Gastric-filling ultrasonography to evaluate gastric motility in patients with Parkinson's disease.

Background: Delayed gastric emptying is a common non-motor symptom of Parkinson's disease (PD). However, there is currently no objective evaluation and diagnostic method for this condition. Objectives: The purpose of this study was to evaluate the feasibility of gastric-filling ultrasonography for gastric motility in patients with PD and the relationship between gastric dynamics and gastrointestinal symptoms and motor symptoms of PD. Design setting and patients: We performed a case-control study with 38 patients with PD and 34 healthy controls. Methods: All patients underwent a 120-min ultrasonography examination using a 500-ml semi-liquid test meal. We determined the antral contraction amplitude (ACA), the antrum contraction frequency (ACF), the motility index (MI), and the gastric antral cross-sectional area (CSA). We acquired the CSA at six time points: fasting for 12 h (T0), immediately after drinking the semi-liquid test meal (T1); and at 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min. We calculated the gastric emptying rate (GER) at different time points by using the CSA. We compared the GER between the groups and evaluated the correlation between the GER and gastrointestinal symptoms and motor symptoms of PD. Results: The MI and ACF were significantly lower in the PD group compared with the control group (P < 0.05). The GER at T30 and the ACA showed no significant difference between the groups (P > 0.05). At different time points, the GER was significantly different between the PD and control groups (P < 0.001). There was no significant association between the GER and gastrointestinal symptoms; none of them were risk factors for impaired gastric emptying (odds ratio > 1). The GER was negatively correlated with the severity of PD motor symptoms (P < 0.05). Conclusion: Patients with PD had significantly delayed gastric emptying, which was negatively correlated with the severity of PD motor symptoms. Measuring gastric emptying by gastric-filling ultrasound had good diagnostic value in clinical screening for delayed gastric motility in patients with PD. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=126304.

Facial muscle movements in patients with Parkinson's disease undergoing phonation tests.

Purpose: Parkinson's disease (PD) is a serious neurodegenerative disease affecting the elderly. In general, the locomotion deficit, which seriously affects the daily life of patients with PD, usually occurs at a later stage. The mask face symptom meanwhile progressively worsens. However, facial muscle disorders and changes involved in the freezing mask are unclear. Method: In this study, we recruited 35 patients with PD and 26 age- and sex-balanced controls to undergo phonation tests, while the built-in camera on the laptop recorded their facial expressions during the whole pronunciation process. Furthermore, FaceReader (version 7.0; Noldus Information Technology, Wageningen, Netherlands) was used to analyze changes in PD facial landmark movement and region movement. Results: The two-tailed Student's t-test showed that the changes in facial landmark movement among 49 landmarks were significantly lower in patients with PD than in the control group (P < 0.05). The data on facial region movement revealed that the eyes and upper lip of patients with PD differed significantly from those in the control group. Conclusion: Patients with PD had defects in facial landmark movement and regional movement when producing a single syllable, double syllable, and multiple syllables, which may be related to reduced facial expressions in patients with PD.

Correlation between head tremble and the severity of Parkinson's disease.

INTRODUCTION: Parkinson's (PD) is a common degenerative disease of the central nervous system. It affects more than 6 million individuals worldwide. The typical clinical manifestations include static tremor, slow movement, and unstable posture. However, the correlation between head tremor and the severity of PD remains unclear. METHODS: In the current study, 18 patients and 18 healthy subjects were recruited to undergo a phonation test. Noldus facereader 7.0 software was used to analyze the range of head trembling between the two groups. RESULTS: The data revealed that patients with PD had significant differences in the x-, y-, and z-axis of head movement with respect to the specific pronunciation syllables compared with the normal group. Moreover, the head movement of the patients with PD was positively correlated with the severity of the disease in the single, double, and multiple syllable tests. In the phonetic test, the head displacement of patients with PD was significantly greater than that of healthy individuals, and the displacement range was positively correlated with the severity of the disease. CONCLUSION: These pieces of evidence suggested that the measurement of head displacement assists the early diagnosis and severity of the disease.

