The effect of electroacupuncture at ST25 on Parkinson's disease constipation through regulation of autophagy in the enteric nervous system.

The effectiveness and safety of electroacupuncture (EA) for constipation have been confirmed by numerous clinical studies and experiments, and there are also studies on the efficacy of EA for Parkinson's disease (PD) motor symptoms. However, there are few researches on EA for PD constipation. Autophagy is thought to be involved in the mechanistic process of EA in the central nervous system (CNS) intervention in Parkinson's pathology. However, whether it has the same effect on the enteric nervous system (ENS) has not been elucidated. Therefore, we investigated whether EA at Tianshu (ST25) acupoint promotes the clearance of α-Syn and damaged mitochondria aggregated in the ENS in a model of rotenone-induced PD constipation. This study evaluated constipation symptoms by stool characteristics, excretion volume, and water content, and the expression levels of colonic ATG5, LC3II, and Parkin were detected by Western Blot (WB) and Real-Time Quantitative PCR (RT-qPCR). The relationship between the location of α-Syn and Parkin in the colonic ENS was observed by immunofluorescence (IF). The results showed that EA intervention significantly relieved the symptoms of rotenone-induced constipation in PD rats, reversed the rotenone-induced down-regulation of colonic ATG5, LC3II, and Parkin expression, and the positional relationship between colonic α-Syn and Parkin proved to be highly correlated. It is suggested that EA might be helpful in treating PD constipation by modulating Parkin-induced mitochondrial autophagy.

Parkinson's disease constipation effect of electroacupuncture at ST25 through colonic motility and enteric neuropathology.

Background: The enteric nervous system (ENS) plays a central role in developing Parkinson's disease (PD) constipation, and the regulation of the ENS may be a key component in treating PD constipation. Electroacupuncture (EA) can effectively treat constipation symptoms in PD, but research on its specific mechanisms, especially in terms of ENS, is relatively lacking. Therefore, we investigated whether EA at ST25 promotes the restoration of ENS structure and colonic motor function in the rotenone-induced PD constipation rat model. Methods: In this study, we evaluated constipation symptoms by stool characteristics, excretion and water volume, and whole gut transit time and observed colonic motility regulation through colonic motion detection and pathological changes in the colonic myenteric nervous plexus by transmission electron microscopy and immunofluorescence staining. Results: EA significantly improved the constipation symptoms and positively adjusted the colonic motility in rotenone-induced PD constipation rats. At the same time, EA reversed the rotenone-induced colonic myenteric nervous plexus injury and regulated the ratio of inhibitory and excitatory neurotransmitters. Conclusion: Our results indicate that EA treatment of PD constipation may be mediated through the adjustment of ENS.

CD73 regulates hepatic stellate cells activation and proliferation through Wnt/ß-catenin signaling pathway.

Alcoholic liver fibrosis (ALF) is commonly associated with long-term alcohol consumption and the activation of hepatic stellate cells (HSCs). Inhibiting the activation and proliferation of HSCs is a critical step to alleviate liver fibrosis. Increasing evidence indicates that ecto-5'-nucleotidase (CD73) plays a vital role in liver disease as a critical component of extracellular adenosine pathway. However, the regulatory role of CD73 in ALF has not been elucidated. In this study, both ethanol plus CCl4-induced liver fibrosis mice model and acetaldehyde-activated HSC-T6 cell model were employed and the expression of CD73 was consistently elevated in vivo and in vitro. C57BL/6 J mice were intraperitoneally injected with CD73 inhibitor Adenosine 5'-(α, ß-methylene) diphosphate sodium salt (APCP) from 5th week to the 8th week in the development of ALF. The results showed APCP could inhibit the activation of HSCs, reduce fibrogenesis marker expression and thus alleviate ALF. Silencing of CD73 inhibited the activation of HSC-T6 cells and promoted apoptosis of activated HSC-T6 cells. What's more, the proliferation of HSC-T6 cells was inhibited, which was characterized by decreased cell viability and cycle arrest. Mechanistically, Wnt/ß-catenin pathway was activated in acetaldehyde-activated HSC-T6 cells and CD73 silencing or overexpression could regulate Wnt/ß-catenin signaling pathway. Collectively, our study unveils the role of CD73 in HSCs activation, and Wnt/ß-catenin signaling pathway might be involved in this progression.

