Improving the anti-tumor effect of EGCG in colorectal cancer cells by blocking EGCG-induced YAP activation.

(-)-Epigallocatechin-3-gallate (EGCG) is the primary active ingredient in green tea and has been used for cancer prevention in clinical trials. The anti-tumor effects of EGCG stem from its ability to inhibit the activities of many oncoproteins, such as AKT, VEGFR, STAT3, and mutant p53. However, the clinical efficacy of EGCG is unsatisfactory. How to improve the anti-tumor effects of EGCG is an open question. Here we report that EGCG inhibits the tumor suppressive Hippo signaling pathway and activates downstream YAP in colorectal cancer (CRC) cells. Activation of YAP impedes the anti-tumor effects of EGCG. YAP blockade increases the sensitivity of CRC cells to EGCG treatment.

Ghrelin inhibits IKKß/NF-κB activation and reduces pro-inflammatory cytokine production in pancreatic acinar AR42J cells treated with cerulein.

BACKGROUND: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis (AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKKß/NF-κB signaling and pro-inflammatory cytokine production. METHODS: Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKKß/NF-κB activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-α and IL-1ß levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKKß, and p-IKKß were detected by Western blotting. RESULTS: In rat AP models, AP severity was correlated with increased IKKß/NF-κB activation, pro-inflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-α and IL-1ß as well as IKKß/NF-κB signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. CONCLUSIONS: Serum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKKß/NF-κB signaling pathway.

Prognostic value of preoperative serum bilirubin levels in ovarian cancer.

Bilirubin is a promising prognostic factor for non-liver disease-related deaths in various cancers. We investigated the association between preoperative serum bilirubin levels and oncological outcomes in patients with ovarian cancer. We retrospectively analyzed the clinical data of 282 patients with epithelial ovarian carcinoma (EOC), and grouped them according to optimal threshold values of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBL) measured by receiver operating characteristic curve analysis. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various parameters that might affect overall survival (OS) and progression-free survival (PFS) in patients with EOC. The optimal cutoff values for TBIL, DBIL, and IBIL levels were 9.65 µmol/L, 2.95 µmol/L, and 6.75 µmol/L, respectively. Increased TBIL, DBIL, and IBIL levels correlated with the serum carbohydrate antigen (CA)-125 levels, International Federation of Gynecology and Obstetrics stage, and pathological differentiation (all P<0.05). Univariate analysis revealed longer OS and PFS in patients with high TBIL (≥9.65 µmol/L) and IBIL (≥6.75 µmol/L) levels (P<0.05). Multivariate analysis showed that patients with high IBIL levels (≥6.75 µmol/L) had significantly longer OS and PFS than those with low IBIL levels (<6.75 µmol/L) [hazard ratio (HR) = 0.333, 95% confidence interval (CI): 0.123~0.904, P<0.05; HR = 1.814, 95% CI: 1.169~2.816, P<0.05]. Therefore, IBIL is a potential independent prognostic factor for OS and PFS in patients with EOC. The higher the IBL level, the better the prognosis of patients with EOC.

Reciprocal Regulation Between Indoleamine 2,3-Dioxigenase 1 and Notch1 Involved in Radiation Response of Cervical Cancer Stem Cells.

