Impact of Konjac Glucomannan with Different Molecular Weight on Retrogradation Properties of Pea Starch.

The impact of konjac glucomannan (KGM) with different molecular weight (Mw) on the retrogradation properties of pea starch, such as color, viscoelasticity, gel strength, water holding capacity (WHC), moisture distribution and crystallinity, was investigated. At the same time as the Mw of KGM decreased, the lightness, elastic modulus, gel strength, water freedom and crystallinity of pea starch showed an increasing trend, whereas the viscosity modulus and WHC showed a decreasing trend. At one day of storage, compared with single pea starch, KGM with low Mw made gel strength increase from 40 g to 45 g, WHC decrease from 82% to 65% and crystallinity increase from 21.3% to 24.0%. Therefore, KGM with low Mw could promote retrogradation of pea starch in the short-term. At 7 days or even 14 days of storage, KGM with medium-high Mw had smaller indices than those of pure pea starch, including the lightness, storage modulus, gel strength, water freedom and crystallinity. This indicated that KGM with medium-high Mw could inhibit the long-term retrogradation of starch. The larger the Mw of KGM, the more noticeable the inhibition effect.

Effects of Konjac Glucomannan on Retrogradation of Amylose.

The effect of konjac glucomannan (KGM) on the retrogradation of amylose was explored during storage. The color, rheological properties, texture, water-holding capacity (WHC), low-field nuclear magnetic resonance (LF-NMR), and X-ray diffraction (XRD) were investigated. Results of color and rheological measurements showed that with the increasing amount of KGM, the L value of the system decreased, but the elastic modulus, viscous modulus, and tangent value of loss angle increased. The textural result presented that KGM obviously inhibited the growth rate of gel strength of amylose. Results from WHC and XRD suggested after 14 days of storage, when the concentration of KGM increased from zero to 0.3% in the mixture, the WHC grew from 80% to 95% and the crystallinity degree declined from 35.3% to 25.6%. The LF-NMR result revealed that KGM limited the conversion of free water to bound water in the system. In general, a small amount of KGM in a mixed system could inhibit the short-term and long-term retrogradation of amylose. This research could provide a theoretical reference for the influence of hydrophilic colloids on the retrogradation of starch, and it could also provide support for the processing and production of starch-based food.

Enhanced autophagy interacting proteins negatively correlated with the activation of apoptosis-related caspase family proteins after focal ischemic stroke of young rats.

BACKGROUND: Neuronal injury induced in young rats by cerebral ischemia reperfusion (CIR) is known to differ substantially from that in adult rats. In the present study, we investigated the specific differences in neuronal injury induced by focal CIR between young and adult rats. RESULTS: 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining revealed a gradual increase in the infarct volume of both young and adult rats in accordance with I/R times and was significantly lower in young rats than in adult rats under the same conditions. The number of cells in the cortex showing immunoreactivity for neuronal nuclei (NeuN) gradually decreased in both young and adult rats in accordance with I/R times; these numbers were significantly higher in young rats than in adult rats under the same conditions. Similarly, as the duration of I/R increased, the degree of glial activation in the cortex penumbra region became more severe in both young and adult groups; however, glial activation was significantly lower in the cortex penumbra region of young rats when compared with that in adult rats. In addition, the expression of Beclin-1 was significantly higher in the infarct penumbra of young rats than adult rats and was more frequently co-expressed with neurons. The levels of autophagy-related proteins increased significantly in the penumbra region after I/R in both young and adult groups, this increase was more pronounced in young rats than in adult rats. Following CIR, analysis revealed significantly lower levels of pro-apoptosis-related factors and significantly higher levels of anti-apoptosis-related proteins in the young rats than in adult rats. CONCLUSIONS: Collectively, the present results suggest that the the reduced levels of neuronal death after CIR in young rats were closely related to enhanced levels of autophagy and reduced levels of pro-apoptosis in neurons.

Targeting the Erk1/2 and autophagy signaling easily improved the neurobalst differentiation and cognitive function after young transient forebrain ischemia compared to old gerbils.

