Analysis of bioactive compounds in cinnamon leaves and preparation of nanoemulsion and byproducts for improving Parkinson's disease in rats.

Introduction: Cinnamomum osmophloeum Kanehira (C. osmophloeum), a broad-leaved tree species of Taiwan, contains phenolic acids, flavonoids, and phenylpropanoids such as cinnamaldehyde and cinnamic acid in leaves. Many reports have shown that the cinnamon leaf extract possesses anti-inflammatory, hypoglycemic, hypolipidemic and neuroprotective functions. This study aims to analyze bioactive compounds in C. osmophloeum (cinnamon leaves) by UPLC-MS/MS and prepare hydrosol, cinnamon leaf extract and cinnamon leaf nanoemulsion for comparison in improving Parkinson's disease (PD) in rats. Methods: After extraction and determination of total phenolic and total flavonoid contents, cinnamaldehyde and the other bioactive compounds were analyzed in cinnamon leaves and hydrosol by UPLC-MS/MS. Cinnamon leaf nanoemulsion was prepared by mixing a suitable proportion of cinnamon leaf extract, soybean oil, lecithin, Tween 80 and deionized water, followed by characterization of particle size and polydispersity index by dynamic light scattering analyzer, particle size and shape by transmission electron microscope, encapsulation efficiency, as well as storage and heating stability. Fifty-six male Sprague-Dawley rats aged 8 weeks were divided into seven groups with group 1 as control (sunflower oil) and group 2 as induction (2 mg/kg bw rotenone in sunflower oil plus 10 mL/kg bw saline), while the other groups including rotenone injection (2 mg/kg bw) followed by high-dose of 60 mg/kg bw (group 3) or low-dose of 20 mg/kg bw (group 4) for tube feeding of cinnamon leaf extract or cinnamon leaf nanoemulsion at the same doses (groups 5 and 6) every day for 5 weeks as well as group 7 with rotenone plus hydrosol containing 0.5 g cinnamon leaf powder at a dose of 10 mL/kg bw. Biochemical analysis of brain tissue (striatum and midbrain) was done to determine dopamine, α-synuclein, tyrosine hydroxylase, superoxide dismutase, catalase, glutathione peroxidase and malondialdehyde contents by using commercial kits, while catalepsy performed by bar test. Results and discussion: An extraction solvent of 80% ethanol was found to be the most optimal with a high yield of 15 bioactive compounds being obtained following UPLC analysis. A triple quadrupole tandem mass spectrometer with electrospray ionization mode was used for identification and quantitation, with cinnamaldehyde present at the highest amount (17985.2 µg/g). The cinnamon leaf nanoemulsion was successfully prepared with the mean particle size, zeta potential, polydispersity index and encapsulation efficiency being 30.1 nm, -43.1 mV, 0.149 and 91.6%, respectively. A high stability of cinnamon leaf nanoemulsion was shown over a 90-day storage period at 4 and heating at 100 for 2 h. Animal experiments revealed that the treatments of cinnamon leaf extract, nanoemulsion and hydrosol increased the dopamine contents from 17.08% to 49.39% and tyrosine hydroxylase levels from 17.07% to 25.59%, while reduced the α-synuclein levels from 17.56% to 15.95% in the striatum of rats. Additionally, in the midbrain of rats, an elevation of activities of superoxide dismutase (6.69-16.82%), catalase (8.56-16.94%), and glutathione peroxidase (2.09-16.94%) was shown, while the malondialdehyde content declined by 15.47-22.47%. Comparatively, the high-dose nanoemulsion exerted the most pronounced effect in improving PD in rats and may be a promising candidate for the development of health food or botanic drug.

Baicalein suppresses HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells by downregulating HER2 gene expression.

