Efficacy and safety of modified Sini San for treating poststroke depression: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy and safety of modified Sini San (MSS) for poststroke depression (PSD). METHODS: Randomized controlled trials of MSS for PSD were identified in the Web of science, PsycINFO, World Cat, CNKI, VIP, Wanfang, DuXiu, and Embase databases according to the inclusion and exclusion criteria. RESULTS: In total, 7 trials with 548 patients were included in the review. The meta-analysis showed that MSS had superior effects to fluoxetine hydrochloride in terms of response rate in patients with PSD (relative risk (RR): 1.19, 95% confidence interval (CI) [1.10, 1.28], Z = 4.31, P < 0.0001). MSS may be more effective at reducing Hamilton depression rating scale (HAMD) scores and modified Edinburgh-Scandinavia stroke scale (SSS) scores than fluoxetine hydrochloride after 4 and 8 weeks of treatment. CONCLUSIONS: Our meta-analysis demonstrated that MSS appears to have excellent therapeutic effects on PSD and no serious adverse effects. However, due to the small sample sizes and low quality of the literature, studies with higher methodological quality, larger sample sizes, and placebo controls are recommended in future research on MSS in patients with PSD to enhance the strength of the evidence. Therefore, clinicians should be cautious in using this evidence to make clinical decisions.

Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells

Background and Objectives@#Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. @*Methods@#and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. @*Conclusions@#Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Bie Jia Jian Pill Combined with Bone Mesenchymal Stem Cells Regulates microRNA-140 to Suppress Hepatocellular Carcinoma Stem Cells

Background and Objectives@#Cancer stem cells (CSCs) with tumorigenic potential are reported as the crucial factors of hepatocellular carcinoma (HCC) recurrence and therapy resistance. Bone mesenchymal stem cells (BMSCs) are documented to play an important role in the protection of hepatocytes. Bie Jia Jian pill (BJJP), a Traditional Chinese Medicine, has been used to treat liver fibrosis and liver cancer. This study aimed to explore the potential role of combined use of BJJP with BMSCs in HCC cell lines. @*Methods@#and Results: Flow cytometry was used to identify BMSCs isolated from BALB/c mice and CSCs enriched from Huh7 cells by measuring CD24, CD133, CD44, CD73, CD105, CD166, CD29, CD14 and CD34. Differentiation potential of BMSCs was also determined. Cell viability and proliferation ability of CSCs were determined by CCK-8 assay and clone formation assay. The expressions of CSCs biomarkers and Wnt/β-catenin signal pathway related proteins were determined by PCR and western blot. TOP-Flash/FOP-Flash luciferase assay was applied to measure the activity of β-catenin/TCF. Compared with untreated CSCs, BJJP or BMSCs treatment alone on CSCs lead to increased miR-140 expression and cell apoptosis, as well as decreased expressions of CD24, CD133, EpCAM and cell viability.Downregualted expressions of Wnt/β-catenin signal pathway related proteins, Wnt3a and β-catenin were found in response to BJJP or BMSCs treatment alone. The combination of BJJP＋BMSCs treatment on CSCs could further enhance the suppressive effect on CSCs. Down-regulation of miR-140 in CSCs partially blocked the effects of BMSCs or BMSCs＋BJJP on the expressions of Wnt3a and β-catenin as well as the cell viability and apoptosis of CSCs.Reversed expression pattern was found in CSCs transfected with miR-140 overexpression. @*Conclusions@#Taken together, we demonstrate that BJJP＋BMSCs together could further enhance the suppressive effect on CSCs through regulating miR-140 and suppressing Wnt/β-catenin signal pathway. This study demonstrated the potential of BJJP＋BMSCs in therapeutic treatment of HCC.

Chinese herbal medicine Qinggongshoutao for the treatment of amnestic mild cognitive impairment: A 52-week randomized controlled trial.

INTRODUCTION: This randomized, double-blind trial aimed to test effect of a Chinese herbal medicine, Qinggongshoutao (QGST) pill, on the cognition and progression of amnestic mild cognitive impairment (aMCI). METHODS: Patients with aMCI were randomly assigned to receive QGST, Ginkgo biloba extract, or placebo for 52 weeks. The primary outcome measures were progression to possible or probable Alzheimer's disease (AD) and change in Alzheimer's Disease Assessment Scale-cognitive subscale scores; secondary outcome measures included assessments for cognition and function. RESULTS: Total 350 patients were enrolled, possible or probable AD developed in 10. There were significant differences in the probability of progression to AD in the QGST group (1.15%) compared with placebo group (10%). There was significant difference in Alzheimer's Disease Assessment Scale-cognitive subscale scores in favor of QGST over the placebo group. Secondary outcome measure (Mini-Mental State Examination) also showed benefit in QGST at end point. DISCUSSION: In patients with aMCI, QGST showed lower AD progression rate than placebo at 8.85%, and may have benefit on global cognition.

Curcumin Reduces Neuronal Loss and Inhibits the NLRP3 Inflammasome Activation in an Epileptic Rat Model.

