Directed evolution of the fusion enzyme for improving astaxanthin biosynthesis in .

The accumulation of the intermediate zeaxanthin and canthaxanthin in the astaxanthin biosynthesis pathway catalyzed by β-carotene hydroxylase () and β-carotene ketolase () decreases the content of the astaxanthin. Here, we exploited directed evolution of the fusion of and for improving astaxanthin biosynthesis in . The results demonstrated that the fusion enzyme of with 2 X GGGGS peptides linker can effectively reduce the accumulation of intermediates and improves the content of astaxanthin.

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.

Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study.

Neuroprotection and CD131/GDNF/AKT Pathway of Carbamylated Erythropoietin in Hypoxic Neurons.

Carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to neuroprotective effects without erythropoiesis. However, little is known about molecular mechanisms behind CEPO-mediated neuroprotection. In primary neurons with oxygen-glucose deprivation (OGD) and mice with hypoxia-reoxygenation, the neuroprotection and possible molecular mechanism of CEPO were performed by immunohistochemistry and immunocytochemistry, Western blot, RT-PCR, and ELISA.

The lack of CD131 and the inhibition of Neuro-2a growth by carbamylated erythropoietin.

Recombinant human erythropoietin (EPO), a glycohormone, is one of the leading biopharmaceutical products, while carbamylated erythropoietin (CEPO), an EPO derivative, is attracting widespread interest due to its neuroprotective effects without erythropoiesis in several cells and animal models. However, exogenous EPO promotes an angiogenic response from tumor cells and is associated with tumor growth, but knowledge of CEPO on tumor growth is lacking. Here we show that CEPO, but not EPO, inhibited Neuro-2a growth and viability.

Histone decacetylase inhibitors prevent mitochondrial fragmentation and elicit early neuroprotection against MPP+.

Background: Parkinson's disease (PD) is a common neurodegenerative disease, characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. Recent investigations have shown that mitochondrial fragmentation, an early event during apoptosis, is implicated in the degeneration of DA neurons in PD, and more importantly, preventing mitochondrial fragmentation could rescue cell death in several PD models. Therefore, mitochondrial dynamics may be a therapeutic target for early intervention in PD.

Novel mutations m.3959G>A and m.3995A>G in mitochondrial gene MT-ND1 associated with MELAS.

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are progressive neurodegenerative disorder associated with polygenetic, maternally inherited mutations in mitochondrial DNA. Approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial tRNA(Leu (UUR)) gene (MT-TL1).

Carbamylated erythropoietin ameliorates hypoxia-induced cognitive and behavioral defects with the generation of choline acetyltransferase-positive neurons.

Carbamylated erythropoietin (CEPO) is attracting widespread interest because of its neuroprotective effects without influencing erythropoiesis. Here we show that CEPO, unlike EPO, does not stimulate erythropoiesis. Both CEPO and EPO inhibit the death/apoptosis of neurons in the hypoxic model of primary neurons and induce neuron proliferation and differentiation in hypoxic mice.

TSPO-specific ligand vinpocetine exerts a neuroprotective effect by suppressing microglial inflammation.

Vinpocetine has long been used for cerebrovascular disorders and cognitive impairment. Based on the evidence that the translocator protein (TSPO, 18 kDa) was expressed in activated microglia, while Vinpocetine was able to bind TSPO, we explored the role of Vinpocetine on microglia treated with lipopolysaccharide (LPS) and oxygen-glucose deprivation (OGD) in vitro. Our results show that both LPS and OGD induced the up-regulation of TSPO expression on BV-2 microglia by RT-PCR, western blot and immunocytochemistry.

HLA-DQA1*03:02/DQB1*03:03:02 is strongly associated with susceptibility to childhood-onset ocular myasthenia gravis in Southern Han Chinese.

Objective: Our aim was to investigate the correlation between onset age, clinical features and HLA-DQA1/DQB1 genetic variability in myasthenia gravis (MG) patients in Southern Han Chinese.

Methods: 205 MG patients and 100 controls were genotyped for HLA-DQA1 and -DQB1 using sequence-based typing (SBT) and analyzed for haplotype frequencies. Anti-acetylcholine receptor (AChR) autoantibodies were measured in all, and muscle-specific tyrosine kinase (MuSK) antibodies were tested in AChR antibody negative patients.