Cervical cancer is the fourth most common cancer in women around the world. Cancer stem cells (CSCs) are responsible for cancer initiation, as well as resistance to radiation therapy, and are considered as the effective target of cancer therapy. Indoleamine 2,3-dioxygenase 1 (IDO1) mediates tryptophan metabolism and T cell suppression, but the immune-independent function of IDO1 in cancer behavior is not fully understood. Using tumorsphere cultivation for enriched CSCs, we firstly found that IDO1 was increased in HeLa and SiHa cervical cancer cells and in these two cell lines after radiation treatment. The radiosensitivity of HeLa and SiHa tumorsphere cells was increased after the inhibition of IDO1 through RNA interference or by the treatment of INCB-024360, an IDO1 inhibitor. With the treatment of kynurenine, the first breakdown product of the IDO1-mediated tryptophan metabolism, the radiosensitivity of HeLa and SiHa cells decreased. The inhibition of Notch1 by shRNA downregulated IDO1 expression in cervical CSCs and the binding of the intracellular domain of Notch (NICD) on the IDO1 promoter was reduced by Ro-4929097, a γ-secretase inhibitor. Moreover, the knockdown of IDO1 also decreased NICD expression in cervical CSCs, which was correlated with the reduced binding of aryl hydrocarbon receptor nuclear translocator to Notch1 promoter. In vivo treatment of INCB-0234360 sensitized SiHa xenograft tumors to radiation treatment in nude mice through increased DNA damage. Furthermore, kynurenine increased the tumorsphere formation capability and the expression of cancer stemness genes including Oct4 and Sox2. Our data provide a reciprocal regulation mechanism between IDO1 and Notch1 expression in cervical cancer cells and suggest that the IDO1 inhibitors may potentially be used as radiosensitizers.

Down-regulation of DJ-1 Augments Neuroinflammation via Nrf2/Trx1/NLRP3 Axis in MPTP-induced Parkinson's Disease Mouse Model.

Microglia-mediated neuroinflammation plays a significant role in the pathogenesis of Parkinson's disease (PD). Down-regulation of DJ-1, a PD-associated protein, has been recently found to increase microglial sensitivity to lipopolysaccharides (LPS). However, the role of DJ-1 in microglia-mediated neuroinflammation in PD remains unclear. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish a PD model with mice and tyrosine hydroxylase (TH) staining was performed to validate the model. Adenovirus strategy and shRNA was employed to knockdown the expression of DJ-1 in mice and BV2 microglia, respectively. Western Blot and quantitative PCR were carried out to determine the expression of cytokines, DJ-1, Nrf2, Trx1 and NRLP3. Immunoprecipitation was used to examine the potential interaction between DJ-1 and Nrf2 or Trx1. Flow cytometry-based Annexin V/7-AAD assay were performed to evaluate cell apoptosis. We found that down-regulation of DJ-1 exacerbated neuroinflammation in PD mice. DJ-1 and Nrf2 knockdown promoted inflammation and cell apoptosis in BV2 microglia, while NLRP3 knockdown had opposite effects. Furthermore, DJ-1 regulated the expression of NLRP3 by upregulating Nrf2/Trx1 axis. Taken together, these data suggested that down-regulation of DJ-1 accelerated microglia-mediated neuroinflammation and cell apoptosis via Nrf2/Trx1/NLRP3 axis. Thus, our results demonstrated the important role of DJ-1 in PD pathogenesis and warranted further investigation of DJ-1 as a therapeutic target for PD.

Prognostic value of AKAP13 methylation and expression in lung squamous cell carcinoma.

Aim: This study aimed to analyze the prognostic value and clinical significance of AKAP13 mRNA expression and AKAP13 methylation in lung squamous cell carcinoma (LUSC). Materials & methods: The mRNA expression and methylation of AKAP13 data of LUSC patients were downloaded from the Broad GDAC Firehose database and analyzed. Results:AKAP13 mRNA expression was downregulated and methylation was upregulated in LUSC tissue. Three CpG sites of AKAP13 were associated with overall survival. Combination of AKAP13 mRNA and methylation revealed 11 CpG sites associated with overall survival of LUSC patients. AKAP13 mRNA expression was associated with distant metastasis of LUSC, no associations were found between methylation status of CpG sites and clinical features. Conclusion:AKAP13 mRNA and its methylated CpG sites are potential prognostic indicators in LUSC patients.

Efficacy and Safety of Chinese Herbal Medicine for Primary Intracerebral Hemorrhage: A Systematic Review of Randomized Controlled Trials.