Extraction and separation of flavonoids from Malus hupehensis using high-speed countercurrent chromatography based on deep eutectic solvent.

In the present experiment, a green and highly efficient extraction method for flavonoids established on deep eutectic solvents (DESs) was investigated by using the response surface methodology. The DES-based high-speed countercurrent chromatography (HSCCC) solvent systems were developed for the separation of high purity compounds from the DES extract of Malus hupehensis for the first time. Under the optimal conditions (liquid-to-solid ratio of 26.3 mL/g, water content of 25.5%, and extraction temperature of 77.5°C), the yield of flavonoids was 15.3 ± 0.1%, which was superior to that of the methanol extraction method. In accordance with the physical property of DES-based HSCCC solvent systems and K values of target compounds, DES-based HSCCC solvent systems composed of choline chloride/glucose-water-ethyl acetate (ChCl/Glu-H2O-EAC, 1:1:2, v/v) was selected for the HSCCC separation. Thus, five flavonoids (two novel compounds 1-2, 6´´-O-coumaroyl-2´-O-glucopyranosylphloretin and 3´´´-methoxy-6´´-O-feruloy-2´-O-glucopyranosylphloretin; three know compounds 3-5, namely, avicularin, phloridzin, and sieboldin) were efficiently separated from Malus hupehensis. DESs are the environment friendly and highly efficient solvents as the components of extraction solvent and HSCCC solvent system, and can be re-utilized many times. However, ethyl acetate can be soluble with a few hydrogen bond donors, such as urea, carboxylic acid and polyol, through the shake flask test. It is the great difficulty for the efficient and rapid separation of target compounds from the DESs extract because of the DESs residual in the HSCCC fractions. ChCl and Glu are the great choices of DESs without this problem. In addition, K values increased with the increase of the molar ratio of ChCl/Glu and the content of water, which could effectively guide us to choose the suitable DES-based HSCCC solvent system. The twice HSCCC separation results indicated that DES was the valuable and green solvent for the HSCCC separation of pure compounds from the extract for the first time, and showed the recycle superiority of DES-based HSCCC solvent system.

Separation of six antioxidants from Hypsizygus marmoreus by high-speed countercurrent chromatography utilizing an approach based upon the polarity parameter model.

For a successful high-speed countercurrent chromatography (HSCCC) separation of multiple components, the suitable solvent system selection is a critical operation. Despite the difference in separation mechanism between HSCCC and HPLC, K values of compounds in the solvent system and the retention factor of compounds in HPLC were connected with polarity, and the polarity mainly depended on the structure and chemical properties of compounds. On the basis of the concept of "like dissolves like", the average polarity of the solvent system is equal to the average polarity of multiple components at the "sweet point" log K = 0. The result of theoretical deduction showed a negative linear correlation between the polarity of each component and the logarithm of the gradient range of the organic phase. Therefore, the average polarity of unknown multiple components could be obtained through the polarity parameter model established in the HPLC analysis. The suitable solvent system composed of n-hexane-ethyl acetate-methanol-water (8:3:8:1, v/v) was selected through the average polarity of multi-components combining K values of the enriched samples. In the context of bioassay, an efficient HSCCC separation procedure was established, and two groups of analogue benzaldehyde derivatives (four main antioxidants, namely, isodihydroauroglaucin, isoaspergin, isotetrahydro-auroglaucin, and flavoglaucin; two minor antioxidants, namely, 6'-oxo-chaetopyranin and chaetopyranin) were obtained from Hypsizygus marmoreus. The predicted polarity values of multi-components were sufficient to meet the HSCCC experimental requirements. The HPLC analysis of reference compounds and multi-components showed a significant consistency with different chromatographic columns. Therefore, the polarity parameter model established in the HPLC analysis was a simple, rapid, and helpful tool for looking an appropriate solvent system, which was a forwarding step for the HSCCC separation of multiple components.

The physical significance of acoustic parameters and its clinical significance of dysarthria in Parkinson's disease.

