Online mindfulness-based stress reduction improves anxiety and depression status and quality of life in caregivers of patients with severe mental disorders. / ç½‘ç»œæ­£å¿µå‡åŽ‹ç–—æ³•å¯æ”¹å–„ä¸¥é‡ç²¾ç¥žéšœç¢æ‚£è€ ç §æ–™è€ ç„¦è™‘æŠ‘éƒçŠ¶æ€åŠå ¶ç”Ÿæ´»è´¨é‡.

OBJECTIVES: To explore the effects of online mindfulness-based stress reduction (MBSR) on the anxiety and depression status, and quality of life in the caregivers of patients with severe mental disorders. METHODS: Ninety-three caregivers for patients with schizophrenia or bipolar disorder, who were hospitalized in Yunnan Provincial Mental Hospital in March 2021, were enrolled and randomly divided into control group (n=47) and MBSR intervention group (n=46). Both groups received basic health education and rehabilitation skill training, while the intervention group received additional online MBSR for 8 weeks. The anxiety and depression status, and the quality of life of the caregivers were evaluated by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 36-item Short Form Health Survey (SF-36) before and 8 weeks after intervention, respectively. RESULTS: Thirteen caregivers dropped out of the study, and 80 subjects (40 in each group) were included in the final analysis. At the baseline, there were no significant differences in SAS, SDS and SF-36 scores between two groups (all P>0.05). Compared with the baseline, SAS and SDS scores in the intervention group significantly decreased after 8 weeks of intervention (both P<0.01) and were significantly lower than those in the control group (both P<0.01). There were no significant changes in the control group (all P>0.05). Except the physiological function dimension, the total score and the scores of each dimension of SF-36 in the intervention group were significantly increased after 8-week intervention (all P<0.05), and were significantly higher than those in the control group (all P<0.01). There were no significant changes in the control group before and after intervention (all P>0.05). CONCLUSIONS: Online MBSR can reduce the anxiety and depression levels, improve the quality of life in the caregivers of patients with severe mental disorders.

Integrated analysis of ceRNA network reveals potential prognostic Hint1-related lncRNAs involved in hepatocellular carcinoma progression.

BACKGROUND: Hint1 is a novel tumor suppressor gene, and inactivation of its expression is closely associated with the carcinogenesis of a variety of malignancies. The effects of Hint1 deficiency on the competing endogenous RNA (ceRNA) regulatory network in the context of HCC remains to be fully characterized. This study aims to explore Hint1-related hub lncRNAs in HCC and to establish a reliable prognostic model for HCC patients based on these hub lncRNAs. METHODS: lncRNA + mRNA microarray was used to identify differentially expressed (DE) lncRNAs and mRNAs in Huh7 cells before and after Hint1 knockdown. A Hint1-related ceRNA network was mapped by bioinformation technology. The DEmRNAs in the network were analyzed via GO and KEGG enrichment analyses. Hub DElncRNAs associated with HCC patient prognosis were then detected through univariate and multivariate Cox regression analyses and were incorporated into a prognostic model. The prognostic value of this model was then assessed through the use of Kaplan-Meier curves, time-related ROC analyses, and nomograms. We also utilized Kaplan-Meier curves to validate the relationship between hub lncRNAs and the overall survival (OS) of HCC patients. Finally, A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was mapped. RESULTS: We identified 417 differentially expressed DElncRNAs and 2096 DEmRNAs in Huh7 cells before and after Hint1 knockdown. Three hub DElncRNAs (LINC00324, SNHG3, and DIO3OS) in the Hint1-associated ceRNA network were screened out using univariate and multivariate Cox regression analyses. A hepatocellular carcinoma (HCC) prognostic risk-scoring model and nomogram were constructed using these three hub lncRNAs, and it was confirmed that the risk score of the model could be used as an independent predictor of HCC prognosis. A Hint1-related core ceRNA network based on the hub DElncRNAs and DEmRNAs was also mapped. CONCLUSION: We constructed a reliable prognostic model for HCC patients based on three Hint1-related hub lncRNAs, and we believe these three hub lncRNAs may play critical roles in hepatocarcinogenesis, and progression.

Fecal Microbiota Transplantation Alleviated Cerebral Ischemia Reperfusion Injury in Obese Rats.