Background: Primary intracerebral hemorrhage (ICH) is the most harmful subtype of stroke, but there have yet been no specific proven therapies. Chinese herbal medicine (CHM) has been used for ICH for more than a thousand years; however, currently it is still lacking of available evidence. The objective of this study is to assess the current available evidence of CHM for acute ICH according to randomized controlled trials. Methods: Eight databases were searched from the year of their respective inception to November 2017. Only the studies that assessed at least four domains with "yes" according to the Cochrane risk of bias tool were selected for analysis. All the data were analyzed by using Review Manager 5.3 software. P < 0.05 was considered to be statistically significant. Results: Forty-five studies with 4,517 individuals were identified. CHM paratherapy can improve dependency, neurological function deficit, volume of hematoma, clinical effective rate, and volume of perihematomal edema compared with CHM alone or placebo (all P < 0.05). By contrast, it was not significant for improving the mortality rate of ICH patients (P > 0.05). In addition, adverse events were reported in 16 studies, whereas 29 studies did not mention it. The frequency of adverse events was 70/972 in the trial group and 48/944 in the control group. Conclusion: The present study provided supportive evidence of CHM for improving dependency of ICH and showed generally safety; however, there is still lack of evidence for improving mortality rate, and it opens for further study.

The role of mesh technology with tumor prosthesis reconstruction to reconstruct the extensor mechanism of knee joint after resection of proximal tibial tumors.

PURPOSE: The aim of this study was to evaluate the role of mesh technique in the reconstruction of the extensor mechanism after resection of proximal tibial tumors. METHODS: We retrospectively analyzed the cases of 14 patients who were diagnosed with proximal tibial tumors at our center and reconstructed with tumor prosthesis, gastrocnemius muscle, and mesh between 2012 and 2017. The treatment strategies for patellar tendon reconstruction primarily involve gastrocnemius reconstruction to cover the tumor prosthesis and mesh reconstruction for the patellar ligament. RESULTS: Among the 14 patients, the mean was 1.57° (range 0-12°) for active extension versus 105.00° (range 80-120°) for active flexion. The mean for passive extension was 0°. The passive flexion mean was 115.00° (range 90-120°). The extensor lag averaged 1.57° (range 0-12°), and the mean Musculoskeletal Tumor Society score (MSTS) was 23.57 (range 19-27). The average follow-up for all patients was 23.50 months (range 14-37). During the recent follow-up, all patients were able to walk without crutches. Two patients underwent above-the-knee amputation for local recurrence of the tumor, and lung metastasis occurred in three patients after operation. There were no postoperative complications. CONCLUSIONS: Extensor lag was remarkably reduced in the surgery group in comparison to previous study reports. Surgical resection is a simple, reliable, and effective method to remove and control the tumor. Mesh reconstruction of patellar ligament is effective to reconstruct the extensor mechanism of the knee after excision of tumor.

Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation.

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44⁺ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G¹ phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

Effect of fermented Cordyceps sinensis on doxorubicin­induced cardiotoxicity in rats.

Cordyceps sinensis (CS) is a prominent medicinal herb in traditional Chinese medicine, and fermented CS is frequently used as a substitute for natural CS. Doxorubicin (DOX), an antitumor drug used in chemotherapy, is limited by its poor cardiotoxicity. The aim of the present study was to evaluate the protective effect of fermented CS against DOX­induced cardiotoxicity and the potential underlying mechanisms. Male Sprague­Dawley rats (180­200 g) were randomly assigned to seven different treatment groups: Normal control, DOX control, DOX+captopril (0.05 g/kg), 0.75, 1.5 and 3 g/kg DOX+CS, and the CS (1.5 g/kg) control. Histopathological changes, cardiac energy metabolism, cyclic adenosine monophosphate (cAMP) signaling and the associated mRNA expression of AMP­activated protein kinase (AMPK) were then evaluated. Fermented CS decreased the left ventricular weight index, heart weight index and mortality; however, it increased diastolic blood pressure and mean arterial pressure. In addition, it shortened the duration of the QRS complex and Sα­T segment, decreased serum creatine kinase (CK) and aspartate aminotransferase activity, inhibited histopathological changes and reduced brain natriuretic peptide content. Treatment with fermented CS also increased the activities of superoxide dismutase and glutathione peroxidase, reduced malondialdehyde content, increased the mitochondrial activities of Na+K+­adenosine 5'­triphosphate (ATP) ase, Ca2+Mg2+­ATPase and CK, and increased the creatine phosphate/ATP ratio and AMP/ATP ratio. Furthermore, it decreased the ATP/adenosine 5'­diphosphate (ADP) ratio, upregulated AMPKα2 expression, reduced the activity of serum phosphodiesterases (PDEs) and increased myocardial cAMP content. The results of the present study demonstrated that fermented CS attenuated DOX­induced cardiotoxicity by inhibiting myocardial hypertrophy and myocardial damage, ameliorating systolic function and the antioxidant enzyme system, improving cardiac energy metabolism, depressing the activities of PDEs, and by upregulating the cAMP and AMPK signaling pathways. Thus, fermented CS may be a candidate for the prevention of DOX­induced cardiotoxicity, cardiac energy impairment and against a number of cardiac diseases.