The hippocampal neurogenesis occurs constitutively throughout adulthood in mammalian species, but declines with age. In this study, we overtly found that the neuroblast proliferation and differentiation in the subgranular zone and the maturation into fully functional and integrated neurons in the granule-cell layer in young gerbils following cerebral ischemia/reperfusion was much more than those in old gerbils. The neurological function and cognitive and memory-function rehabilitation in the young gerbils improved faster than those in the old one. These results demonstrated that, during long term after cerebral ischemia/reperfusion, the ability of neurogenesis and recovery of nerve function in young animals were significantly higher than that in the old animals. We found that, after 14- and 28-day cerebral ischemia/reperfusion, the phosphorylation of MEK1/2, ERK1/2, p90RSK, and MSK1/2 protein levels in the hippocampus of young gerbils was significantly much higher than that of old gerbils. The levels of autophagy-related proteins, including Beclin-1, Atg3, Atg5, and LC3 in the hippocampus were effectively maintained and elevated at 28 days after cerebral ischemia/reperfusion in the young gerbils compared with those in the old gerbils. These results indicated that an increase or maintenance of the phosphorylation of ERK1/2 signal pathway and autophagy-related proteins was closely associated with the neuroblast proliferation and differentiation and the process of maturation into neurons. Further, we proved that neuroblast proliferation and differentiation in the dentate gyrus and cognitive function were significantly reversed in young cerebral ischemic gerbils by administering the ERK inhibitor (U0126) and autophagy inhibitor (3MA). In brief, following experimental young ischemic stroke, the long-term promotion of the neurogenesis in the young gerbil's hippocampal dentate gyrus by upregulating the phosphorylation of ERK signaling pathway and maintaining autophagy-related protein levels, it overtly improved the neurological function and cognitive and memory function.

Oxymatrine Attenuates Dopaminergic Neuronal Damage and Microglia-Mediated Neuroinflammation Through Cathepsin D-Dependent HMGB1/TLR4/NF-κB Pathway in Parkinson's Disease.

Oxymatrine (OMT), a natural quinoxaline alkaloid extracted from the root of Sophora flavescens, presents amounts of pharmacological properties including immunomodulation, anti-inflammation, anti-oxidation, and anti-virus. Recent studies tend to focus on its effects on neuroinflammation and neuroprotection in Parkinson's disease (PD) due to its profound anti-inflammatory effect. In this study, the neuroprotective and anti-neuroinflammatory effects of OMT were investigated in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-stimulated mice and 1-methyl-4-phenylpyridinium (MPP+)-induced mice primary microglia. Additionally, mice primary neuron-microglia co-cultures and primary microglia infected with Cathepsin D (CathD)-overexpressed lentivirus were used to clarify whether the neuroprotective effect of OMT was through a CathD-dependent pathway. Results showed that OMT dose-dependently alleviated MPTP-induced motor deficits and conferred significant dopamine (DA) neuroprotection against MPTP/MPP+-induced neurotoxicity. In addition, OMT inhibited MPTP/MPP+-induced microglia activation and the pro-inflammatory cytokines release. Further, OMT down-regulated the expression of CathD, and inhibited the activation of the HMGB1/TLR4 signaling pathway as well as the nuclear translocation of NF-κB both in vivo and in vitro. It is worth noting that overexpression of CathD reversed OMT-targeted inhibition of HMGB1/TLR4/NF-κB signaling and OMT-produced neuroprotection in reconstituted neuron-microglia co-cultures. Our findings indicated that OMT conferred DA neuroprotection and attenuated microglial-mediated neuroinflammation through CathD-dependent inhibition of HMGB1/TLR4/NF-κB signaling pathway. Our study supports a potential role for OMT in ameliorating PD, and proposes that OMT may be useful in the treatment of PD.

Downregulation of miR-21 suppresses 1-methyl-4-phenylpyridinium-induced neuronal damage in MES23.5 cells.

Accumulating evidence suggests that overproduction of oxidative stress, increases neuroinflammation and activates apoptosis. These two processes are associated with the development of Parkinson's disease (PD). The present study aimed to investigate the role of miR-21 in the development of PD. 1-Methyl-4-phenylpyridinium (MPP+) was used to induce a PD-like model in MES23.5 cells. The results of the reverse transcription-quantitative PCR assays indicated that miR-21 levels were markedly increased in MES23.5 cells following MPP+ treatment. Furthermore, MES23.5 cells were transfected with miR-21 inhibitor, mimics and/or relevant negative control, following MPP+ administration. The results of the functional assays revealed that downregulation of miR-21 significantly attenuated the induction of cell apoptosis and reactive oxygen species (ROS) production, while it enhanced the survival of MPP+-induced MES23.5 cells. Furthermore, downregulation of miR-21 increased the expression levels of tyrosine hydroxylase, whereas suppression of miR-21 inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, IL-1ß and tumor necrosis factor-α] in MES23.5 cells. Western blot analysis further indicated that the Bcl-2/Bax protein expression ratio was significantly increased and double luciferase assay analysis confirmed that Bcl-2 was a direct target of miR-21. Taken collectively, the data demonstrated that downregulation of miR-21 protected cells from MPP+-mediated cytotoxicity by the inhibition of apoptosis induction, the reduction of the inflammatory response and the suppression of ROS production. The present findings may provide novel approaches for PD clinical treatment.