Diagnostic efficacy of 2-shot compressed sensing cine sequence cardiovascular magnetic resonance imaging for left ventricular function.

BACKGROUND: Cardiac magnetic resonance cine images are conventionally acquired in breath-hold with a segmented balanced steady-state free precession (bSSFP) sequence, which requires a relatively long acquisition time and high patient cooperation. The single-shot compressed sensing (ss CS) cine sequence is a real-time sequence that has reasonable spatial and temporal resolution and can be applied during free breathing. However, the contrast between the myocardium and surrounding soft tissue is relatively reduced, and the epicardial delineation results are not as accurate with the ss CS cine sequence compared with the bSSFP sequence. In this study, we evaluated the use of a 2-shot CS cine technique in quickly acquiring high-quality images and accurately assessing cardiac function in clinical practice. METHODS: The patients enrolled in the study underwent cardiovascular magnetic resonance (CMR) on a 3T scanner from Jul. to Dec. 2018. Cine imaging was performed with 3 different methods: a standard segment cine sequence, a real-time ss CS cine sequence, and a 2-shot CS cine sequence prototype. Quantitative analysis of image quality was performed using a 0-4 scoring system, and also edge sharpness was measured, and cardiac function analysis was performed for all 3 types of cine images. RESULTS: Thirty-eight patients underwent imaging with the three types of cine sequences. The average scan time of the standard cine sequence was 101±20 s, the average scan time of the ss CS cine sequence was 20±4 s, and the average scan time of the 2-shot CS cine sequence was 30±6 s. The standard cine sequence image score was 3.68±0.64 and edge sharpness was (2.47±0.18) mm, the ss CS cine sequence image score was 3.13±0.35 and edge sharpness was (4.69±0.02) mm, and the 2-shot cine sequence image score was 3.54±0.51 and the edge sharpness was (2.51±0.13) mm. In terms of the quantitative study of cardiac function, the differences between the standard cine sequence and the ss CS cine sequence were not statistically significant, except for those of the imaging score and LV mass. There were no significant differences in the cardiac function parameters between the standard cine sequence and the 2-shot cine sequence. There was a strong correlation between the standard cine and ss CS cine sequences and between the standard cine and 2-shot CS cine sequences (P<0.01) of all the cardiac function parameters. CONCLUSIONS: The 2-shot CS cine sequence can acquire images with a level of quality comparable to that of the standard cine sequence in a significantly shorter period of time. The functional parameters are similar between the 2-shot CS cine sequence and the standard cine sequence.

[Feasibility of Non-contrast-enhanced Coronary Magnetic Resonance Angiography at 3.0T].

Objective To evaluate the feasibility of non-contrast-enhanced magnetic resonance angiography (NCE-MRA) on a 3.0T scanner. Methods Totally 36 volunteers and 24 patients with clinically suspected coronary artery disease underwent NCE-MRA. The quality of the NCE-MRA images was graded for each segment on a four-point scale. The subjects were divided into two groups according to image quality. The age,body mass index (BMI),heart rate,end-expiratory diaphragm displacement,and respiratory diaphragm motion amplitude were evaluated and compared. Results The average image quality score of every segment was above 2 points. The proximal and middle segments of left anterior descending artery had significantly higher quality scores than the distal segments (P=0.000) and the proximal segment of left circumflex coronary artery had significantly higher quality scores than the distal segments (P=0.000),the proximal segment of right coronary artery also had a significant higher quality score than its distal segment (P=0.001). The image quality was good in 38 subjects (64.4%). The heart rate [(66.35±9.39) beat/min vs. (75.32±11.67) beat/min] (P=0.002) and the body mass index [(24.72±3.33) kg/m 2 vs. (27.82±3.61) kg/m 2] (P=0.002) were significantly different between the good image quality group and the poor image quality group. The end-expiratory diaphragm displacement in good image quality group was (4.43±2.07)mm,which was significantly lower than that in poor image quality group [(9.26±7.62)mm](P=0.013). The respiratory diaphragm motion amplitude [(21.35±6.02) mm] in good image quality group was significantly lower than that in poor image quality group [(30.68±14.20)mm](P=0.012). Conclusion NCE-MRA on 3.0T is a feasible tool for visualization of the proximal and middle segments of coronary arteries,and the image quality can be optimized by controlling heart rate and respiration in the future.