Effect of Atractylodes macrocephala rhizoma on isoproterenol­induced ventricular remodeling in rats.

Myocardial infarction (MI) is the primary cause of ventricular remodeling (VR). The aim of the present study was to determine the effect of Atractylodis macrocephalae rhizoma (AMR) on VR induced by isoproterenol (ISO) in rats. Male Sprague Dawley rats were randomly divided into the normal control, ISO­induced and AMR groups. Rats in the ISO­induced and AMR groups were subcutaneously injected with 85 mg/kg/day ISO for two consecutive days. Compared with the ISO­induced group, AMR normalized the levels of hemodynamic parameters, markedly attenuated myocardial pathological damage, decreased the level of N­terminal prohormone of brain natriuretic peptide, and inhibited cardiac hypertrophy and myocardial fibrosis. In addition, AMR inhibited oxidative stress and activation of the rennin­angiotensin­aldosterone system (RAAS) when compared with the ISO­induced group. The results of the present study suggest that AMR may reverse VR via its antioxidative effect and inhibition of RAAS activation.

Ischemic stroke in patients with POEMS syndrome: a case report and comprehensive analysis of literature.

BACKGROUND: POEMS syndrome is a rare multi-systemic disease characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Arterial or venous thrombosis is a less-common complication of POEMS syndrome. Ischemic stroke has also been reported sporadically. However, the association between POEMS syndrome and ischemic stroke has not been entirely understood. METHODS: A case of ischemic stroke caused by cerebral vasculitis in a patient with POEMS syndrome was presented. Then a comprehensive review and analysis of the literature were performed. RESULTS: A total of 28 patients were identified. The common clinical manifestations of POEMS syndrome were rather non-specific in patients with ischemic stroke compared with those of patients without ischemic stroke. Twenty patients were found with multiple ischemic lesions (71.5%). In the 25 patients who had undergone the evaluation of cerebral arteries, nineteen patients (76.0%) were found with cerebral vasculopathy. Twelve patients (48.0%) had more than one cerebral artery involved. Ischemic events were documented in 8 patients even when they were undergoing all the therapy for ischemic stroke. Ten (55.6%) of the 18 patients who had survival data died within two years after stroke events. CONCLUSION: Comprehensive analysis of literature revealed several trends in patients with ischemic stroke and POEMS syndrome including a low survival rate and a preponderance of cerebral vasculopathy and multiple cerebral arteries affected. Ischemic stroke may be a poor outcome predictor in patients with POEMS syndrome. Further researches focusing on a larger cohort may help in better characterizing and treating this rare complication of POEMS syndrome.

Efficacy and safety of suanzaoren decoction for chronic insomnia disorder in adults: study protocol for randomised, double-blind, double-dummy, placebo-controlled trial.