The upregulation of the HER2 oncogene is associated with a variety of human cancers and is associated with poor prognosis. Baicalein is reported to have anti-tumor activity, but the molecular mechanism of this effect in HER2-positive cancer cells has not been studied. In this study, our data showed that baicalein can inhibit the proliferation and transformation potential of ovarian cancer cells overexpressing HER2. Baicalein treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level. Baicalein acted on ovarian cancer cells overexpressing HER2 to downregulate the PI3K/Akt signaling pathway downstream of HER2 and inhibit the expression or activity of downstream targets, such as VEGF and cyclin D1 and MMP2. Oral administration of baicalein supplemented with a pharmaceutical excipient significantly inhibited the growth of HER2-overexpressing ovarian SKOV-3 cancer xenografts in mice. These results suggest that downregulation of HER2 gene expression by baicalein at the transcriptional level contributes to inhibit the in vitro and in vivo proliferation and HER2-mediated malignant transformation of HER2-overexpressing ovarian cancer cells.

Baicalein Induces G2/M Cell Cycle Arrest Associated with ROS Generation and CHK2 Activation in Highly Invasive Human Ovarian Cancer Cells.

Ovarian cancer is a lethal gynecological cancer because drug resistance often results in treatment failure. The CHK2, a tumor suppressor, is considered to be an important molecular target in ovarian cancer due to its role in DNA repair. Dysfunctional CHK2 impairs DNA damage-induced checkpoints, reduces apoptosis, and confers resistance to chemotherapeutic drugs and radiation therapy in ovarian cancer cells. This provides a basis for finding new effective agents targeting CHK2 upregulation or activation to treat or prevent the progression of advanced ovarian cancer. Here, the results show that baicalein (5,6,7-trihydroxyflavone) treatment inhibits the growth of highly invasive ovarian cancer cells, and that baicalein-induced growth inhibition is mediated by the cell cycle arrest in the G2/M phase. Baicalein-induced G2/M phase arrest is associated with an increased reactive oxygen species (ROS) production, DNA damage, and CHK2 upregulation and activation. Thus, baicalein modulates the expression of DNA damage response proteins and G2/M phase regulatory molecules. Blockade of CHK2 activation by CHK2 inhibitors protects cells from baicalein-mediated G2/M cell cycle arrest. All the results suggest that baicalein has another novel growth inhibitory effect on highly invasive ovarian cancer cells, which is partly related to G2/M cell cycle arrest through the ROS-mediated DNA breakage damage and CHK2 activation. Collectively, our findings provide a molecular basis for the potential of baicalein as an adjuvant therapeutic agent in the treatment of metastatic ovarian cancer.

Effects of inclined treadmill training on inadequate ankle control during walking in individuals after stroke: A pilot randomized controlled trial.

BACKGROUND: Inadequate ankle control influences walking ability in people after stroke. Walking on inclined surface activates ankle muscles and movements. However, the effect of inclined treadmill training on ankle control is not clear. OBJECTIVE: To investigate the effects of inclined treadmill training on ankle control in individuals with inadequate ankle control after chronic stroke. METHODS: This was a randomized single-blinded study. Eighteen participants were randomly assigned to receive 12 sessions of 30 min inclined (n = 9) or regular (n = 9) treadmill training and 5 min over-ground walking training. The outcomes included ankle control during walking, muscle strength of affected leg, walking performance, and stair climbing performance. RESULTS: Inclined treadmill training significantly improved ankle dorsiflexion at initial contact (p = 0.002), increased tibialis anterior activities (p = 0.003 at initial contact, p = 0.006 in swing phase), and decreased dynamic plantarflexors spasticity (p = 0.027) as compared with regular treadmill training. Greater improvements were also shown in stair climbing with affected leg leading (p = 0.006) and affected knee extensors strength (p = 0.002) after inclined treadmill training. CONCLUSIONS: Inclined treadmill training was proposed to improve inadequate ankle control after chronic stroke. Inclined treadmill training also improved the stair climbing ability accompanied with increased muscle strength of the affected lower extremity.

Dual down-regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells.