Dysarthria is universal in Parkinson's disease (PD) during disease progression; however, the quality of vocalization changes is often ignored. Furthermore, the role of changes in the acoustic parameters of phonation in PD patients remains unclear. We recruited 35 PD patients and 26 healthy controls to perform single, double, and multiple syllable tests. A logistic regression was performed to differentiate between protective and risk factors among the acoustic parameters. The results indicated that the mean f0, max f0, min f0, jitter, duration of speech and median intensity of speaking for the PD patients were significantly different from those of the healthy controls. These results reveal some promising indicators of dysarthric symptoms consisting of acoustic parameters, and they strengthen our understanding about the significance of changes in phonation by PD patients, which may accelerate the discovery of novel PD biomarkers.

Dichloromethane Extract of Fermentation Broth by Co-Culture of Morchella esculenta and Coprinus comatus Induces Apoptosis in U251 Cells via Mitochondrial Intrinsic Pathway.

The current study was designed to investigate the inhibitory effects of dichloromethane extract of fermentation broth by co-culture of Morchella esculenta and Coprinus comatus (DCMM) on human glioma U251 cells in vitro and its possible underlying mechanisms. The proliferation of U251 cells was inhibited by DCMM with different concentrations by the CCK-8 assay. Besides, flow cytometry assay was used to evaluate the DCMM promoted U251 cell apoptosis rate in a dose-dependent manner. DCMM with different concentrations (10 µg·mL-1, 20 µg·mL-1, and 40 µg·mL-1) significantly enhanced the expression of caspases-3 activity after 24 h. In addition, DCMM with different concentrations significantly increased caspase-3 and Bax, and decreased Bcl-2 expressions at both mRNA and protein levels. DCMM can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to induction of apoptosis of human glioma U251 cells by mitochondrial intrinsic pathway.

An efficient high-speed countercurrent chromatography method for preparative separation of javanicin from Fusarium solani, a fungus isolated from the fruiting body of the mushroom Trametes trogii.

To develop an efficient method for large preparation of javanicin from Fusarium solani, a rapid and simple method by high-speed countercurrent chromatography was established based on average polarity (P' values) and partition coefficients (K values) of crude samples. A suitable solvent system for high-speed countercurrent chromatography was selected from many possible biphasic solvent systems. HSCCC was successfully applied to separate and purify javanicin, the main bioactive component of solid cultures of the fungus F. solani isolated from the fruiting body of Trametes trogii, with petroleum ether-ethyl acetate-methanol-water (4:3:2:1, v/v) as solvent system. A total amount of 40.6 mg of javanicin was obtained from 100 mg crude sample. The purity of javanicin was 92.2% with a recovery of 95.1%, as determined by high-performance liquid chromatrography. The molecular structure was identified primarily by NMR and MS methods. The results indicated that high-speed countercurrent chromatography could be a powerful technology for separating naphthoquinones from the solid cultures of the fungus F. solani. It is also of significance that the separation of javanicin from natural source was carried out for the first time utilizing high-speed countercurrent chromatography.

Asperpyrone F, a new dimeric naphtho-γ-pyrone from the edible fungus Pleurotus ostreatus.

A new dimeric naphtho-γ-pyrone, asperpyrone F (1), along with six known ones, asperpyrones B (2) and C (3), fonsecinones A (4) and B (5), aurasperones A (6) and E (7), have been isolated from the solid culture of the edible fungus Pleurotus ostreatus. The structures of 1-7 were determined mainly by NMR and MS experiments. The absolute configuration of compound 1 was assigned via the circular dichroism (CD) data analysis. Compounds 1-7 showed modest antioxidant and immunomodulatory activities. All compounds were isolated from the fungus P. ostreatus for the first time.

Separation of five naphtho-γ-pyrones from Pleurotus ostreatus by high-speed countercurrent chromatography.