BACKGROUND: Insomnia disorder is defined as a combination of dissatisfaction with sleep quantity or quality and a significant negative impact on daytime functioning. Chronic insomnia disorder refers to clinical symptoms of persistent insomnia at least three nights a week for at least 3 months. Prevalence estimates of insomnia disorder range from 12% to 20% in the adult population, with approximately 50% having a chronic course. The potential side effects of hypnotic medications hinder their clinical application. Thus, traditional Chinese medicine is considered as an alternative option for treating insomnia. OBJECTIVE: To evaluate the efficacy and safety of suanzaoren decoction (SZRD), a classic Chinese herbal prescription, for adult chronic insomnia disorder. METHODS/ANALYSIS: This is a randomised, double-blind, double-dummy, placebo-controlled clinical trial. A total of 150 patients with chronic insomnia disorder are randomised, allocated in a ratio of 1:1:1 to three groups: intervention group, control group and placebo group. The intervention group receives SZRD granule plus zolpidem tartrate (ZT) placebo; the control group receives ZT tablet plus SZRD granule placebo; and the placebo group receives ZT placebo and SZRD granule placebo. The patients receive medicine or placebo for 5 weeks and are followed up at 20 weeks. The primary outcome measures are polysomnography and Pittsburgh Sleep Quality Index. Secondary outcome measures are the Insomnia Severity Index, sleep diary and safety assessment. Outcomes will be assessed at baseline and after treatment. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16009198. pre-results.

Chinese herbal medicine adjunct therapy in patients with acute relapse of multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Many patients with multiple sclerosis (MS) resort to complementary and alternative medicine, which is used in 33%-80% of MS patients in the developed country. The purpose of this study is to assess the efficacy and safety of Chinese herbal medicine (CHM) as an adjunct therapy of patients with acute relapse of MS. METHODS: Six databases were searched for randomized-controlled trial of CHM for acute relapse of MS. The risk of bias was assessed by using the twelve criteria recommended by the Cochrane Back Review Group. The primary outcome measures of interest are the Expanded Disability Status Score, annual relapse frequency, annual relapse rate, and annual relapse interval. The secondary outcome measures are the clinical efficacy rate and adverse events. The selection criteria of high-frequency herbs for MS are those with cumulative frequency over 50%. We analyzed the data using Review Manager (version 5.3). RESULTS: A total of 1100 participants were included in the 20 studies from 2004 to 2015. The number of risk of bias which met the criteria varied from 5/12 to 7/12. The top 5 most frequently used herbs are ordinally Radix Angelicae Sinensis, Radix Glycyrrhizae, Radix Paeoniae Rubra, Radix Rehmanniae Preparata, and Bombyx Batryticatus. The meta-analysis showed a significant effect of CHM for improving Expanded Disability Status Score (P<0.01), annual relapse frequency (P<0.01) and the total clinical efficacy rate (P<0.01) compared with western conventional treatment. In analysis of annual relapse rate and annual relapse interval, there was a significant difference between CHMs and western conventional treatment (P<0.01). Adverse effects were monitored in 6 studies, and were well tolerated in all MS patients. CONCLUSIONS: The available evidence from present study supported but limited to recommend the routine use of CHM adjuvant therapy for MS because of the poor methodological quality and clinical heterogeneity. However, we identified an area that is worthy of further study. Furthermore, we selected high frequent use of CHMs as a promising candidate for further clinical application and MS trials. Further rigorous randomized-controlled trials are needed.

Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms.

Astragaloside IV (AST-IV) is a principal component of Radix Astragali seu Hedysari (Huangqi) and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (P < 0.05); seven studies for reducing the infarct volume (P < 0.05); and three or two studies for reducing the brain water content and Evans blue leakage (P < 0.05), respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties.

Synergistic effects of polydatin and vitamin C in inhibiting cardiotoxicity induced by doxorubicin in rats.

The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of superoxide dismutase (SOD) and the heart rate, attenuate myocardial pathological damage, decrease malondialdehyde (MDA) content, slightly increase arterial pressure and glutathione peroxidase (GSH-Px) activity, reduce intervals of QRS, QT, and ST, and lower free fatty acid (FFA) content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na+ K+ -ATPase, and Ca2+ Mg2+ -ATPase, elevate phosphocreatine (PCr) and adenosine triphosphate (ATP) contents, slightly increase adenosine diphosphate (ADP) and total adenine nucleotide (TAN) contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group. Meanwhile, the improvement effects on FFA content, the activities of ATPase and SOD, and contents of ATP and TAN in combination group were more obvious than those in polydatin group, and the improvement effects on arterial pressure, heart rate, interval of QRS, GSH-Px activity, and MDA, ADP, and PCr contents in combination group were slightly obvious when compared with those in polydatin group. In addition, the mRNA expression levels of AMPK-α2 and PPAR-α were slightly improved in combination group. The results illustrate that the combination of polydatin and vitamin C has the ability to enhance the myocardial protective effects by its antioxidative effect and improve energy metabolism.

