Targeting the Nrf2-dependent mechanism of b-Ecdysterone in attenuating the motor dysfunction in the MPTP/Pro-induced Parkinson's disease mice model.

Oxidative stress is a pivotal stimulating factor in neurocyte apoptosis and has been involved in the pathogenesis of Parkinson's disease (PD). In this study, we have demonstrated that the improvement in the motor disorder of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/Pro-induced mice caused by b-Ecdysterone (b-Ecd) treatment is due to its antioxidant properties. Using open field, rotarod, and pole climbing tests, we have found that b-Ecd alleviates motor disorder in MPTP/Pro-induced mice and ultimately reduces the impairment of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra (SN). Notably, these effects of b-Ecd were not observed in Nrf2-KO mice. In addition, b-Ecd significantly reduced the formation of ROS and the level of MDA, blocked the increase of LPO, and partially reversed the GSH/GSSG ratio in MPTP/Pro-induced WT mice; however, these results were also not observed in MPTP/Pro-induced Nrf2-KO mice. Mechanistically, b-Ecd enhanced the expression levels of heme oxygenase 1 (HO-1) and GCLc, but not NQO1 (NAD(P)H quinone dehydrogenase 1) and GCLm expression. Interestingly, b-Ecd failed to increase the protein and mRNA levels of HO-1 and GCLc in Nrf2-KO mice, suggesting that b-Ecd attenuates oxidative stress through an Nrf2-dependent mechanism. Furthermore, b-Ecd promoted the expressions of PI3K/Akt phosphorylation (activity) and GSK-3b phosphorylation (inactivity). Conversely, administration of b-Ecd markedly decreased Fyn phosphorylation levels. Collectively, our findings suggest that b-Ecd focuses on Nrf2 in reducing MPTP/Pro-induced oxidative stress and subsequent motor deficits by inhibiting its nuclear export through PI3K/Akt/GSK-3b/Fyn pathway regulation. These further indicate that b-Ecd may be an absorbing therapeutic agent for PD.

Luteimonas suaedae sp. nov., a novel bacterium isolated from rhizosphere of Suaeda aralocaspica (Bunge) Freitag & Schütze.

Light yellowish-white colonies of a bacterial strain, designated LNNU 24178T, were isolated from the rhizosphere soil of halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze grown at Shihezi district, Xinjiang, PR China. Cells were Gram-stain-negative, non-flagellum-forming, rod-shaped and non-motile. The results of phylogenetic analysis based on the 16S rRNA gene sequence indicated that LNNU 24178T represented a member of the genus Luteimonas and shared the highest sequence similarity with Luteimonas yindakuii CGMCC 1.13927T (97.1 %) and lower sequence similarity (< 97.0 %) to other known species. The genomic DNA G+C content of LNNU 24178T was 68.8 %. The average nucleotide identity (ANI) values between LNNU 24178T and Luteimonas yindakuii CGMCC 1.13927T, Luteimonas mephitis DSM 12574T, Luteimonas arsenica 26-35T and Luteimonas huabeiensis HB2T were 78.7, 78.6, 78.4 and 80.0 %, respectively. The digital DNA-DNA hybridisation (dDDH) values between LNNU 24178T and L. yindakuii CGMCC 1.13927T, L. mephitis DSM 12574T, L. arsenica 26-35T and L. huabeiensis HB2T were 22.0, 22.3, 22.2 and 23.5 %, respectively. The respiratory quinone detected in LNNU 24178T was ubiquinone-8 (Q-8). The major fatty acids (> 5.0 %) of LNNU 24178T were identified as iso-C15 : 0 (33.9 %), iso-C17 : 0 (8.7 %), iso-C11 : 0 (6.2 %), iso-C16 : 0 (5.7 %), C16 : 0 (5.3 %) and summed feature 9 (iso-C17 : 1ω9c/10-methyl C16 : 0) (21.1 %). The major polar lipids of LNNU 24178T were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), one unidentified phospholipid (PL), one unidentified glycolipid (GL) and three unidentified lipids. According to the data obtained from phenotypic, chemotaxonomic and phylogenetic analyses, strain LNNU 24178T represents a novel species of the genus Luteimonas, for which the name Luteimonas suaedae sp. nov. is proposed, with LNNU 24178T (= CGMCC 1.17331T= KCTC 62251T) as the type strain.

