Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study.

Objective: Motor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke. Methods: In this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl-Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects. Results: Through machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups. Conclusion: Feature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

Altered Effective Connectivity of Resting-State Networks by Tai Chi Chuan in Chronic Fatigue Syndrome Patients: A Multivariate Granger Causality Study.

Numerous evidence has shown that patients with chronic fatigue syndrome (CFS) have changes in resting brain functional connectivity, but there is no study on the brain network effect of Tai Chi Chuan intervention in CFS. To explore the influence of Tai Chi Chuan exercise on the causal relationship between brain functional networks in patients with CFS, 21 patients with CFS and 19 healthy controls were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning and 36-item Short-Form Health Survey (SF-36) scale assessment before and after 1month-long training in Tai Chi Chuan. We extracted the resting brain networks using the independent component analysis (ICA) method, analyzed the changes of FC in these networks, conducted Granger causality analysis (GCA) on it, and analyzed the correlation between the difference causality value and the SF-36 scale. Compared to the healthy control group, the SF-36 scale scores of patients with CFS were lower at baseline. Meanwhile, the causal relationship between sensorimotor network (SMN) and default mode network (DMN) was weakened. The above abnormalities could be improved by Tai Chi Chuan training for 1 month. In addition, the correlation analyses showed that the causal relationship between SMN and DMN was positively correlated with the scores of Role Physical (RP) and Bodily Pain (BP) in CFS patients, and the change of causal relationship between SMN and DMN before and after training was positively correlated with the change of BP score. The findings suggest that Tai Chi Chuan is helpful to improve the quality of life for patients with CFS. The change of Granger causality between SMN and DMN may be a readout parameter of CFS. Tai Chi Chuan may promote the functional plasticity of brain networks in patients with CFS by regulating the information transmission between them.

The heart-brain axis: A proteomics study of meditation on the cardiovascular system of Tibetan Monks.

BACKGROUND: There have been mixed reports on the beneficial effects of meditation in cardiovascular disease (CVD), which is widely considered the leading cause of death worldwide. METHODS: To clarify the role of meditation in modulating the heart-brain axis, we implemented an extreme phenotype strategy, i.e., Tibetan monks (BMI > 30) who practised 19.20 ± 7.82 years of meditation on average and their strictly matched non-meditative Tibetan controls. Hypothesis-free advanced proteomics strategies (Data Independent Acquisition and Targeted Parallel Reaction Monitoring) were jointly applied to systematically investigate and target the plasma proteome underlying meditation. Total cholesterol, low-density lipoprotein cholesterol  (LDL-C), apolipoprotein B (Apo B) and lipoprotein (a) [Lp(a)] as the potential cardiovascular risk factors were evaluated. Heart rate variability (HRV) was assessed by electrocardiogram. FINDINGS: Obesity, hypertension, and reduced HRV is offset by long-term meditation. Notably, meditative monks have blood pressure and HRV comparable to their matched Tibetan controls. Meditative monks have a protective plasma proteome, related to decreased atherosclerosis, enhanced glycolysis, and oxygen release, that confers resilience to the development of CVD. In addition, clinical risk factors in plasma were significantly decreased in monks compared with controls, including total cholesterol, LDL-C, Apo B, and Lp(a). INTERPRETATION: To our knowledge, this work is the first well-controlled proteomics investigation of long-term meditation, which opens up a window for individuals characterized by a sedentary lifestyle to improve their cardiovascular health with an accessible method practised for more than two millennia. FUNDING: See the Acknowledgements section.

Progressive increase of high-frequency EEG oscillations during meditation is associated with its trait effects on heart rate and proteomics: a study on the Tibetan Buddhist.

Meditation has been a spiritual and healing practice in the East for thousands of years. However, the neurophysiologic mechanisms underlying its traditional form remain unclear. In this study, we recruited a large sample of monks (n = 73) who practice Tibetan Buddhist meditation and compared with meditation-naive local controls (n = 30). Their electroencephalography (EEG) and electrocardiogram signals were simultaneously recorded and blood samples were collected to investigate the integrative effects of Tibetan Buddhist on brain, heart, and proteomics. We found that the EEG activities in monks shifted to a higher frequency from resting to meditation. Meditation starts with decrease of the (pre)frontal delta activity and increase of the (pre)frontal high beta and gamma activity; while at the deep meditative state, the posterior high-frequency activity was also increased, and could be specified as a biomarker for the deep meditation. The state increase of posterior high-frequency EEG activity was significantly correlated with the trait effects on heart rate and nueropilin-1 in monks, with the source of brain-heart correlation mainly locating in the attention and emotion networks. Our study revealed that the effects of Tibetan Buddhist meditation on brain, heart, and proteomics were highly correlated, demonstrating meditation as an integrative body-mind training.

[Antioxidant mechanism of gastrodin combined with isorhynchophylline in inhibiting MPP~+-induced apoptosis of PC12 cells].

Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis is the most frequently used herbal pair in the treatment of Parkinson's disease(PD). Gastrodin and isorhynchophylline are important components of Gastrodiae Rhizoma-Uncariae Ramulus cum Uncis herb pair with anti-Parkinson mechanism. This study aimed to investigate the effect of gastrodin combined with isorhynchophylline on 1-methyl-4-phenylpyridinium(MPP~+)-induced apoptosis of PC12 cells and their antioxidant mechanism. The leakage of lactate dehydrogenase(LDH) from cells to media was analyzed by spectrophotometry. Apoptotic cells were labeled with Annexin V-fluorescein isothiocyanate(FITC) and propidium iodide(PI) and analyzed by flow cytometry. The cell cycle was analyzed using propidium iodide(PI) staining. Lipid peroxidation(LPO) level was analyzed by spectrophotometry. The mRNA expression of caspase-3 was examined by Real-time RT-PCR. The protein expressions of heme oxygenase 1(HO-1) and NADPH: quinoneoxidore-ductase 1(NQO-1) were determined by Western blot. Gastrodin combined with isorhynchophylline reduced the percentage of Annexin V-positive cells and cell cycle arrest in MPP~+-induced PC12 cells. Gastrodin combined with isorhynchophylline down-regulated the mRNA expression of caspase-3, up-regulated the protein expressions of HO-1 and NQO-1, and reduced LPO content in MPP~+-induced PC12 cells. PD98059, LY294002 or LiCl could partially reverse these changes pretreated with gastrodin combined with isorhynchophylline, suggesting that gastrodin combined with isorhynchophylline inhibited MPP~+-induced apoptosis of PC12 cells and oxidative stress through ERK1/2 and PI3 K/GSK-3ß signal pathways. Our experiments showed that gastrodin combined with isorhynchophylline could down-re-gulate the mRNA expression of caspase-3 and up-regulate the protein expressions of HO-1 and NQO-1, so as to reduce oxidative stress and inhibit apoptosis.

Brain-Heart Interactions Underlying Traditional Tibetan Buddhist Meditation.

Despite accumulating evidence suggesting improvement in one's well-being as a result of meditation, little is known about if or how the brain and the periphery interact to produce these behavioral and mental changes. We hypothesize that meditation reflects changes in the neural representations of visceral activity, such as cardiac behavior, and investigated the integration of neural and visceral systems and the spontaneous whole brain spatiotemporal dynamics underlying traditional Tibetan Buddhist meditation. In a large cohort of long-term Tibetan Buddhist monk meditation practitioners, we found distinct transient modulations of the neural response to heartbeats in the default mode network (DMN), along with large-scale network reconfigurations in the gamma and theta bands of electroencephalography (EEG) activity induced by meditation. Additionally, temporal-frontal network connectivity in the EEG theta band was negatively correlated with the duration of meditation experience, and gamma oscillations were uniquely, directionally coupled to theta oscillations during meditation. Overall, these data suggest that the neural representation of cardiac activity in the DMN and large-scale spatiotemporal network integrations underlie the fundamental neural mechanism of meditation and further imply that meditation may utilize cortical plasticity, inducing both immediate and long-lasting changes in the intrinsic organization and activity of brain networks.

ß-Ecdysterone protects SH-SY5Y cells against ß-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways.

Recently, the significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to the loss of neuroprotective estrogen after menopause. Does phytoestrogen have the ability to protect against amyloid-ß (Aß) toxicity? The aim of this study was to evaluate hypothesis that ß-ecdysterone (ß-Ecd) protects SH-SY5Y cells from Aß-induced apoptosis by separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal kinase (JNK). Here, we demonstrate that phytoestrogen ß-Ecd inhibits Aß-triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation. Interestingly, ß-Ecd upregulates Bcl-2 expression in SH-SY5Y cells under both basal and Aß-challenged conditions, but downregulates Bax expression only in Aß-challenged conditions. Subsequently, Akt-dependent NF-κB activation is required for Bcl-2 upregulation, but not Bax downregulation, in response to ß-Ecd, which was validated by the use of LY294002 and Bay11-7082. Notably, ß-Ecd attenuates the Aß-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and JNK activation without altering the basal ASK1 phosphorylation and JNK activation. ROS-scavenging by diphenyleneiodonium (DPI) abrogated the ability of ß-Ecd to alter the activation of ASK1. Simultaneously, inhibition of JNK by SP600125 abolished ß-Ecd-induced Bax downregulation in Aß-challenged SH-SY5Y cells, whereas LY294002 failed to do so. Consequently, ß-Ecd possesses neuroprotection by different and complementary pathways, which together promote a Bcl-2/Bax ratio. These data support our hypothesis and suggest that ß-Ecd is a promising candidate for the treatment of AD.

[Insulin combined with selenium inhibit p38MAPK/CBP pathway and suppresses cardiomyocyte apoptosis in rats with diabetic cardiomyopathy].