BACKGROUND: Epilepsy is a chronic neurological disorder affecting an estimated 50 million people worldwide. Emerging evidences have accumulated over the past decades supporting the role of inflammation in the pathogenesis of epilepsy. Curcumin is a nature-derived active molecule demonstrating anti-inflammation efficacy. However, its effects on epilepsy and corresponding mechanisms remain elusive. OBJECTIVE: To investigate the effects of curcumin on epilepsy and its underlying mechanism. METHOD: Forty Sprague Dawley rats were divided into four groups: (1) control group; (2) Kainic Acid (KA)-induced epilepsy group; (3) curcumin group; and (4) curcumin pretreatment before KA stimulation group. Morris water maze was utilized to assess the effect of curcumin on KA-induced epilepsy. The hippocampi were obtained from rats and subjected to western blot. Immunohistochemistry was conducted to investigate the underlying mechanisms. RESULTS: Rats received curcumin demonstrated improvement of recognition deficiency and epilepsy syndromes induced by KA. Western blot showed that KA stimulation increased the expression of IL-1ß and NLRP3, which were reduced by curcumin treatment. Further investigations revealed that curcumin inhibited the activation of NLPR3/inflammasome in epilepsy and reduced neuronal loss in hippocampus. CONCLUSION: Curcumin inhibits KA-induced epileptic syndromes via suppression of NLRP3 inflammasome activation; therefore, offers a potential therapy for epilepsy.

Effect of Khat on apoptosis and related gene Smac/DIABLO expression in the cerebral cortex of rats following transient focal ischemia.

BACKGROUND: The leaves of the Khat shrub contain the major alkaloid compounds (cathinone) and cathine. These compounds can induce apoptosis and exacerbate the acute cerebral infarction, but the underlying mechanism is poorly understood. The present study aimed to investigate the effects of Khat treatment on the expression and cellular localization of Smac/Diablo (second mitochondrial activator of caspase) in the cortex of ischemic rat brain. METHODS: Adult male Sprague-Dawley rats were administered Khat (3g/kg) twice daily for 4 weeks, then underwent left middle cerebral artery occlusion (MCAO) for 2h and reperfusion for 3, 6 and 12h, respectively. The infarction area was evaluated with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Smac/DIABLO expression levels in experimental and control groups were examined by immunohistochemistry and Western blot. RESULTS: Khat significantly exacerbates the neurological damage compared with control (p<0.05). In addition, Khat-treatment significantly increased the number of TUNEL-positive cells 3h (p<0.01) and 12h (p<0.05) after reperfusion. Ischemia/reperfusion enhanced the release of Smac/DIABLO from the mitochondria to the cytosol after reperfusion. Such release of Smac/DIABLO was elevated after the rats were pretreated with Khat. CONCLUSIONS: Our results indicate that Khat treatment can induce apoptosis through enhancing the release of Smac/DIABLO from the mitochondria to the cytosol after transient focal ischemia which may be an important mechanism of Khat neurotoxicity. Therefore, Khat chewing should be avoided by people who have cerebrovascular problems.

[Effects of different acupuncture treatment on mean blood flow velocity of middle cerebral artery on the affected side and rehabilitation of hemiparalysis caused by cerebral infarction].

OBJECTIVE: To observe the effects of two different acupuncture treatment on cerebral blood flow velocity and early rehabilitation of hemiparalysis caused by cerebral infarction. METHODS: Eighty patients were randomly divided into an alternate acupuncture group (n = 40) and a routine acupuncture group (n = 40). Both of the groups were treated with routine neurology medicine and application of good limb position combined with acupuncture. The patients in the alternate acupuncture group were treated by opposing needling and non-opposing needling, i. e. acupuncture at acupoints on both the healthy and affected sides alternately, twice each day, respectively. The routine acupuncture group was treated by acupuncture at the affected side, once daily. Scores of Scandinavian Stroke Scale (SSS) were evaluated before and after treatment in the two groups, and the mean blood flow velocity of middle cerebral artery (MCA) on the affected side was monitored during two different acupuncture treatment by using Transcranial Doppler (TCD). RESULTS: The cured and markedly effective rate was 65.0% in the alternate acupuncture group and 37.5% in the routine acupuncture group with a significant difference between the two groups (P < 0.01). After treatment, the SSS score in the alternate acupuncture group was significantly lower than that in the routine acupuncture group (P < 0.01). The mean blood flow velocity of MCA during two different acupuncture treatment was both decreased significantly (both P < 0.05) and the mean blood flow velocity of MCA before the last treatment was decreased significantly in the alternate acupuncture group than those in the routine acupuncture group (P < 0.05). CONCLUSION: The therapeutic effect of the alternate acupuncture program for hemiparalysis caused by cerebral infarction is superior to that of the routine acupuncture program. It is suggested that the mechanism of acupuncture in treating hemiparalysis caused by cerebral infarction is to dilate cerebral blood vessels and improve cerebral perfusion.