A weapon to fight against pervasive Omicron: systematic actions transiting to pre-COVID normal.

The Coronavirus Disease-2019 (COVID-19) pandemic is not just a health crisis but also a social crisis. Confronted with the resurgence of variants with massive infections, the triggered activities from personal needs may promote the spread, which should be considered in risk management. Meanwhile, it is important to ensure that the policy responses on citizen life to a lower level. In the face of Omicron mutations, we need to sum up the control experience accumulated, adapting strategies in the dynamic coevolution process while balancing life resumption and pandemic control, to meet challenges of future crises. We collected 46 cases occurring between 2021 and 2022, mainly from China, but also including five relevant cases from other countries around the world. Based on case studies, we combine micro-view individual needs/behaviors with macro-view management measures linking Maslow's hierarchy of needs with the transmission chain of Omicron clusters. The proposed loophole chain could help identify both individual and management loopholes in the spread of the virus. The systematic actions that were taken have effectively combated these ubiquitous vulnerabilities at lower costs and lesser time. In the dynamic coevolution process, the Chinese government has made effective and more socially acceptable prevention policies while meeting the divergent needs of the entire society at the minimum costs. Systematic actions do help maintain the balance between individuals' satisfaction and pandemic containment. This implies that risk management policies should reasonably consider individual needs and improve the cooperation of various stakeholders with targeted flexible measures, securing both public health and life resumption.

Injectable hydrogels derived from marine polysaccharides as cell carriers for large corneal epithelial defects.

Injectable hydrogels have been employed for sutureless repair of corneal epithelial defects, which can perfectly fit the defect sites and minimize the associated discomfort. However, numerous hydrogels are ineffective in treating large corneal epithelial defects and still suffer from poor biocompatibility or weak applicability when used as cell carriers. Herein, hydroxypropyl chitin/carboxymethyl chitosan (HPCT/CMCS) temperature-sensitive hydrogels are fabricated, and their physicochemical properties and suitability for corneal epithelial repair are investigated. The results demonstrate that HPCT/CMCS hydrogels have excellent temperature sensitivity between 20 and 25 °C and a transparency of over 80 %. Besides, HPCT/CMCS hydrogels can promote cell proliferation and facilitate cell migration of primary rabbit corneal epithelial cells (CEpCs). A rabbit large corneal epithelial defect model (6 mm) is established, and CEpCs are transplanted into defect sites by HPCT/CMCS hydrogels. The results suggest that HPCT/CMCS/CEpCs significantly enhance the repair of large corneal epithelial defects with a healing rate of 99.6 % on day 8, while reducing inflammatory responses and scarring formation. Furthermore, HPCT/CMCS/CEpCs can contribute to the reconstruction of damaged tissues and the recovery of functional capacities. Overall, HPCT/CMCS hydrogels may be a feasible corneal cell carrier material and can provide an alternative approach to large corneal epithelial defects.

Catalpol Alleviates Depression by Inhibiting NLRP3 Inflammasome via TLR4/MAPK/NF-Kb Pathway.