The polymorphism of the ATP-binding cassette transporter 1 gene modulates Alzheimer disease risk in Chinese Han ethnic population.

Background: Recent studies highlight a potential role of cholesterol metabolic disturbance in the pathophysiology of Alzheimer disease (AD). The adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene resides within proximity of linkage peaks on chromosome 9q influence AD and plays a key role in cellular cholesterol efflux in the brain.

Methods: We studied the role of R219K and V825I polymorphisms of ABCA1 in modulating the risk of AD in 321 AD patients and 349 comparisons of Chinese Han.

Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice.

Rho kinase (ROCK) may play an important role in regulating biological events of cells, including proliferation, differentiation and survival/death. Blockade of ROCK promotes axonal regeneration and neuron survival in vivo and in vitro, thereby exhibiting potential clinical applications in spinal cord damage and stroke. Our previous studies have demonstrated that Fasudil, a selective ROCK inhibitor, induced neuroprotection in vitro.

High frequency of Machado-Joseph disease identified in southeastern Chinese kindreds with spinocerebellar ataxia.

Background: Machado-Joseph disease (MJD), caused by a CAG repeat expansion located in exon10 of the ATXN3 gene, is now regarded as one of the most common spinocerebellar ataxia (SCA) in the world. The relative frequency of MJD among SCA has previously been estimated at about 50% in the Chinese population and has been reported to be related to the frequency of large normal alleles in some populations. Taq polymerase has been used for PCR in nearly all studies reported previously.

Therapeutic potential of experimental autoimmune encephalomyelitis by Fasudil, a Rho kinase inhibitor.

The migration of aberrant inflammatory cells into the central nervous system plays an important role in the pathogenesis of demyelinating diseases potentially through the Rho/Rho-kinase (Rock) pathway, but direct evidence from human and animal models remains inadequate. Here we further confirm that Fasudil, a selective Rock inhibitor, has therapeutic potential in a mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The results show that Fasudil decreased the development of EAE in C57BL/6 mice.

Predictors of vascular events after ischemic stroke: the China ischemic stroke registry study.

Background/aims: To measure the risk of vascular event occurrence among postischemic stroke patients in mainland China.

Methods: In this multicenter prospective stroke registry study, we enrolled 1,951 patients diagnosed with acute ischemic stroke. Demographic data, prestroke risk factors, severity of neurological deficits and disability graded on the National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale scores of each patient were measured and recorded.

Fasudil, a Rho kinase inhibitor, drives mobilization of adult neural stem cells after hypoxia/reoxygenation injury in mice.

Rho kinase (ROCK) is important in fundamental processes of cell proliferation and survival. Blockade of ROCK promotes stem cell survival in vitro and axonal regeneration in vivo, exhibiting therapeutic potential such as spinal cord injuries and stroke. Here, we used the model of hypoxia/reoxygenation (H/R) injury to explore the possibility whether Fasudil, a ROCK inhibitor in clinical application for subarachnoid hemorrhage and stroke, mobilizes adult neural stem cells in vivo.

Association of antiplatelet therapy with lower risk of death and recurrent cerebrovascular events after ischemic stroke--results from the China Ischemic Stroke Registry Study.

Background: Evidence of the beneficial effects of antiplatelet therapy after ischemic stroke is currently lacking in China.

Methods And Results: Demographic data, pre-stroke risk factors, severity of neurological deficit, and disability graded by the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) of 1,951 patients were measured and recorded at baseline. Regular follow-up by interview was performed for 12 months post-recruitment.

Granulocyte-colony stimulating factor is involved in low-dose LPS-induced neuroprotection.

Granulocyte-colony stimulating factor (G-CSF) has recently been noted for neuroprotective function. Evidence has been given to indicate that G-CSF is naturally expressed in neurons and directly activates anti-apoptosis pathways. Finding out the agents inducing G-CSF production is of value for understanding the neuroprotection network in central nervous system.

[Quantitative analysis of regional cerebral blood flow in elderly with white matter lesions].