This study aimed to investigate whether fecal microbiota transplantation (FMT) provides protection for stroke injury in obese patients. Rats were fed high-fat diet (HFD) for 4 weeks and subjected to middle cerebral artery occlusion (MCAO). After FMT for 30 days, body weight, serum total cholesterol and triglyceride levels, neurological score, brain water content, and cerebral infarction volume were measured. Brain reactive oxygen species, superoxide dismutase and malondialdehyde were detected and the levels of Bcl-2, Bax and cleaved caspase-3 were examined. Rats fed with HFD had higher body weight and higher serum total cholesterol and triglyceride levels. Neurological score was lower, brain water content and cerebral infarction volume were higher in obese rats following MCAO, but FMT improved neurological deficit. Moreover, oxidative stress was enhanced in obese rats following MCAO, but FMT attenuated oxidative stress. Brain Bcl-2 level was lower while Bax and cleaved caspase-3 levels were higher in obese rats following MCAO, but FMT increased brain Bcl-2 level and decreased Bax and cleaved caspase-3 levels. In conclusion, FMT attenuated cerebral ischemic injury in obese rats and the beneficial effects of FMT may be mediated by the attenuation of oxidative stress and apoptosis in the brain.

Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes.

INTRODUCTION: This study aimed to compare the therapeutic efficacy of metformin and other anti-hyperglycemic agents in hepatocellular carcinoma (HCC) patients with type 2 diabetes (T2D). MATERIALS: A systematic electronic search on keywords including HCC and different anti-hyperglycemic agents was performed through electronic databases including Medline and EMBASE. The primary outcome was the overall survival (OS). The secondary outcomes were the recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: Six retrospective cohort studies were included for analysis: Four studies with curative treatment for HCC (618 patients with metformin and 532 patients with other anti-hyperglycemic agents) and two studies with non-curative treatment for HCC (92 patients with metformin and 57 patients with other anti-hyperglycemic agents). Treatment with metformin was associated with significantly longer OS (OR1yr=2.62, 95%CI: 1.76-3.90; OR3yr=3.14, 95%CI: 2.33-4.24; OR5yr=3.31, 95%CI: 2.39-4.59, all P<0.00001) and RFS (OR1yr=2.52, 95%CI: 1.84-3.44; OR3yr=2.87, 95%CI: 2.15-3.84; all P<0.00001; and OR5yr=2.26, 95%CI: 0.94-5.45, P=0.07) rates vs. those of other anti-hyperglycemic agents after curative therapies for HCC. However, both of the two studies reported that following non-curative HCC treatment, there were no significant differences in the OS and PFS rates between the metformin and non-metformin groups (I2>50%). CONCLUSIONS: Metformin significantly prolonged the survival of HCC patients with T2D after the curative treatment of HCC. However, the efficacy of metformin needs to be further determined after non-curative therapies for HCC patients with T2D.

Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5.

Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent nontumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients. Dlg5-silencing promoted epithelial-mesenchymal transition, invadopodium formation, gelatin degradation function, and invadopodium-associated invasion of HepG2 cells. In contrast, Dlg5 overexpression inhibited epithelial-mesenchymal transition, functional invadopodium formation, and invasion of SK-Hep1 cells. Both Girdin and Tks5, but not the Tks5 nonphosphorylatable mutant, were responsible for the enhanced invadopodium formation and invasion of Dlg5-silenced HepG2 cells. Furthermore, Dlg5 interacted with Girdin and interfered with the interaction of Girdin and Tks5. Dlg5 silencing promoted Girdin and Tks5 phosphorylation, which was abrogated by Girdin silencing and rescued by inducing shRNA-resistant Girdin expression. Moreover, Dlg5 overexpression significantly inhibited HCC intrahepatic and lung metastasis in vivo. Taken together, our data indicate that Dlg5 acts as a novel regulator of invadopodium-associated invasion via Girdin and by interfering with the interaction between Girdin and Tks5, which might be important for Tks5 phosphorylation in HCC cells. Conceivably, Dlg5 may act as a new biomarker for prognosis of HCC patients.

Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity.

Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling.

Hint1 suppresses migration and invasion of hepatocellular carcinoma cells in vitro by modulating girdin activity.