Knockdown of cathepsin D protects dopaminergic neurons against neuroinflammation-mediated neurotoxicity through inhibition of NF-κB signalling pathway in Parkinson's disease model.

Parkinson's disease (PD) is a progressive neurodegenerative disorder pathologically characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Chronic neuroinflammation is one of the hallmarks of PD pathophysiology. Cathepsin D (CathD), a soluble aspartic protease, has been reported to play an important role in neurodegenerative diseases such as PD. This research focuses on the role of CathD and the molecular mechanisms involved in the process of neuroinflammation and neurotoxicity. We use 1-methyl-4phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-challenged mice and lipopolysaccharide (LPS)-induced murine microglia BV2 cells as the in vivo and in vitro models, respectively. The effect of CathD on the neuroinflammation, cytotoxicity and the underlying mechanisms associated with NF-κB signalling pathway are investigated. Data showed that MPTP induces motor deficit, inflammation and depletion of dopaminergic neurons in PD model mice. Notably, cathD was overexpressed in the SNpc of MPTP-induced PD mice and was highly expressing in LPS-stimulated primary microglial cells and BV-2 cells. Furthermore, knockdown of CathD with lentiviral transduction inhibited LPS-induced neuroinflammation through inhibition of NF-κB signalling pathway primarily by regulating the NF-κB p65 nuclear translocation both in BV-2 and primary microglial cells. Additionally, knockdown of CathD protected the activated-microglia induced dopaminergic neurons MN9D cells from neurotoxicity as well as apoptosis. Our findings bring a new insight into understanding the complex mechanisms underlying the pathogenesis of PD and provide a novel target to attenuate the excessive neuroinflammatory responses in the treatment of PD.

The prognostic role of RASSF1A promoter methylation in breast cancer: a meta-analysis of published data.

PURPOSE: Epigenetic alterations have been investigated as prognostic indicators in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. We present the results of a meta-analysis of the associations between RASSF1A promoter methylation status and both disease free survival (DFS) and overall survival (OS) in female breast cancer. METHODS: Eligible studies were identified through searching the PubMed, Web of Science and Embase databases. Studies were pooled and summary hazard ratios (HR) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also carried out to evaluate publication bias. RESULTS: A total of 1795 patients from eight studies were included in the meta-analysis. There are eight studies which investigated DFS in 1795 cases. The relative hazard estimates ranged from 1.77-5.64 with a combined HR of 2.75 (95%CI 1.96-3.84). The HR of RASSF1A promoter methylation on DFS adjusted for other potential prognostic factors was 2.54 (95%CI 1.77-3.66). There has been five trials which analyzed the associations of RASSF1A promoter methylation status with OS in 1439 patients. The hazard estimates ranged from 1.21-6.90 with a combined random-effects estimates of 3.47 (95%CI 1.44-8.34). OS reported in multivariate analysis was evaluated in four series comprising 1346 cases and the summarized random-effects HR estimate was 3.35 (95%CI 1.14-9.85). Additionally, no publication bias was detected for both OS and DFS. CONCLUSION: The results of this meta-analysis suggest that RASSF1A promoter hypermethylation confers a higher risk of relapse and a worse survival in patients with breast cancer. Large prospective studies are now needed to establish the clinical utility of RASSF1A promoter methylation.

Early biomarkers for post-stroke cognitive impairment.

The aim of this study was to investigate whether some biomarkers could predict cognitive impairment after stroke. One hundred fifty-two first-ever stroke patients were recruited within 6-72 h after the onset of symptoms. Blood was drawn within 1 h after admission for determining biomarkers. Cognitive function was assayed 2 weeks after stroke. The patients were divided into four groups: stroke, vascular cognitive impairment with no dementia (VCIND), vascular dementia (VaD), and mixed dementia (MD). Forty healthy subjects were used as controls. The results indicated that lower soluble receptor levels for advanced glycation end products (sRAGE) and higher ß-secretase enzyme (BACE1) and neprilysin (NEP) levels were found in the VCIND, VaD, and MD groups. In addition, the percentages of ε3/ε4 genotypes and ε4 alleles in the VCIND, VaD, and MD groups were higher than in the stroke group. Correlation analysis determined that sRAGE, BACE1, and NEP were significantly related to the results of neuropsychological assessments. Logistic regression analysis, however, suggested that only sRAGE and BACE1 changed ahead of cognitive impairment after stroke. In conclusion, only BACE1 and sRAGE, not NEP or APOE genotypes, may be biomarkers diagnosing post-stroke cognitive impairment.