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down-regulating the EGFR-ErbB2/PI3K/Akt signaling pathway. The berberine-mediated inhibition of MMP-2 and MMP-9 activity could be rescued by co-treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin-mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

The resolution of carotid arterial thrombus by oral anticoagulation after IV thrombolysis for chemotherapy-induced stroke: A case report.

RATIONALE: Cancer-related stroke has been regarded as an emerging subtype of ischemic event. Acute treatment for this subtype may include the antiplatelet agents, anticoagulants, or endovascular intervention. PATIENT CONCERNS: A 63-year-old woman with sudden-onset right hemiparesis and conscious change was sent to our emergency department. The patient had underlying sigmoid adenocarcinoma and received chemotherapy FOLFIRI (FOL, folinic acid; F, fluorouracil; and IRI, irinotecan) with targeted therapy cetuximab following lower anterior resection since the diagnosis was made. DIAGNOSES: Brain magnetic resonance angiography revealed a filling defect in left carotid bulb, and neurosonography showed a thick atherosclerotic plaque (size 4.9 mm) in the left internal carotid artery on day 5 after the onset of stroke. INTERVENTIONS: During the first three hours after onset, administration of IV tissue plasminogen activator did not resolve the thrombus. Dabigatran (110 mg bid) started on day 7. OUTCOMES: The atherosclerotic plaque dissolved on day 24. The patient recovered her muscle strength but still had nonfluent speech in mild extent. LESSONS: Thrombolytic and anticoagulant medications in this patient suggested the thrombus formation with fibrin-rich content which may be attributable to both cancer and chemotherapy. Dabigatran, an oral anticoagulant, had a benefit for this subtype of ischemic stroke among patients with cancer.

Magnetic resonance imaging volumetric analysis for diabetic striatopathy with two episodes of hemichorea-hemiballism syndrome: A case report.

RATIONALE: Diabetic striatopathy (DS) is an uncommon movement disorder among diabetic patients characterized by clinical hemichorea-hemiballism with neuroimage change of the striatum. Here, we report a case of DS with relapsed hemichorea-hemiballism attacks even during euglycemic period, and the MRI changes by volumetric analysis. PATIENT CONCERNS: A 69-year-old diabetic female suffered from a relapsed episode of hemichorea-hemiballism during her euglycemic period after the treatment of hyperglycemia. DIAGNOSES: To investigate the serial MRI changes in a case with diabetic striatopathy who had clinical hemichorea-hemiballism syndrome. INTERVENTIONS: Semi-quantitative volumetric analyses from T1 images of these brain MRIs were obtained during the disease course. OUTCOMES: Besides, the negative finding of the first brain MRI during her first hospital admission, three afterward MRI examinations disclosed a waxing-and-waning mode of volume change from high-signal T1 images in left striatum. The clinical symptoms paralleled with the neuroimage changes in striatum. The MR signal volume changes were valuable for the clinical course of the hemichorea-hemiballism caused by diabetic striatopathy LESSONS:: Serial MR images for the diabetic striatopathy presented as a key pathognomonic relationship with the clinical hemichorea-hemiballism syndrome, assessed by our simplied volumetric analysis. Clinical involuntary movements may relapse and persist even with euglycemic condition as our case.

The effects of a schizophrenia pay-for-performance program on patient outcomes in Taiwan.

OBJECTIVE: To examine the effects of a schizophrenia pay-for-performance (P4P) program on the health outcomes of patients in Taiwan. DATA SOURCES: Seven years (2007-2013) of data from the National Health Insurance Administration (NHIA) databases were examined. STUDY DESIGN: P4P patients included those who were treated at participating facilities and consecutively included in the regular group (classified by the NHIA). Non-P4P patients were treated at nonparticipating facilities and never included in the regular group. The caliper matching method and a generalized estimating equation were used to estimate difference-in-differences models (baseline year 2009) and examine the short- and long-term effects of the P4P program on adverse outcomes. PRINCIPAL FINDINGS: The schizophrenia P4P program was associated with decreases in unscheduled outpatient visits (OR: 0.69, P < 0.001) and compulsory admissions (incidence rate ratio: 0.33, P < 0.05). However, this program was not associated with decreases in other outcomes including emergency department visits for any disease, admissions to an acute psychiatric ward, and readmission within 6 months. CONCLUSIONS: Although the disease management component of the P4P program can be beneficial for compulsory admissions, more sophisticated activities, such as health promotion targeting disadvantaged patients, could be implemented to reduce the occurrence of complicated adverse outcomes.