Histidine triad nucleotide-binding protein 1 (Hint1) is a haploinsufficient tumor suppressor gene. Its role in cancer cell migration has not been previously speculated. In the current study, we examined the expression of Hint1 in metastatic and non-metastatic lymph nodes of hepatocellular carcinoma (HCC) patients and further elucidated the effect of Hint1 expression on girdin expression and phosphorylation of AKT and ERK1/2 and on the migration of HCC cells in vitro. Expression of Hint1 and girdin in primary HCC tissues and metastatic and non-metastatic lymph nodes was determined by RT-PCR assays. HepG2 cells were transfected with plasmid vectors overexpressing Hint1 or small interfering RNA (siRNA) targeting Hint1, girdin, Hint1 plus girdin, or the scrambled RNA. Migration and invasion of HCC cells were examined by wound and Transwell assays. Protein expression was detected by immunofluorescence and immunoblotting assays. RT-PCR assays revealed that the messenger RNA (mRNA) transcript levels of Hint1 were markedly lower than those of primary HCC tissues and non-metastatic lymph nodes (P < 0.01). By contrast, the mRNA transcript levels of girdin were significantly higher than non-metastatic lymph nodes (P < 0.05). Furthermore, siRNA knockdown of HINT1 resulted in a significant increase in the mRNA transcript levels of girdin in HepG2 cells (P < 0.05). Wound assays and Transwell assays showed that Hint1 knockdown by siRNA significantly enhanced the migration and invasion of HepG2 cells compared to HepG2 cells transfected with scrambled siRNA. Hint1 knockdown also led to significantly increased phosphorylation of girdin and AKT in HepG2 cells (P < 0.05), which, however, was effectively aborted by girdin knockdown by siRNA (P < 0.05). Hint1 is downregulated in metastatic lymph nodes and is implicated in migration and invasion of HCC cells in vitro by modulating girdin and AKT expression and phosphorylation. The Hint1-girdin-AKT signaling axis should be further dissected for its role in HCC migration and invasion and may be therapeutically targeted to suppress tumor growth and metastasis.

Progress in The Research of Lactate Metabolism Disruption And Astrocyte-Neuron Lactate Shuttle Impairment in Schizophrenia: A Comprehensive Review.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder widely recognized for its impaired bioenergy utilization. The astrocyte-neuron lactate shuttle (ANLS) plays a critical role in brain energy supply. Recent studies have revealed abnormal lactate metabolism in SCZ, which is associated with mitochondrial dysfunction, tissue hypoxia, gastric acid retention, oxidative stress, neuroinflammation, abnormal brain iron metabolism, cerebral white matter hypermetabolic activity, and genetic susceptibility. Furthermore, astrocytes, neurons, and glutamate abnormalities are prevalent in SCZ with abnormal lactate metabolism, which are essential components for maintaining ANLS in the brain. Therefore, an in-depth study of the pathophysiological mechanisms of ANLS in SCZ with abnormal lactate metabolism will contribute to a better understanding of the pathogenesis of SCZ and provide new ideas and approaches for the diagnosis and treatment of SCZ.

Increased intestinal bile acid absorption contributes to age-related cognitive impairment.

Cognitive impairment in the elderly is associated with alterations in bile acid (BA) metabolism. In this study, we observe elevated levels of serum conjugated primary bile acids (CPBAs) and ammonia in elderly individuals, mild cognitive impairment, Alzheimer's disease, and aging rodents, with a more pronounced change in females. These changes are correlated with increased expression of the ileal apical sodium-bile acid transporter (ASBT), hippocampal synapse loss, and elevated brain CPBA and ammonia levels in rodents. In vitro experiments confirm that a CPBA, taurocholic acid, and ammonia induced synaptic loss. Manipulating intestinal BA transport using ASBT activators or inhibitors demonstrates the impact on brain CPBA and ammonia levels as well as cognitive decline in rodents. Additionally, administration of an intestinal BA sequestrant, cholestyramine, alleviates cognitive impairment, normalizing CPBAs and ammonia in aging mice. These findings highlight the potential of targeting intestinal BA absorption as a therapeutic strategy for age-related cognitive impairment.

Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity.

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.

The Connection of Early Life Adversity and Post Traumatic Stress Disorder: an Updated Review.

Human beings develop a highly coordinated and flexible system of social behavior and threat evaluation. In this review we focus on the unique role of early life adversity (ELA) in programming deficits in social behavior and threat processing, and provides guidance on future investigations in the areas of stress reactivity and mental health. We propose that neuroendocrine perturbations of hypothalamus-pituitary-adrenal (HPA) axis and gene activity by epigenetic mechanisms may explain how early adverse circumstances may lead to post traumatic stress disorder (PTSD). The detailed exploration of the interaction of stress as environmental factor and epigenetic and genetic regulation in HPA axis may improve targeted interventions among vulnerable individuals. We are convinced that further studies following these directions will contribute to effective prevention and treatment of PTSD in early traumatized patients.