Regulation of CD39 expression in ATP-P2Y2R-mediated alcoholic liver steatosis and inflammation.

Inflammation plays a central role in the progression of alcoholic liver disease. ATP-P2Y2R signaling and CD39 play an important role in various diseases, but little is known about their role in alcoholic liver steatosis and inflammation. As a transmembrane hydrolase, CD39 hydrolyzes ATP, while the mutual regulation of CD39 and ATP-P2Y2R in alcoholic steatohepatitis is poorly understood. Here, we found that the expression of ATP, P2Y2R, and CD39 is increased significantly both in the liver of alcohol-fed mice and alcohol-induced RAW264.7 cell lines. In this study, C57BL/6 mice were intrapretationally injected with P2Y2R inhibitor suramin from day 4 until day 10 during the induction of a chronic/binge drinking model. Pharmacological blockade of P2Y2R largely prevents liver damage, lipid accumulation, and inflammation, with concomitant down-expression of CD39 in liver. We found that the inhibition of P2Y2R in vitro reduces inflammation via down-expression of interleukin 6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α), and the expression of CD39 was reduced, whereas the activation of P2Y2R showed an opposite effect. Silencing of CD39 promoted the expression of ATP and P2Y2R. These results indicate that CD39 attenuates alcohol-induced steatohepatitis by scavenging extracellular ATP to indirectly regulate the expression of P2Y2R. Interestingly, P2Y2R paradoxically boosts CD39 activity. Thus, blockade of the extracellular ATP-P2Y2R signalling represents a potential therapeutic approach against alcoholic liver disease, and CD39 is a potential therapeutic target.

High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH.

The development and/or progression of perihematomal edema (PHE) in patients with acute spontaneous intracerebral hemorrhage (ICH) vary substantially with different individuals. Although hematoma volume is a useful indicator for predicting PHE, its predictive power was not good at the early stage of ICH. Better predictors are urgently needed. In this study, we found that miR-130a was elevated in the serum of ICH patients and was an independent indicator positively associated with PHE volume within the first 3 days after onset. The R (2) was further evaluated when it is used in combination with hematoma mass. Serum miR-130a levels were associated with clinical outcome (National Institute of Health Stroke Scale (NIHSS) scores at day 14 and modified Rankin Scale (mRS) scores at day 90) only in patients with deep hematoma. Moreover, miR-130a was significantly increased in rat serum and perihematomal tissues and was in line with the change in brain edema. MiR-130a inhibitors reduced brain edema, blood-brain barrier (BBB) permeability, and increased neurological deficit scores, and miR-130a mimics increased monolayer permeability. Thrombin-stimulated brain microvascular endothelial cells (BMECs) were a main source of miR-130a under ICH. In the experimental model, the elevated miR-130a level was accompanied by the decreased caveolin-1 and increased matrix metalloproleinase (MMP)-2/9. Meanwhile, caveolin-1 (cav-1) was reduced by miR-130a mimics, accompanied by an increase in MMP-2/9 expression. The upregulated MMP-2/9 was then downregulated by cavtratin, a cav-1 scaffolding domain peptide. This regulation mechanism was authenticated in a thrombin-induced cellular ICH model. Our results suggest that serum miR-130a may serve as a useful early biomarker for monitoring post-ICH PHE and predicting prognosis and may be helpful in the decision-making of individualized therapy.