Background: We aimed to explore catalpol and NF-k. The role of antidepressant and anti-inflammatory effects of b inhibitor in depression induced by chronic unpredictable mild stress (CUMS). Methods: Under the guidance of Qiqihar Medical University, from January 2020 to January 2021, the weight, sucrose consumption and rest time of mice during swimming were monitored, the neurobehavioral changes of rats under CUMS were used to determine the experimental model; ELISA detection of iNOS, ROS, caspase-1, IL-1 ß And IL-18 expression level; Western blotting detection of TLR4, MAPK and NF-κB expression level; LPS-induced cell model. INOS, NLRP3, caspase-1, IL-1 in RT-qPCR and ELISA detection models ß And IL-18 expression level; the TLR4, MAPK and NF-κB level were detected by Western blotting. Results: CUMS can make rats lose weight, reduce sucrose consumption rate and prolong rest time. Catapol can enhance this effect; In the depression model, ROS, NLRP3, NF-κ B and iNOS were up-regulated Catalpol group MAPK, NF-κ Reduced expression of B and TLR4; ROS, caspase-1, IL-1ß, IL-18 and iNOS protein increased. Cell model group TLR4, MAPK and NF-κ. The high protein content of B decreased in catalpol group. Conclusion: Catalpol acts as anti-depressant and anti-inflammatory molecule indepression induced by CUMS. Combination of catalpol with NF-κB inhibitor might play a role in the treatment of depression through regulating the neuroinflammation.

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.

A Psychological Intervention Program for Patients with Cerebral Infarction.

INTRODUCTION: Cerebral infarction is one of the most common cerebrovascular diseases. The sequelae caused by cerebral infarction, including limb paralysis, crooked mouth corners, language barriers, etc., seriously affect the patient's physical and mental health and enthusiasm for rehabilitation training. Therefore, psychological intervention has important positive significance for the rehabilitation and nursing of patients with cerebral infarction. METHODS: This is a single-blind controlled study. 168 patients with cerebral infarction who met the inclusion criteria and visited our hospital from January 2018 to January 2020 were randomly divided into a control group (n = 84) and an intervention group (n = 84). The patients in the intervention group received an additional 3-month psychological treatment on the basis of the patients in the control group. The National Institutes of Health Stroke Scale (NIHSS), Activities of Daily Living (ADL) scale, Mini-Mental State Examination (MMSE), and Hamilton Depression Rating Scale (HAMD) were measured before and after the psychological intervention. RESULTS: The 3-month psychological intervention we designed significantly reduced the NIHSS and HAMD scores of patients with cerebral infarction compared with traditional rehabilitation care for cerebral infarction, implying that our psychological intervention courses can improve patients' cognitive function and suppress patients' depression. Consistently, our psychological intervention also significantly improved ADL and MMSE scores 3 months after the onset of cerebral infarction patients, implying that this psychological intervention helped patients recover their daily functions relative to conventional care. CONCLUSION: Psychological intervention can be used as an adjunct therapy in the treatment and nursing of patients with cerebral infarction.

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.

Functional thermosensitive hydrogels based on chitin as RIN-m5F cell carrier for the treatment of diabetes.

Herein, the thermosensitive hydroxypropyl chitin (HPCT) hydrogel was prepared and the chemical structures, microstructures, rheological properties and degradation in vitro were investigated. The HPCT hydrogel possessed satisfactory biocompatibility in mouse fibroblast cells and Sprague Dawley rats. On the other hand, N-acetylglucosamine (NAG) and carboxymethyl chitosan (CMCS) provided favorable capacity for promoting cell proliferation, delaying cell apoptosis, and facilitating the insulin secretion of rat pancreatic beta cells (RIN-m5F) in three-dimensional culture. Most importantly, the effects of HPCT/NAG and HPCT/CMCS thermosensitive hydrogels as RIN-m5F cells carriers were evaluated via injection into different areas of diabetic rats. Our results demonstrated that HPCT/NAG and HPCT/CMCS hydrogels loaded RIN-m5F cells could keep cells survival, maintain insulin secretion and reduce blood glucose for one week. Overall, the functional thermosensitive hydrogels based on HPCT were effective cell carriers for RIN-m5F cells and might provide novel strategy for the treatment of diabetes via cell engineering.

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.

Regular COVID-19 Pandemic Containment in Communities: A Risk Governance Perspective.