Association of Essential Tremor With Dementia and Affective Disorders: A Meta-Analysis.

Background: The dementia and affective disorders are common non-motor features in patients with essential tremor (ET). However, the relationship of ET with cognitive impairments and affective disorders remains controversial. This meta-analysis aimed to analyze the association of ET with dementia and affective disorders. Methods: Original studies published from January 1999 to October 2019 were systematically searched from the database of Medline (OvidSP), EMBASE (OvidSP), and the Cochrane Central Register of Controlled Trials. Pooled standard mean difference (SMD, random effect model), odds ratios (ORs), relative risk (RR), and 95% CI were calculated. Results: Compared with the Non-ET group, patients with ET had significantly lower Mini-Mental State Examination (MMSE) score (SMD, -1.16; 95% CI, -1.75 to -0.58; p = 0.0001) and had significantly higher depressive and anxiety symptoms scale score (SMD, 0.55; 95% CI, 0.22-0.87; p = 0.0009). The OR for dementia and affective disorders in individuals with ET compared with individuals without ET was 2.49 (95% CI, 2.17-2.85, p < 0.00001). While there was no significant difference in Montreal Cognitive Assessment (MoCA) score between ET and Non-ET groups (SMD, -0.52; 95% CI, -0.16 to 0.13; p = 0.23), there was a significant difference in the risk of mortality between ET and Non-ET groups (RR = 4.69, 95% CI, 2.18-10.07). Conclusion: The non-motor symptoms should not be neglected among patients with ET. However, the causal relationship between ET and dementia, depression, and anxiety is unclear.

Ischemic postconditioning exerts neuroprotective effect through negatively regulating PI3K/Akt2 signaling pathway by microRNA-124.

Ischemic stroke is a serious threat to human life and health, which is often accompanied by cerebral ischemia-reperfusion (I/R) injury in clinic. Ischemic postconditioning (IPostC) is a short period of mild non-fatal ischemia in the early stage of cerebral I/R injury. However, there are few reports about the protective effect of IPostC. In the present study, we investigated the neuroprotective effect of IPostC in a mice model of ischemia induced by the middle cerebral artery occlusion (MCAO). MicroRNA-124(miR-124) is a small RNA highly expressed in the brain. Several studies have shown that miR-124 is significantly decreased in IPostC. Therefore, we hypothesize that IPostC may play an important role by downregulating the expression of miR-124. Mice were treated with cerebral I/R and IPostC treatment on the basis of MCAO. The results showed that IPostC significantly reduced neurobehavioral deficits and decreased brain infarct volume. Moreover, we also found that inhibiting miR-124 effectively reduced neurons/cells apoptosis in vivo and vitro. In addition, western blot analysis of apoptosis-related proteins and PI3K/Akt2 signaling pathway proteins showed that downregulation of miR-124 significantly decreased the expression of Caspase-3 and BAX, and increased the expression of anti-apoptotic protein Bcl-2. Inhibition of miR-124 also increase PI3K/Akt/mTOR signaling pathway, thus inhibiting cell apoptosis and autophagy. However, overexpression of miR-124 weakens the protective effect of IPostC. These observations suggest that IPostC exerts its neuroprotective effect through negatively regulating PI3K/Akt2 signaling pathway by miR-124.

Depression was associated with apolipoprotein E ε4 allele polymorphism: A meta-analysis.

OBJECTIVES: Previous studies have reached different conclusions regarding an association between apolipoprotein E (APOE) polymorphisms and depression. This meta-analysis was designed to clarify these controversies. MATERIALS AND METHODS: Literatures were identified reviewing the national and international databases. The eligible articles for meta-analysis were determined by quality assessment and implementation of inclusion/exclusion criteria. This meta-analysis was performed using Review Manager 5.2 software. The odds ratios (ORs) with corresponding 95% confidence interval (CIs) were calculated using a fixed effects model. Funnel plots and Egger's regression tests were used to assess the publication bias. RESULTS: A total of nine studies that met the inclusion criteria were identified by performing a comprehensive search on the association between APOE polymorphisms and depression. APOE ε4 allele was significantly associated with depression (allele: OR=1.36, 95%CI=1.11-1.66, P=0.003; dominant: OR=1.34, 95%CI=1.06-1.68, P=0.001; recessive: OR= 1.11, 95%CI =0.45-2.76, P=0.82). HAMD scores were higher in depression patients with-APOE ε4 genotype than who without-APOE ε4 genotype (OR=0.96, 95%CI=0.16-1.76, P=0.02). CONCLUSION: APOE ε4 allele increased the depression risk; depressive patients carrying APOE ε4 allele had more severe depressive symptoms.