A method to optimize a high-speed countercurrent chromatography solvent system from many possible solvent systems was guided by average polarity and K values of crude samples, which was successfully applied in separation of the naphtho-γ-pyrones. This method expanded the scope of spectrophotometer application in the solvent systems selection, and showed the merits of simplicity, rapidity, and low reagent consumption. As a consequence of utilizing the method, an efficient separation procedure was established, and two groups of naphtho-γ-pyrone isomers (fonsecinone B and asperpyrone F; asperpyrone C, fonsecinone A, and aurasperone A) were obtained from Pleurotus ostreatus by high-speed countercurrent chromatography with a solvent system composed of petroleum ether/ethyl acetate/methanol/water (5:5:5:5, v/v). The results indicate that high-speed countercurrent chromatography could be a powerful technology for separation isomers and analogues, and the method guided by average polarity and K values of crude samples is feasible to optimize solvent system.

Total flavones of fermentation broth by co-culture of Coprinus comatus and Morchella esculenta induces an anti-inflammatory effect on LPS-stimulated RAW264.7 macrophages cells via the MAPK signaling pathway.

The inflammatory cellular model of RAW264.7 cells induced by lipopolysaccharide (LPS) has always been used to investigate the effect of anti-inflammatory agents in vitro. In the present study, the anti-inflammatory activity of total flavones extracted from the fermentation broth of the co-culture of Coprinus comatus and Morchella esculenta (MCF-F), and its potential molecular mechanism in LPS-challenged RAW264.7 macrophage cells were investigated. The data revealed that MCF-F exhibited anti-inflammatory activity in LPS-stimulated RAW264.7 cells. At the same time, MCF-F was less cytotoxic under a concentration of 16 µg/ml in RAW264.7 cells. The anti-inflammatory activity of MCF-F was detected using the Griess method and ELISA assay, and the results well-corroborated with the observed decrease in expression in pro-inflammatory mediators, including nitric oxide, tumor necrosis factor-α and inteleukin-1ß (IL-1ß). In addition, the expression of inducible NO synthase (iNOS) and cyclooxygenase2 (COX-2) were confirmed by RT-PCR and western blot, and it was found that both mRNA and protein levels were downregulated after MCF-F treatment. The data also revealed that MCF-F downregulated the phosphorylation of JNK, ERK and P38 MAPK. Collectively, these results lead to the conclusion that MCF-F exerts an anti-inflammatory effect against LPS-challenged RAW264.7 cells via the MAPK pathway.

A new prenylated indole diketopiperazine alkaloid from Eurotium cristatum.

A new prenylated indole diketopiperazine alkaloid, cristatumin F (1), and four known metabolites, echinulin (2), dehydroechinulin (3), neoechinulin A (4) and variecolorin O (5), were isolated from the crude extract of the fungus Eurotium cristatum. The structure of 1 was elucidated primarily by NMR and MS methods. The absolute configuration of 1 was assigned using Marfey's method applied to its acid hydrolyzate. Cristatumin F (1) showed modest radical scavenging activity against DPPH radicals, and exhibited marginal attenuation of 3T3L1 pre-adipocytes.

Two new imidazolone-containing alkaloids and further metabolites from the ascomycete fungus Tricladium sp.

Tricladins A and B (1 and 2, resp.), new imidazolone-containing alkaloids, together with five known metabolites, bacillamides A, B (3 and 4, resp.), 20-hydroxyaflavinine (5), N-(2-phenylethyl)acetamide (6), and N(b)-acetyltryptamine (7), have been isolated from the crude extract of the ascomycete fungus Tricladium sp. The structures of 1 and 2 were elucidated primarily by NMR and MS methods. Compound 2 showed marginal cytotoxicity against MDA-MB-231 human breast cancer cells, whereas the known metabolite 4 displayed an inhibitory effect on HIV-1 replication in C8166 cells.

Verrucamides A-D, antibacterial cyclopeptides from Myrothecium verrucaria.

Four new cyclic tetradecapeptides, verrucamides A-D (1-4), have been isolated from the solid-substrate fermentation culture of the ascomycete fungus Myrothecium verrucaria. The structures of these compounds, each featuring six N-methylated amino acid residues, were elucidated primarily by NMR and MS methods. The absolute configurations of 1-4 were assigned by application of Marfey's method on their acid hydrolysates. Compounds 1-4 showed antimicrobial activity against the Gram-positive bacterium Staphylococcus aureus.