Objective To investigate the effect of insulin in combination with selenium on p38-mitogen-activated protein kinase/CREB-binding protein (p38MAPK/CBP) pathway in rats with diabetic cardiomyopathy. Methods Fifty SD rats were randomly grouped into control group, diabetic cardiomyopathy (DCM) group, diabetic cardiomyopathy with insulin treatment (DCM-In) group, diabetic cardiomyopathy with selenium treatment (DCM-Se) group, and diabetic cardiomyopathy with insulin and selenium combination treatment (DCM-In-Se) group. Flow cytometry was used to analyze cell cycle. TUNEL staining was used to detect cardiomyocyte apoptosis. Western blotting was used to examine the levels of cyclin D1, cyclin E, Bax, Bcl-2, p38MAPK, p-p38MAPK, CBP and Ku70. Co-immunoprecipitation was used to examine the acetylation status of Ku70. Results Insulin in combination with selenium significantly inhibited cardiomyocyte apoptosis, increased Bcl-2 levels and decreased Bax, cyclin D1, cyclin E, p38MAPK, p-p38MAPK, CBP, Ku70 and acetylated Ku70 levels. Conclusion The combined treatment of insulin and selenium suppresses cardiomyocyte apoptosis by inhibiting p38MAPK/CBP pathway.

Matrix solid-phase dispersion extraction followed by high performance liquid chromatography-diode array detection and ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometer method for the determination of the main compounds from Carthamus tinctorius L. (Hong-hua).

A simple and low-cost method based on matrix solid-phase dispersion (MSPD) extraction, HPLC separation, diode array detection and UPLC-Q-TOF-MS have been developed for the determination of Hydroxysafflor yellow A (HSYA), Kaempferol and other main compounds in Carthamus tinctorius. The experimental parameters that may affect the MSPD method, including dispersing sorbent, ratio of dispersing sorbent to sample, elution solvent, and volume of the elution solvent were examined and optimized. The optimized conditions were determined to be that silica gel was used as dispersing sorbent, the ratio of silica gel to sample mass was selected to be 3:1, and 10 mL of methanol: water (1:3, v:v) was used as elution solvent. The highest extraction yields of the two compounds were obtained under the optimized conditions. The method showed good linearity (r(2)≥0.999 2) and precision (RSD≤3.4%) for HSYA and Kaempferol, with the limits of detection of 35.2 and 14.5 ng mL(-1), respectively. The recoveries were in the range of 92.62-101.7% with RSD values ranging from 1.5 to 3.5%. At the meanwhile, there were 21 compounds in the extraction by MSPD method were identified by TOF-MS method to improve the quality control for safflower. Comparing to ultrasonic and soxhlet methods, the proposed MSPD procedure was more convenient and less time-consuming with reduced requirements on sample and solvent amounts. The proposed procedure was applied to analyze four real samples that were collected from different localities.

[The combined effects of insulin and selenium in improving insulin signal transduction in skeletal muscles of diabetic rats].

OBJECTIVE: To investigate the combined effects of insulin and selenium in improving the physiological parameters and insulin signal transduction in the skeletal muscles of diabetic rats. METHODS: 35 male SD rats were randomly divided into five groups: normal, diabetes, diabetes with insulin treatment (D-In group), diabetes with sodium selenite treatment (D-In-S group), and diabetes with insulin and sodium combination treatment (D-In-Se group), 7 rats in each group. The levels of blood glucose were measured using One Touch Sure Step Blood Glucose Meter. HbA1C levels were measured using microcolumn assay. The levels of insulin receptor substrate 1(IRS-1), phosphatidylinositol-3 kinase (PI3K) and glucose transporter 4(GLUT4) in skeletal muscle were examined by Western blotting and immunohistochemistry. RESULTS: Insulin combined with selenium could significantly lower blood glucose levels and markedly restore the diminished expression of in IRS-1, PI3K and GLUT4 levels in skeletal muscles of diabetic rats. CONCLUSION: There was positive cooperativity between insulin and selenium in reducing blood glucose levels in diabetic rats. The combined treatment of insulin and selenium may decrease blood glucose by upregulating IRS-1, PI3K and GLUT4 levels in skeletal muscles of diabetic rats.

[Effect of combination of insulin and selenium on insulin signal transduction in cardiac muscle of STZ-induced diabetic rats].

This study is to investigate the effect of low doses of insulin (1 u x kg(-1)) and selenium (180 microg x kg(-1)) in combination on general physiological parameters and insulin signal molecules in cardiac muscle of STZ-induced diabetic rats. The levels of blood glucose were estimated using One Touch SureStep Blood Glucose meter. HbA1c levels were estimated using microcolumn assay. TG and TC were estimated using enzymatic assay. The levels of PI3K and GLUT4 in cardiac muscle were examined by immunoblotting and immunohistochemistry. The result showed that insulin in combination with selenium could significantly lower blood glucose and blood lipid levels and markedly restored the PI3K and GLUT4 levels in cardiac muscle. It could be concluded that there was cooperation between insulin and selenium, and that treatment of diabetic rats with combined doses of insulin and selenium increased cardiac glucose uptake by upregulating the level of PI3K-mediated GLUT4 in cardiac muscle, eventually ameliorating myocardial dysfunction.