Post COVID-19, differentiated regular management in place of strict lockdowns is more favored as a feasible option for balancing economic resumption and pandemic control. China's transition experience shows that this stage came not easily, during which regional sporadic outbreaks could re-emerge. Actually, it is an ongoing process of identifying loopholes and refining the management. Based on the IRGC risk governance framework, this article analyzes these challenges in community involvement posed by the transition. The systematic examination of the whole risk chain would be conducive to contain the virus spread, lessen the pressure of communities for the battle and enhance future responses for a possible resurgence. Unlike the emergency mode with mass mobilized, during regular control periods, community becomes the critical frontline for suppressing COVID-19 but with limited manpower and resources. Still, it can serve as a transformation platform to motivate atomized residents to take responsibility or contribute. Notably, the health governance of all people never ends. With the increased knowledge of COVID-19, the progress of pandemic control, and the needed adjustments for behavioral responses, different communities should come up with more suitable options instead of rigid management back to the old days.

[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.

Preventing the Growing Transmission of COVID Clusters: An Integration of the Maslow's Hierarchy of Needs in the Risk Chain.

PURPOSE: China's success in containing the coronavirus is an ongoing process of identifying loopholes and refining the management in the COVID-19 risk chain. This article discusses the role of personal needs in epidemic control and linked psychological needs with management measures to propose intervention advice on curbing viral transmission in a systematic way. METHODS: Based on case studies, we showed the integration of the Maslow's Hierarchy of Needs in the COVID-19 risk chain. The analysis combined the micro-view from individual needs and macro influences from governmental measures. The proposed chain of vulnerabilities could help identify critical links of COVID-19 crisis management in case that cascading effects such as super-spread can be intercepted in time. RESULTS: The article mainly focused on curbing the viral transmission timely whenever cluster of cases resurge. Considering the triggered activities from personal needs may facilitate the spread, minimizing the impact scale while managing the crisis could start with protecting vulnerable population, well governing potential hotspots, and necessary restrictions on group activities. Besides, "individual" protections combined with "institutional" solutions are strongly advocated. The worst scenario would be the governance link slackened or made mistakes, together with delayed identification, plus unprotected way of living and gathering. In order to cut the transmission in time, besides virus-blocking strategies and vaccination approach, screening measures in combination with the satisfaction of personal needs would help identify confirmed cases earlier. Publicizing the model citizen of being responsible could show needs' satisfaction can live with the virus elimination. At the emergency response stage, it is also crucial to secure fewer loopholes in the health system and strengthen the self-protection barrier by all means. CONCLUSION: China's experience offers a reference for the balance between the resurgence of clustered cases and sustained recovery. As long as the global pandemic continues, its impact on personal activities will not stop, and vice versa. The chain of vulnerabilities integrating psychological needs into the COVID-19 risk management can provide clear clues for cutting further transmission in an efficient and more socially acceptable way.

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.

Application of telehealth intervention in Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Telehealth intervention has been proposed as a sustainable and innovative intervention approach to Parkinson's disease (PD) patients, but there are still conflicting results in the literature about its effect. This study aimed to evaluate the efficacy of telehealth intervention for PD patients. METHODS: PubMed, EMBASE, CENTRAL and China National Knowledge Infrastructure (CNKI) were searched from the inception to June 2018 for randomized controlled trials (RCTs) and cohort studies, without language restrictions. When feasible, data were statistically pooled for meta-analysis using Review Manager 5.3. Otherwise, narrative summaries were used. RESULTS: Twenty-one studies were included. With respect to PD severity, compared with usual care, telehealth intervention was beneficial in lowering motor impairment of PD patients significantly (mean difference (MD) = -2.27, 95% confidence interval (95% CI) -4.25 to -0.29, p = 0.02), rather than mental status (MD = -0.98, 95% CI -2.61 to 0.65, p = 0.24), activities of daily living (MD = -1.51, 95% CI -4.91 to 1.89, p = 0.38) and motor complications (MD = -0.36, 95% CI -1.31 to 0.59, p = 0.46). Telehealth intervention did not lead to significant reduction in quality of life (standardized mean difference (SMD) = 0.04, 95% CI -0.20 to 0.28, p = 0.76), depression (SMD = -0.12, 95% CI -0.37 to 0.13, p = 0.34), cognition (MD = 0.37, 95% CI -0.34 to 1.09, p = 0.31) and balance (MD = 0.09, 95% CI -2.49 to 2.66, p = 0.95). DISCUSSION: Telehealth intervention is an effective option for individuals with PD to improve their motor impairment. Further well-designed studies are warranted to confirm our findings.