Different utilization of intensive care services (ICSs) for patients dying of hemorrhagic and ischemic stroke, a hospital-based survey.

The intensive care service (ICS) saves lives and rescues the neurological function of stroke patients. We wondered the different utilization of ICS for patients with ischemic and hemorrhagic stroke, especially those who died within 30 days after stroke.Sixty-seven patients died during 2011 to 2015 due to acute stroke (42 due to intracranial hemorrhage [ICH]; 25 due to cerebral infarct [CI]). The durations of hospital stay (hospital staying days [HSDs]) and ICS staying days (ISDs) and codes of the do-not-resuscitate (DNR) were surveyed among these medical records. Statistics included chi-square and descriptive analyses.In this study, CI patients had a longer HSD (mean 14.3 days), as compared with ICH patients (mean 8.3 days); however, the ICH patients had a higher percentage of early entry within the first 24 hours of admission into ICS than CI group (95.1% vs 60.0%, P = .003). A higher rate of CI patients died in holidays or weekends than those with ICH (44.0% vs 21.4%, P = .051). DNR, requested mainly from direct descendants (children or grandchildren), was coded in all 25 CI patients (100.0%) and 38 ICH patients (90.5%). More cases with early DNR coded within 24 hours after admission occurred in ICH group (47%, 12% in CI patients, P = .003). None of the stroke patient had living wills. Withhold of endotracheal intubation (ETI) occurred among CI patients, more than for ICH patients (76.0% vs 18.4%, P < .005).In conclusion, CI patients longer HSD, ISD, higher mortality within holidays or weekends, and higher ETI withhold; but less percentage of ICS utilization expressed by a lower ISD/HSD ratio. This ICS utilization is a key issue of medical quality for stroke care.

Patient- and Hospital-Level Determinants of Rehabilitation for In-Patient Stroke Care: An Observation Analysis.

During acute stroke care, rehabilitation usage may be influenced by patient- and hospital-related factors. We would like to identify patient- and hospital-level determinants of population-level inpatient rehabilitation usage associated with acute stroke care.From data obtained from the claim information from the National Health Insurance Administration (NHIA) in Taiwan (2009-2011), we enrolled 82,886 stroke patients with intracerebral hemorrhage and cerebral infarction from 207 hospitals. A generalized linear mixed model (GLMM) analyses with patient-level factors specified as random effects were conducted (for cross-level interactions).The rate of rehabilitation usage was 51% during acute stroke care. The hospital-related factors accounted for a significant amount of variability (intraclass correlation, 50%). Hospital type was the only significant hospital-level variable and can explain the large amount of variability (58%). Patients treated in smaller hospitals experienced few benefits of rehabilitation services, and those with surgery in a smaller hospital used fewer rehabilitation services. All patient-level variables were significant.With GLMM analyses, we identified the hospital type and its cross-level interaction, and explained a large portion of variability in rehabilitation for stroke patients in Taiwan.

Paraquat Induces Cell Death Through Impairing Mitochondrial Membrane Permeability.