Bioinformatics analysis of differentially expressed genes in hepatocellular carcinoma cells exposed to Swertiamarin.

Aim: To explore gene expression profiling in hepatocellular carcinoma (HCC) cells exposed to swertiamarin. Methods: Cell viability, apoptosis and invasion were examined in HepG2 cells after swertiamarin treatment. Tumor growth of SK-Hep-1 cells xenografted in nude mice was monitored after swertiamarin treatment. Total RNA was isolated from HepG2 cells treated with swertiamarin for microarray analysis. The data of microarray were analyzed by bioinformatics. Results: Swertiamarin treatment decreased the viability and invasion while increased the apoptosis of HepG2 cells, and significantly inhibited the growth of SK-Hep-1 cells xenografted in nude mice. Pathway and biological process analysis of differentially expressed genes (DEGs) in swertiamarin treated HepG2 cells showed that PI3k-Akt was the most significant regulated pathway. 47 targets of swertiamarin were predicted by CGBVS while 21 targets were predicted by 3NN. Notably, 8 targets were predicted as the targets of swertiamarin by both programs, including two prominent targets JUN and STAT3. A large range of DEGs induced by swertiamarin could be regulated by JUN and STAT3. Conclusion: Swertiamarin treatment led to significant changes in the expression of a variety of genes that modulate cell survival, cell cycle progression, apoptosis, and invasion. Moreover, most of these genes can be clustered into pathway networks such as PI3K, JUN, STAT3, which are predicted targets of swertiamarin. Further confirmation of these targets will reveal the anti-tumor mechanisms of swertiamarin and facilitate the development of swertiamarin as a novel agent for cancer prevention and treatment.

Effect and safety of sorafenib in patients with intermediate hepatocellular carcinoma who received transarterial chemoembolization: A retrospective comparative study.

AIM: To evaluate the safety and efficacy of sorafenib plus transarterial chemoembolization (TACE) treatment for intermediate hepatocellular carcinoma (HCC). METHODS: Sixty-seven patients with intermediate-stage [Barcelona Clinic liver cancer stage B (BCLC-B)] HCC who were treated with sorafenib plus TACE or TACE alone between 2009 and 2011 were included in the study. Follow-up was until 2014 or patient death. Two groups were defined in the experiment: The experimental group, treated with sorafenib plus TACE, and the control group, treated with standard TACE alone. RESULTS: The Kaplan-Meier survival analysis showed that the median overall survival (mOS) of the experimental group was 35.2 mo, while that of the control group was 22.0 mo (P < 0.05). Sorafenib plus TACE showed higher incidence rates of rash, hand-foot syndrome (HFS), and hypertension (P < 0.05) than TACE treatment alone. CONCLUSION: Sorafenib plus TACE treatment for BCLC-B HCC significantly prolonged the mOS of patients compared to TACE treatment alone. The most common toxicities with sorafenib were rash (31.6%), HFS (39.5%) and hypertension (31.6%), but there were no intolerable adverse events. The Cox multivariate analysis showed that the survival of patients with BCLC-B HCC depended on the Child-Pugh classification, tumor diameter, and treatment with sorafenib plus TACE compared to TACE alone.

Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression.

Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. The effects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expression in HepG2 cells. Moreover, oral administration with Taraxasterol did not affect body weight, urinary protein levels, and the heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor in vivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1 expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of human liver cancer. KEY MESSAGES: Taraxasterol inhibits growth and induces apoptosis in human liver cancer cells. Taraxasterol enhances Hint1 expression by promoting demethylation in Hint1 promoter. Taraxasterol increases Hint1 levels to regulate Bax, Bcl2, and cyclinD1 expression. The effects of Taraxasterol are abrogated by Hint1 silencing in liver cancer cells. Taraxasterol inhibits the growth of subcutaneously implanted liver cancers in mice.

Scutellarin may alleviate cognitive deficits in a mouse model of hypoxia by promoting proliferation and neuronal differentiation of neural stem cells.

