA: F = 4.991, P = .027; and △FIM: F = 6.317, P = .013. Further, the main effect values for acupuncture and RehaCom training were both significant (P < .05). CONCLUSIONS: There is an interaction effect in the treatment of stroke patients using ACR. The use of acupuncture in combination with RehaCom training has better therapeutic effects on the functional statuses of poststroke patients than the use of either treatment alone, demonstrating the clinical significance of this combination therapy.

Effects of acupuncture and computer-assisted cognitive training for post-stroke attention deficits: study protocol for a randomized controlled trial.

BACKGROUND: A majority of stroke survivors present with cognitive impairments. Attention disturbance, which leads to impaired concentration and overall reduced cognitive functions, is strongly associated with stroke. The clinical efficacy of acupuncture with Baihui (GV20) and Shenting (GV24) as well as computer-assisted cognitive training in stroke and post-stroke cognitive impairment have both been demonstrated in previous studies. To date, no systematic comparison of these exists and the potential beneficial effects of a combined application are yet to be examined. The main objective of this pilot study is to evaluate the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The second objective is to test the effects of a combined cognitive intervention that incorporates computer-assisted cognitive training and acupuncture (ACoTrain). METHODS/DESIGN: An international multicentre, single-blinded, randomised controlled pilot trial will be conducted. In a 1:1:1 ratio, 60 inpatients with post-stroke cognitive dysfunction will be randomly allocated into either the acupuncture group, the computer-assisted cognitive training group, or the ACoTrain group in addition to their individual rehabilitation programme. The intervention period of this pilot trial will last 4 weeks (30 minutes per day, 5 days per week, Monday to Friday). The primary outcome is the test battery for attentional performance. The secondary outcomes include the Trail Making Test, Test des Deux Barrages, National Institute of Health Stroke Scale, and Modified Barthel Index for assessment of daily life competence, and the EuroQol Questionnaire for health-related quality of life. DISCUSSION: This trial mainly focuses on evaluating the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The results of this pilot trial are expected to provide new insights on how Eastern and Western medicine can complement one another and improve the treatment of cognitive impairments in early stroke rehabilitation. Including patients with different cultural backgrounds allows a more generalisable interpretation of the results but also poses risks of performance bias. Using standardised and well-described assessments, validated for each region, is pivotal to allow pooling of the data. TRIAL REGISTRATION: Clinical Trails.gov ID: NCT02324959 (8 December 2014).

Effect of integrated cognitive therapy on hippocampal functional connectivity patterns in stroke patients with cognitive dysfunction: a resting-state FMRI study.

Objective. This study aimed to identify abnormal hippocampal functional connectivity (FC) following ischemic stroke using resting-state fMRI. We also explored whether abnormal hippocampal FC could be modulated by integrated cognitive therapy and tested whether these alterations were associated with cognitive performance. Methods. 18 right-handed cognitively impaired ischemic stroke patients and 18 healty control (HC) subjects were included in this study. Stroke subjects were scanned at baseline and after integrated cognitive therapy, while HCs were only scanned at baseline, to identify regions that show significant correlations with the seed region. Behavioral and cognitive assessments were obtained before each scan. Results. During the resting state, we found abnormal hippocampal FC associated with temporal regions, insular cortex, cerebellum, and prefrontal cortex in stroke patients compared to HCs. After integrated cognitive therapy, however, the stroke group showed increased hippocampal FC mainly located in the prefrontal gyrus and the default mode network (DMN). Altered hippocampal FC was associated with cognitive improvement. Conclusion. Resting-state fMRI may provide novel insight into the study of functional networks in the brain after stroke. Furthermore, altered hippocampal FC may be a compensatory mechanism for cognitive recovery after ischemic stroke.

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

BACKGROUND: Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. METHOD/DESIGN: A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. DISCUSSION: The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.