Paraquat (PQ) as a Parkinsonian mimetic has been demonstrated to impair dopaminergic (DAergic) neurons and is highly correlated with the etiology of Parkinson's disease (PD) where the death of DAergic neurons has been mainly attributed to impaired mitochondrial functioning. In this study, PQ-induced cytotoxicity focusing on mitochondrial membrane permeability (MMP), which has been implicated to play a part in neurodegeneration, was investigated. Primarily, PQ-induced cytotoxicity and reactive oxygen species (ROS) were inhibited by an inhibitor of NADPH oxidase (NOX), indicating the toxic effect of PQ redox cycling. Further, dibucaine and cyclosporin A which respectively inhibit mitochondrial apoptosis-induced channels (MAC) and mitochondrial permeability transition pores (mPTP) were used and found to prevent PQ-induced mitochondrial dysfunction, such as decreased mitochondrial membrane potential and increased MMP, mitochondrial ROS, and pro-apoptotic factor release. Knockdown of bax and/or bak blocked PQ-induced mitochondrial clusterization of Bax and/or Bak and cytotoxicity, demonstrating the significance of MAC which is composed of Bax and/or Bak. This clusterization coincided with the release of mitochondrial apoptotic factors before there was an increase in inner MMP, indicating that MAC may precede mPTP formation. Besides, NOX inhibitor but not dibucaine attenuated the earlier PQ-induced cytosolic ROS formation or Bax and/or Bak clusterization indicating PQ redox cycling may account for MAC formation. In this model, we have resolved for the first that PQ cytotoxicity through redox cycling may sequentially result in increased outer (MAC) and inner (mPTP) MMP and suggested MMP could be implicated as a therapeutic target in treating neurodegenerative diseases like PD.

Utilizing Cerebral Perfusion Scan and Diffusion-tensor MR Imaging to Evaluate the Effect of Hyperbaric Oxygen Therapy in Carbon Monoxide-induced Delayed Neuropsychiatric Seqeulae- A Case Report and Literature Review.

PURPOSE: Detection of regional cerebral blood flow (rCBF) and/or brain magnetic resonance imaging (MRI) has been used to investigate functional defect of brain caused by carbon monoxide (CO) poisoning. In this report, we attempted to demonstrate the correlation of changes in brain singlephoton emission computed tomography (SPECT) and diffusion-tensor MR image (DTI) with functional improvement of severe delayed neuropsychiatric sequelae (DNS) after CO intoxication during the treatment of hyperbaric oxygen therapy (HBOT). CASE REPORT: The patient had normal activities of daily life after he recovered from acute CO poisoning. One month later, he presented symptoms of declined cognitive functioning, aphasia, apraxia, dysphagia, muscle rigidity, urine and fecal incontinence. After one course of HBOT, these symptoms improved significantly and the patient could regain most of his previous functioning. The patient's improvement was evidenced by increased rCBF in Brodmann areas 7, 8, 11 and 40, as well as higher mean fractional anisotropy (FA) value of DTI. CONCLUSION: Although the efficacy of HBOT in DNS patients is still needed to be evaluated in large clinical study, these data suggest that HBOT may be the choice to improve DNS efficiently and shorten the duration of suffering with favorable outcome.

Cancer risks among the users of ergot-derived dopamine agonists for Parkinson's disease, a nationwide population-based survey.

BACKGROUND: Factors of cancer occurrence among Parkinson disease patients are still not well known, although genetic predilection has been investigated. The aim of this study is to evaluate the medication effect of dopamine agonists of Parkinson disease on incidence of cancers from the Taiwan National Health Insurance Research Database. METHODS: We conducted a population-based nested case-control study by using the resources of the Taiwanese National Health Insurance from 1996 to 2000 and analyzed the prevalence of cancer among patients with Parkinson disease. A nested analysis was then implemented among those patients with both Parkinson disease and cancer, focusing separately on the use of ergot- and nonergot-derived-dopamine agonists. RESULTS: We reviewed 6211 patients with Parkinson's disease and found 329 patients with cancer. The ergot-derived dopamine agonists users were associated with an increased odds ratio for cancer, compared with nonergot-derived dopamine agonist users, with an adjusted odds ratio of 2.16 (95% confidence interval, 1.55-2.99). Among all the cancer types, we observed the higher occurrence of liver cancer among the ergot-derived dopamine agonist users. CONCLUSION: The association of ergot-derived-dopamine agonist use and cancers, especially the liver cancers, has provided us the information to further understand the drug-cancer interaction. We hope this result would prompt further investigations on the risk and benefit of the dopamine agonists use among the Parkinson's disease patients.

