Parkinson's disease (PD) is a progressively debilitating neurodegenerative condition that leads to motor and cognitive dysfunction. At present, clinical treatment can only improve symptoms, but cannot effectively protect dopaminergic neurons. Several reports have demonstrated that human umbilical cord mesenchymal stem cells (hucMSCs) afford neuroprotection, while their application is limited because of their uncontrollable differentiation and other reasons. Stem cells communicate with cells through secreted exosomes (Exos), the present study aimed to explore whether Exos secreted by hucMSCs could function instead of hucMSCs. hucMSCs were successfully isolated and characterized, and shown to contribute to 6-hydroxydopamine (6-OHDA)-stimulated SH-SY5Y cell proliferation; hucMSC-derived Exos were also involved in this process. The Exos were purified and identified, and then labeled with PKH 26, it was found that the Exos could be efficiently taken up by SH-SY5Y cells after 12 h of incubation. Pretreatment with Exos promoted 6-OHDA-stimulated SH-SY5Y cells to proliferate and inhibited apoptosis by inducing autophagy. Furthermore, Exos reached the substantia nigra through the blood-brain barrier (BBB) in vivo, relieved apomorphine-induced asymmetric rotation, reduced substantia nigra dopaminergic neuron loss and apoptosis, and upregulated the level of dopamine in the striatum. These results demonstrate that hucMSCs-Exos have a treatment capability for PD and can traverse the BBB, indicating their potential for the effective treatment of PD.
PurposeThis study aims to investigate the prognostic value of pretreatment C-reactive protein/albumin ratio (CAR) in human malignancies by an updated meta-analysis.MethodsPubMed, Web of Science, Cochrane Library and Wanfang databases were searched. Pooled hazard ratios (HRs) and odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were used as effective values.ResultsA total of 25 studies with 12,097 patients were included in this meta-analysis. Pooled results showed that high pretreatment CAR was associated with poor overall survival (OS) (HR =1.99, 95% CI: 1.65–2.40, P=0.000) and poor disease-free survival (HR =1.55, 95% CI: 1.34–1.79, P=0.000). In addition, high pretreatment CAR was associated with increased 5-year mortality (OR =2.74, 95% CI: 2.11–3.55, P=0.000). Moreover, subgroup analysis demonstrated that high CAR was associated with poor OS despite variations in publication year, country, sample size, CAR cut-off value and treatment. However, high CAR was associated with poor OS in human malignancies except colorectal cancer (HR =1.64, 95% CI: 0.96–2.80, P=0.069).ConclusionHigh pretreatment CAR indicates poor prognosis in human malignancies except colorectal cancer. Thus, pretreatment CAR serves as a prognostic marker in human malignancies and could be used in the evaluation of prognosis in clinical work.
Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by amyloid plaque accumulations, intracellular tangles and neuronal loss in certain brain regions. It has been shown that a disturbance of normal iron metabolism contributes to the pathophysiology of AD. However, the mechanism underlying abnormal iron load in the brain of AD patients is unclear. The frontal cortex, an important brain structure for executive function, is one of the regions affected by AD. We investigated the beneficial effects of active compounds of Epimedium, Astragaoside and Puerarin on iron metabolism in the frontal cortex of six-month-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse, a model of AD. Treatment with the active compounds reduced cognitive and memory deficits and damaged cell ultrastructure in APP/PS1 mice. These beneficial effects were associated with changes in expression levels of iron metabolism proteins in the frontal cortex, including divalent metal transporter with iron response element (DMT1-with IRE), divalent metal transporter without iron response element (DMT1-without IRE), transferrin (TF) and transferring receptor 1 (TfR1); three release proteins including the exporter ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (HEPH), one increased storage iron protein ferritin and one iron regulating hormone hepcidin. These findings suggest that the active compounds improve cognition and memory in brain neurodegenerative disorders and these beneficial effects are associated with reduced impairment of iron metabolism. This study may provide a new strategy for developing novel drugs to treat AD.
Parkinson’s disease (PD) is a progressive neurological disorder characterized by loss of neurons that synthesize dopamine, and subsequent impaired movement. Umbilical cord mesenchymal stem cells (UC-MSCs) exerted neuroprotection effects in a rodent model of PD. However, the mechanism underlying UC-MSC-generated neuroprotection was not fully elucidated. In the present study, we found that intranasal administration of UC-MSCs significantly alleviated locomotor deficits and rescued dopaminergic neurons by inhibiting neuroinflammation in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, a toxic agent which selectively destroys nigrostriatal neurons but does not affect dopaminergic neurons elsewhere). Furthermore, UC-MSC treatment altered gut microbiota composition characterized by decreased phylum Proteobacteria, class Gammaproteobacteria, family Enterobacteriaceae, and genus Escherichia-Shigella. In addition, the neurotransmitter dopamine in the striatum and 5-hydroxytryptamine in the colon were also modulated by UC-MSCs. Meanwhile, UC-MSCs significantly maintained intestinal goblet cells, which secrete mucus as a mechanical barrier against pathogens. Furthermore, UC-MSCs alleviate the level of TNF-α and IL-6 as well as the conversion of NF-κB expression in the colon, indicating that inflammatory responses were blocked by UC-MSCs. PICRUSt showed that some pathways including bacterial invasion of epithelial cells, fluorobenzoate degradation, and pathogenic Escherichia coli infection were significantly reversed by UC-MSCs. These data suggest that the beneficial effects were detected following UC-MSC intranasal transplantation in MPTP-treated mice. There is a possible neuroprotective role of UC-MSCs in MPTP-induced PD mice by cross talk between the brain and gut.
Progress was evaluated after four cycles of recurrent selection among S o plants of Glycine max (L .) Merr . in which selection was either for maturity (MAT) or seed protein (PRO) . The two populations, MAT and PRO, were developed from an initial population that was a combination of a line with 48 .4% seed protein and two F2 populations segregating for male sterility . Intermating was facilitated by genetic male-sterility and the selection intensity was 20% in each cycle of the two populations . Selection for early maturity advanced the average maturity a, significant 2 .7 ± 0 .34 days cycle-' and reduced seed yield a non-significant 9 .1 ± 2 .95 g plant-1 cycle -'. Selection increased mean seed protein a significant 0 .8 ± 0 .15 percentage points cycle -' and decreased percent seed oil a non-significant 0 .5 ± 0 .17 percentage points cycle -'. Correlation coefficients between seed protein and seed yield varied from 0 .18 to -0.21 in the four cycles indicating plants with favorable combinations of seed yield and seed protein could be identified . Selection in these two populations would be effective for early maturity and for increased seed protein .
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