OBJECTIVES: Scutellarin, a flavonoid extracted from the medicinal herb Erigeron breviscapus Hand-Mazz, protects neurons from damage and inhibits glial activation. Here we examined whether scutellarin may also protect neurons from hypoxia-induced damage. MATERIALS AND METHODS: Mice were exposed to hypoxia for 7 days and then administered scutellarin (50 mg/kg/d) or vehicle for 30 days Cognitive impairment in the two groups was assessed using the Morris water maze test, cell proliferation in the hippocampus was compared using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry, and hippocampal levels of nestin and neuronal class III ß-tubulin (Tuj-1) were measured using Western blotting. These results were validated in vitro by treating cultured neural stem cells (NSCs) with scutellarin (30 µM). RESULTS: Treating mice with scutellarin shortened escape times and increased the number of platform crossings, it increased the number of BrdU-positive proliferating cells in the hippocampus, and it up-regulated expression of nestin and Tuj-1. Treating NSC cultures with scutellarin increased the number of proliferating cells and the proportion of cells differentiating into neurons instead of astrocytes. The increase in NSC proliferation was associated with phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, while neuronal differentiation was associated with altered expression of differentiation-related genes. CONCLUSION: Scutellarin may alleviate cognitive impairment in a mouse model of hypoxia by promo-ting proliferation and neuronal differentiation of NSCs.

Neuroprotection induced by post-conditioning following ischemia/reperfusion in mice is associated with altered microRNA expression.

Ischemic preconditioning and ischemic postconditioning (IPostC) represent promising strategies to reduce ischemia-reperfusion (I/R) injury and attenuate the lethal ischemic damage following stroke. However, the mechanism underlying this attenuation remains to be elucidated. It was hypothesized that alterations in microRNA (miRNA) expression in the cerebral cortex and hippocampus of mice following I/R is associated with the functional improvement induced by IPostC. Behavioral changes were assessed in a mouse model of I/R in the absence or presence of IPostC, followed by microarray analyses to investigate the expressional alterations of miRNAs in the cerebral cortex and hippocampus of mice. The results of the present study revealed that IPostC abrogated the neurological impairment and hippocampus­associated cognitive deficits induced by I/R, and upregulated or downregulated the expression levels of numerous miRNAs. Furthermore, the upregulation of miR­19a, and the downregulation of miR­1, let­7f and miR­124 expression levels following IPostC was confirmed utilizing reverse transcription­quantitative polymerase chain reaction. The results of the present study demonstrated that alterations in miRNA expression in the cerebral cortex and hippocampus of mice following I/R was associated with the neuroprotection induced by IPostC.

Scutellarin Alleviates Behavioral Deficits in a Mouse Model of Multiple Sclerosis, Possibly Through Protecting Neural Stem Cells.

Scutellarin, a flavonoid extracted from an herbal medication (Erigeron breviscapus Hand-Mazz), has been shown to protect neurons against damage and to promote neurogenesis, and thus has therapeutic potential in the treatment of a variety of neurodegenerative diseases. Since neural stem cells (NSCs) could differentiate into myelin-producing oligodendrocytes, we speculate that scutellarin could also be used to treat multiple sclerosis (MS). In the current study, we examined potential effects of scutellarin using a mouse model of MS. Briefly, adult C57BL/6 mice exposed to cuprizone (8 mg/day through diet, for 6 consecutive weeks) randomly received scutellarin (50 mg/kg/day) or vehicle for 10 consecutive days. In the scutellarin-treated group, rotarod testing at the end of the treatment showed significant improvement of motor function (increased time to fall); myelin basic protein (MBP) staining of the corpus callosum revealed decreased demyelination; TUNEL staining followed by Nestin or Sox2 staining revealed increased number of NSCs and decreased rate of NSC apoptosis in the subventricular zone (SVZ) of the lateral ventricles (LV). In a series of experiments using cultured NSCs subjected to cuprizone injury, we confirmed the protective effects of scutellarin. At 30 µM, scutellarin increased the commitment of NSCs to the oligodendrocyte and neuronal lineages, as evidenced by NG2 chondroitin sulfate proteoglycan (NG2) and doublecortin (DCX) staining. Differentiation into astrocytes (as revealed by glial fibrillary acidic protein (GFAP) staining) was decreased. Maturation of the NSCs committed to the oligodendrocyte lineage, as evidenced by oligodendrocyte marker O4 antibody (O4) staining and MBP staining, was also promoted by scutellarin. Further analysis revealed that scutellarin might suppress the phosphorylation of p38 in cuprizone-induced NSCs. In summary, scutellarin could alleviate motor deficits in a mouse model for MS, possibly by inhibiting NSC apoptosis and promoting differentiation of NSCs to myelin-producing oligodendrocytes.