"Do not resuscitate" orders among deceased patients who received acute neurological care: an observation analysis.

There were many reports about the "do not resuscitate" (DNR) order while practicing in the critical care units and conducting hospice affairs but limited in the neurological issues. This study investigated the possible flaws in the execution of the DNR order among patients who received acute neurological care in Taiwan. Over a 3-year period, we retrospectively reviewed the medical records of 77 deceased patients with neurological conditions for DNR orders. Registry and analysis works included demography, hospital courses, DNR data, and clinical usefulness of the lab and image examinations. Sixty-seven DNR orders were requested by the patients' families, and more than half were signed by the patients' children or grandchildren. The main DNR items were chest compression, cardiac defibrillation, and pacemaker use, although several DNR patients received resuscitation. The mean duration from the coding date to death was 7.6 days. Two-thirds of the patients with DNR requests remained in the intensive care unit, with a mean stay of 6.9 days. Several patients underwent regular roentgenography and blood tests on the day of their death, despite their DNR orders. Hospital courses and DNR items may be valuable information on dealing with the patients with DNR orders. The results of this study also suggest the public education about the DNR orders implemented for neurological illnesses.

Inhibitory effects of resveratrol on PDGF-BB-induced retinal pigment epithelial cell migration via PDGFRß, PI3K/Akt and MAPK pathways.

PURPOSE: In diseases such as proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, and age-related macular degeneration, retinal pigment epithelial (RPE) cells proliferate and migrate. Moreover, platelet-derived growth factor (PDGF) has been shown to enhance proliferation and migration of RPE cells in PVR. Even resveratrol can suppress the migration and adhesion of many cell types, its effects on RPE cell migration and adhesion remain unknown. In this study, we investigated the inhibitory effects of resveratrol on RPE cell migration induced by PDGF-BB, an isoform of PDGF, and adhesion to fibronectin, a major ECM component of PVR tissue. METHODS: The migration of RPE cells was assessed by an electric cell-substrate impedance sensing migration assay and a Transwell migration assay. A cell viability assay was used to determine the viability of resveratrol treated-cells. The cell adhesion to fibronectin was examined by an adhesion assay. The interactions of resveratrol with PDGF-BB were analyzed by a dot binding assay. The PDGF-BB-induced signaling pathways were determined by western blotting and scratch wound healing assay. RESULTS: Resveratrol inhibited PDGF-BB-induced RPE cell migration in a dose-dependent manner, but showed no effects on ARPE19 cell adhesion to fibronectin. The cell viability assay showed no cytotoxicity of resveratrol on RPE cells and the dot binding assay revealed no direct interactions of resveratrol with PDGF-BB. Inhibitory effects of resveratrol on PDGF-BB-induced platelet-derived growth factor receptor ß (PDGFRß) and tyrosine phosphorylation and the underlying pathways of PI3K/Akt, ERK and p38 activation were found; however, resveratrol and PDGF-BB showed no effects on PDGFRα and JNK activation. Scratch wound healing assay demonstrated resveratrol and the specific inhibitors of PDGFR, PI3K, MEK or p38 suppressed PDGF-BB-induced cell migration. CONCLUSIONS: These results indicate that resveratrol is an effective inhibitor of PDGF-BB-induced RPE cell migration via PDGFRß, PI3K/Akt and MAPK pathways, but has no effects on the RPE cell adhesion to fibronectin.

Polymorphic Ala-allele carriers at residue 1170 of HER2 associated with Parkinson's disease.