Gentiopicroside abrogates lipopolysaccharide-induced depressive-like behavior in mice through tryptophan-degrading pathway.

Targeting neuroinflammatory disturbances has been acknowledged as a potential strategy for treatment of depressive disorder in humans. Over-activation of tryptophan-degrading pathway by pro-inflammatory cytokines resulted in N-methyl-d-aspartate (NMDA)-mediated excitotoxicity, which is implicated in pathophysiology of depression. Gentiopicroside (Gent) has powerful anti-inflammatory property and exhibits promising antidepressant effect in an animal model of pain/depression dyad by down-regulating GluN2B-containing NMDA receptors. Therefore, the present study aimed to investigate the ability of Gent to abolish depressive-like behavior induced by lipopolysaccharide (LPS) in mice. Acute administration of LPS (0.5 mg/kg, i.p.) increased immobility time in both forced swimming test (FST) and tail suspension test (TST) without affecting spontaneous locomotor activity, indicative of depressive-like behavior. Gent (50 mg/kg, i.p.) administered once a day for three consecutive days prevented the development of depressive-like behavior induced by LPS. The antidepressant-like effect was paralleled with restoration of LPS-induced alterations in brain inflammatory mediators (i.e. IL-1ß and TNF-α). In addition, Gent prevented over-activation of indoleamine 2,3-double oxygen enzyme (IDO) and recovered GluN2B subunit expression in the PFC challenged by LPS. In conclusion, our results suggested that Gent pretreatment provided protection against LPS-induced depressive-like behavior and the effect appeared to be demonstrated, at least partially, by blocking various steps of tryptophan-degrading pathway.

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.

Synergistic protective effect of paeoniflorin and ß-ecdysterone against rotenone-induced neurotoxicity in PC12 cells.

There are several factors, like oxidative stress and neurons loss, involving neurodegenerative diseases such as Parkinson's disease (PD). The combination of antioxidant and anti-apoptotic agent is becoming a promising approach to fight against PD. This study evaluates the hypothesis that paeoniflorin (PF) and ß-ecdysterone (ß-Ecd) synergize to protect PC12 cells against toxicity induced by PD-related neurotoxin rotenone. The combination of PF and ß-Ecd, hereafter referred to as the PF/ß-Ecd, at suboptimal concentrations increased the viability of rotenone-exposed PC12 cells in a synergistic manner. PF and ß-Ecd cooperate to attenuate the rotenone-induced apoptosis by decrease in Bax expression, caspase-9 activity, and caspase-3 activity. PF or PF/ß-Ecd, but not ß-Ecd, inhibited rotenone-triggered protein kinase C-δkinase C-δ (PKCδ) upregulation and nuclear factor κB (NF-κB) activation. ß-Ecd or PF/ß-Ecd, but not PF, enhanced serine/threonine protein kinase (Akt) activation, promoted nuclear factor E2-related factor 2 (Nrf2) nuclear accumulation, suppressed reactive oxygen species (ROS) production. Neuroprotection of PF/ß-Ecd could be completely blocked by PKCδ inhibitor rottlerin plus Akt specific inhibitor LY294002. Dual blockade of the PKCδ/NF-κB pathway by PF and activation of Akt/Nrf2 pathway by ß-Ecd results in a synergistic neuroprotective effect against rotenone-induced neurotoxicity in vitro. These findings provide the rationale for determining the in vivo activity of combined therapy with PF and ß-Ecd against PD.

[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.