An Overview of Systematic Reviews of Ginkgo biloba Extracts for Mild Cognitive Impairment and Dementia.

Ginkgo biloba extracts (GBEs) have been recommended to improve cognitive function and to prevent cognitive decline, but earlier evidence was inconclusive. Here, we evaluated all systematic reviews of GBEs for prevention of cognitive decline, and intervention of mild cognitive impairment (MCI) and dementia. Six databases from their inception to September 2015 were searched. Ten systematic reviews were identified, including reviews about Alzheimer's disease (n = 3), about vascular dementia (n = 1), about both Alzheimer's disease and vascular dementia (n = 2), about Alzheimer's disease, vascular dementia and mixed dementia (n = 3), and a review about MCI (n = 1). Based on the overview quality assessment questionnaire, eight studies were scored with at least 5 points, while the other two scored 4 points and 3 points, respectively. Medication with GBEs showed improvement in cognition, neuropsychiatric symptoms, and daily activities, and the effect was dose-dependent. Efficacy was convincingly demonstrated only when high daily dose (240 mg) was applied. Compared with placebo, overall adverse events and serious adverse events were at the same level as placebo, with less adverse events in favor of GBE in the subgroup of Alzheimer's disease patients, and fewer incidences in vertigo, tinnitus, angina pectoris, and headache. In conclusion, there is clear evidence to support the efficacy of GBEs for MCI and dementia, whereas the question on efficacy to prevent cognitive decline is still open. In addition, GBEs seem to be generally safe.

Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation.

Although it is known that isoflurane exposure or surgery leads to post-operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre-treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal-dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down-regulated the isoflurane-induced and surgery-induced enhancement in the protein levels of pro-inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)-1ß, interferon-γ and microglia marker Iba-1, and up-regulated protein levels of the anti-inflammatory cytokine IL-4 and IL-10. These findings suggest that pre-treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice.

Doxorubicin toxicity changes myocardial energy metabolism in rats.

BACKGROUND: Doxorubicin (DOX) is an antitumor antibiotics used against malignancies. But its toxicity limits the therapy of DOX. OBJECTIVE: The purpose of this study was to evaluate DOX toxicity and the alteration of energy metabolism after short term and long term treatment. METHODS: Male Sprague-Dawley rats were randomly assigned to four groups: Short term control group, short term DOX treatment group, long term control group and long term DOX treatment group. In short term treated group, rats were injected with DOX i.p. at a dose of 2.5 mg/kg every 48 h for six equal injections. In long term, treated group, rats were tail-intravenously injected with DOX at a dose of 3 mg/kg once a week for four weeks. At the end of the experiment, histopathological changes, general blood biomarkers, endogenous antioxidant enzymes, cardiac energy metabolism and related mRNA expression of AMPK signal pathway were determined. RESULTS: DOX induced prominent oxidative stress, a higher mortality rate, histological and ECG changes, obvious cardiac hypertrophy, acute cardiac damage and cardiac energy impairment in short term treatment rats. In long term treatment rats, DOX caused serious nephropathy and systolic dysfunction, terrible cardiac energy impairment, clear alteration of substrate utilization and AMPK signal pathway. CONCLUSION: DOX treatment can induce different damages after short term and long term treatment. In short term treatment group, rats experienced a terrible mortality rate about 40%, the acute cardiac damage, cardiac energy impairment and an early heart failure which are potential connected with reduction of glucose utilization. In the long term treatment group, serious nephropathy and obvious changes of mRNA expressions of AMPK signal pathway were observed. Meanwhile, the serious cardiac energy impairment and substrate utilization alteration denote an obviously heart failure. This study could be helpful to develop therapy strategies of DOX complications for clinical application.