OBJECTIVE: HER2, a receptor tyrosine kinase, was originally identified based on its role in cancer research. The protein has subsequently received attention for its role in nerve injury and neurodevelopment. We investigated the polymorphic association of HER2 variants at amino acid residues 655 and 1170 with Parkinson's disease (PD), a neurodegenerative disorder. DESIGN AND METHODS: Polymerase chain reaction (PCR) was used to amplify DNA samples from PD patients and control subjects. The resulting PCR fragments, which spanned HER2 residues 655 and 1170, were analyzed by restriction fragment length polymorphism and/or direct nucleotide sequencing. RESULTS: The genetic distribution at residue 655 in PD patients did not differ from that in controls. However, homozygosity for genes encoding Pro at residue 1170 (Pro/Pro) occurred at a significantly lower rate among PD subjects. In other words, Ala-allele carries higher frequency in PD, especially among female PD subjects. CONCLUSION: Different signals or potency of the kinase activities resulting from the Ala1170Pro allele of HER2 may be associated with vulnerability to stress on dopaminergic neurons in PD.

Effects of repetitive hyperbaric oxygen treatment in patients with acute cerebral infarction: a pilot study.

The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This prospective study assessed the efficacy and safety of HBOT as adjuvant treatment on 46 acute ischemic stroke in patients who did not receive thrombolytic therapy. The HBOT group (n = 16) received conventional medical treatment with 10 sessions of adjunctive HBOT within 3-5 days after stroke onset, while the control group (n = 30) received the same treatment but without HBOT. Early (around two weeks after onset) and late (one month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. The baseline clinical characteristics were similar in both groups. Both early and late outcomes of the HBOT group showed significant difference (P ≤ 0.001). In the control group, there was only significant difference in early outcome (P = 0.004). For early efficacy, there was no difference when comparing changes of NIHSS scores between the two groups (P = 0.140) but there was statistically significant difference when comparing changes of NIHSS scores at one month (P ≤ 0.001). The HBOT used in this study may be effective for patients with acute ischemic stroke and is a safe and harmless adjunctive treatment.

Improvement of clinical outcome and cerebral perfusion in a patient of atherosclerotic cerebral infarction after repetitive hyperbaric oxygen treatment--a case report and literature review.

This is a case report of hyperbaric oxygen therapy (HBO2T) for ischemic stroke. HBO2T should be the potential or additional treatment (with thrombolytic therapy) for ischemic stroke according to the preclinical and clinical studies. Hereby, we present a 56-year-old Chinese man with vascular risk factors. He had an acute ischemic stroke on the left corona radiata, with right hemiparesis and dysarthria resulting from atherosclerosis. The patient could not get thrombolytic treatment because the time to ER was in excess of five hours. He experienced great improvement after the general course of HBO2T; this was evaluated with standard rating scales for stroke research and cerebral perfusion images, including brain-computed tomography perfusion (CTP) and single-photon emission computed tomography (SPECT). Although few clinical trials showed a negative result, we suggest that further trials on HBO2T are still needed. Meanwhile, we emphasize the importance of HBO2T protocol and the selection of a suitable patient, which may influence the outcome.

Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells.

Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol.

Amyloid P component as a plasma marker for Parkinson's disease identified by a proteomic approach.

OBJECTIVES: Parkinson's disease (PD) ranks the second among the neurodegenerative disorders. Proteins involved in Parkinson's disease (PD) have been investigated but none as the diagnostic markers in blood. DESIGN AND METHODS: In this study, we applied a proteomic strategy, by utilizing two-dimensional electrophoresis and mass spectrometry, to analyze two sample pools of plasma from the healthy individuals and PD subjects. RESULTS: IgGκL and human serum amyloid P component (SAP) were found differentially expressed between these pools. SAP level increased by approximately 5-fold in PD samples, and the ELISA procedure revealed a significant (P<0.001) increase in SAP concentration (65.9 ± 18.7µg/mL) in the plasma of PD subjects (healthy individuals, 35.0 ± 12.5µg/mL), with sensitivity of 94.1% and specificity of 87.5%. CONCLUSION: Our results indicated a potential feasibility of plasma SAP as a marker to approach PD.