Objective: To observe whether the severity of white matter lesions (WML) is related to ischemia in elderly.

Methods: WML were divided into 2 categories (centrum semiovale and periventricular regions) and four grades (grade 0, grade 1, grade 2 and grade 3) according to the severity of WML showing on the FLAIR sequence of MRI using modified Fazekas scale. The values of regional cerebral blood flow (rCBF) within WML and other brain regions were measured using Xenon contrast CT.

Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF.

Rho-kinases (ROCK) are serine/threonine kinases that play an important role in fundamental processes of cell migration, proliferation and survival. Blockade of ROCK promotes axonal regeneration and neuroprotection, thereby exhibiting therapeutic potentials for clinical application to spinal cord damage and stroke. Here we explored the mechanisms of Fasudil, a ROCK inhibitor, in neuroprotection and neurogenesis by using oxygen-glucose deprivation (OGD) as an in vitro ischemia model.

Carbonic anhydrase III is insufficient in muscles of myasthenia gravis patients.

Myasthenia gravis (MG) is considered as an autoimmune disease mainly mediated by antibodies against acetylcholine receptor. In recent years, other targets related to MG have been the subject of interest. Our previous research found that protein P25 was lower in muscles of MG patients using two-dimensional electrophoresis.

Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China.

Background And Purposes: To evaluate the effects of minimally invasive craniopuncture therapy compared with conservative treatment in treating intracerebral hemorrhage (25-40 ml) in the basal ganglion.

Methods: A multicenter, randomized control clinical trial comprised 465 cases of hemorrhage in the basal ganglion from 42 hospitals in China. Three hundred and seventy-seven patients with hemorrhage were randomly assigned to receive minimally invasive craniopuncture therapy (n=195) or conservative control treatment (n=182).

Cell biology and clinical promise of G-CSF: immunomodulation and neuroprotection.

In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration.

The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen presenting cells in patients with multiple sclerosis and in rats with experimental autoimmune encephalomyelitis.

The possibility to generate and expand tolerogenic dendritic cells (DC) with TGF-beta1 in vitro opens new therapeutic perspectives for the treatment of autoimmune diseases. In the present study, GM-CSF+IL-4 induced the differentiation of DC from adherent peripheral blood mononuclear cells, which had a higher expression of HLA-DR, CD86 and CD1a and the capacity to stimulate T cells. TGF-beta1 alone slightly promoted the generation of antigen presenting cells (APC) with higher expression of CD14, but did not differentiate them into E-cadherin+Langerhans cell (LC)-like DC.

Decrease of CD4(+)CD25(high)Foxp3(+) regulatory T cells and elevation of CD19(+)BAFF-R(+) B cells and soluble ICAM-1 in myasthenia gravis.

Myasthenia gravis (MG) is caused by T-cell-dependent autoantibodies against muscle acetylcholine receptors (AChR) at the neuromuscular junction. Here, we adopted ELISA and flow cytometry techniques to measure the levels of Th1, Th2, Th3 cytokines, inflammatory cytokine and chemokine sICAM-1 and to analyze the phenotypes of CD4(+) and CD8(+) regulatory cells as well as the expression of BAFF-R on CD19(+) B cells in peripheral blood from 75 MG patients and 50 healthy controls. There were no differences in the levels of IL-2, IL-4, IL-10, IL-13, IFN-gamma, TNF-alpha, TGF-beta and sCTLA-4 in both sera and culture supernatants between MG patients and healthy controls.

IL-12/IFN-gamma/NO axis plays critical role in development of Th1-mediated experimental autoimmune encephalomyelitis.

The importance of the IL-12/IFN-gamma/nitric oxide (NO) axis in the pathogenesis of autoimmune diseases remains controversial. In parallel experiments, we explored the role of the IL-12/IFN-gamma/NO axis in the development of MOG 35-55-induced experimental autoimmune encephalomyelitis (EAE) in mice lacking IL-12, IFN-gamma receptor (IFN-gammaR) and inducible nitric oxide synthase (NOS2), respectively. In comparison with wide-type control mice, IL-12-/-, IFN-gammaR-/- and NOS2-/- mice displayed more severe clinical signs of EAE both in remission and at subsequent relapse.