Role of BraRGL1 in regulation of Brassica rapa bolting and flowering

Gibberellin(GA)plays a major role in controlling Brassica rapa stalk development.As an essential negative regulator of GA signal transduction,DELLA proteins may exert significant effects on stalk development.However,the regulatory mechanisms underlying this regulation remain unclear.In this study,we report highly efficient and inheritable mutagenesis using the CRISPR/Cas9 gene editing system in BraPDS(phytoene desaturase)and BraRGL1(key DELLA protein)genes.We observed a loss-of-function mutation in BraRGL1 due to two amino acids in GRAS domain.The flower bud differentiation and bolting time of BraRGL1 mutants were significantly advanced.The expression of GA-regulatory protein(BraGASA6),flowering related genes(BraSOC1,BraLFY),expansion protein(BraEXPA11)and xyloglucan endotransferase(BraXTH3)genes was also significantly upregulated in these mutants.BraRGL1-overexpressing plants displayed the contrasting phenotypes.BraRGL1 mutants were more sensitive to GA signaling.BraRGL1 interacted with BraSOC1,and the interaction intensity decreased after GA3 treatment.In addition,BraRGL1 inhibited the transcription-activation ability of BraSOC1 for BraXTH3 and BraLFY genes,but the presence of GA3 enhanced the activation ability of BraSOC1,suggesting that the BraRGL1-BraSOC1 module regulates bolting and flowering of B.rapa through GA signal transduction.Thus,we hypothesized that BraRGL1 is degraded,and BraSOC1 is released in the presence of GA3,which promotes the expression of BraXTH3 and BraLFY,thereby inducing stalk development in B.rapa.Further,the BraRGL1-M mutant promoted the flower bud differentiation without affecting the stalk quality.Thus,BraRGL1 can serve as a valuable target for the molecular breeding of early maturing varieties.

Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

Resveratrol possesses beneficial biological effects, which include anti-oxidant, anti-inflammatory and anti-carcinogenic properties. Recently, resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson＇s disease, cerebral ischemia and Alzheimer＇s disease. However, its effects on vascular dementia remain unclear. The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion. At 8-12 weeks after model induction, rats were intragastrically administered 25 mg/kg resveratrol daily. Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze, and pro- longed the time spent percentage and swimming distance percentage in the target quadrant during the probe test, indicating that resveratrol improved learning and memory ability in vascular dementia rats. Further experiments found that resveratrol decreased malonyldialdehyde levels, and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats. These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.

Bone marrow-derived mesenchymal stem cells increase dopamine synthesis in the injured striatum

Previous studies showed that tyrosine hydroxylase or neurturin gene-modified cells transplanted into rats with Parkinson＇s disease significantly improved behavior and increased striatal dopamine content. In the present study, we transplanted tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells into the damaged striatum of Parkinson＇s disease model rats. Several weeks after cell transplantation, in addition to an improvement of motor function tyrosine hydroxylase and neurturin proteins were up-regulated in the injured striatum, and importantly, levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid increased significantly. Furthermore, the density of the D2 dopamine receptor in the postsynaptic membranes of dopaminergic neurons was decreased. These results indicate that transplantation of tyrosine hydroxylase and neurturin gene-modified bone marrow-derived mesenchymal stem cells increases dopamine synthesis and significantly improves the behavior of rats with Parkinson＇s disease.

Brain-derived neurotrophic factor prevents beta-amyloid-induced apoptosis of pheochromocytoma cells by regulating Bax/Bcl-2 expression

Brain-derived neurotrophic factor was utilized in the present study to treat cell injury models induced by aggregated β-amyloid（25 35）. Methylthiazolyldiphenyl-tetrazolium bromide assay and western blot analysis showed that brain-derived neurotrophic factor provided neuroprotection against cellular apoptosis by suppressing the decline in β-amyloid（25 35）-induced cell activity and the increasing ratio of Bax/Bcl-2. After treating pheochromocytoma cells with tyrosine kinase receptor B receptor inhibitor K252a, brain-derived neurotrophic factor reverses the above- mentioned changes. The experimental findings suggested that brain-derived neurotrophic factor prevented β-amyloid peptide-induced cellular apoptosis by modulating Bax/Bcl-2 expression, and this effect was associated with binding to the specific tyrosine kinase receptor B receptor.

Mechanisms regulating cerebral hypoperfusion in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia. As the most common type of inherited CSVD, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the NOTCH3 gene mutation which leads to Notch3 ectodomain deposition and extracellular matrix aggregation around the small vessels. It further causes smooth muscle cell degeneration and small vessel arteriopathy in the central nervous system. Compromised cerebral blood flow occurs in the early stage of CADASIL and is associated with white matter hyperintensity, the typical neuroimaging pathology of CADASIL. This suggests that cerebral hypoperfusion may play an important role in the pathogenesis of CADASIL. However, the mechanistic linkage between NOTCH3 mutation and cerebral hypoperfusion remains unknown. Therefore, in this mini-review, it examines the cellular and molecular mechanisms contributing to cerebral hypoperfusion in CADASIL.

Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL)is an early-onset inherited small vessel disease.Decreased cerebral blood flow(CBF)may contribute to white matter hyperintensity(WMH)severity in CADASIL,but more evidence is needed to support this hypothesis.This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls.We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions:WMH,normal-appearing white matter(NAWM),gray matter(GM),and global brain.We analyzed the relationship between CBF of each region and the WMH volume.Compared with the control group,CBF was significantly decreased in all four regions in the CADASIL group.Lower CBF in these regions was correlated with higher WMH volume in CADASIL.CBF in the NAWM,GM and global regions was positively correlated with that in WMH region.However,after correction tests,only CBF in the WMH region but not in NAWM,GM and global regions was associated with WMH volume.Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.

Brain-derived neurotrophic factor protects PC12 cells from beta-amyloid-induced neurotoxicity through the tropomyosin-related kinase B receptor pathway

The present study utilized beta amyloid （Aβ）-induced cell apoptosis in PC12 cells as a cell model of Alzheimer＇s disease to investigate the interaction between brain-derived neurotrophic factor （BDNF） and the tropomyosin-related kinase B receptor. Results showed that Aβ（25-35） can reduce survival of PC12 cells and increase cleaved caspase-3 expression in PC12 cells. However, BDNF inhibited Aβ（25-35）-induced cytotoxicity and cleaved casapase-3 expression. Interestingly, pretreatment with the tropomyosin-related kinase receptor inhibitor K252a for 20 minutes prior to BDNF blocked the neuroprotective effect of BDNF on PC12 cells.

A novel aptasensor strategy for protein detection based on G-quadruplex and exonuclease Ⅲ-aided recycling amplification

The detection of biomarkers is of great significance in the diagnosis of numerous diseases,especially cancer.Herein,we developed a sensitive and universal fluorescent aptasensor strategy based on magnetic beads,DNA G-quadruplex,and exonuclease Ⅲ(Exo Ⅲ).In the presence of a target protein,a label-free single strand DNA(ssDNA)hybridized with the aptamer was released as a trigger DNA due to specific recognition between the aptamer and target.Subsequently,ssDNA initiates the ExoⅢ-aided recycling to amplify the fluorescence signal,which was caused by N-methylmesoporphyrin IX(NMM)insertion into the G-quadruplex structure.This proposed strategy combines the excellent specificity between the aptamer and target,high sensitivity of the fluorescence signal by G-quadruplex and ExoⅢ-aided recycling amplification.We selected(50-1200 nmol/L)MUC1,a common tumor biomarker,as the proof-of-concept target to test the specificity of our aptasenso r.Results reveal that the sensor sensitively and selectively detected the target protein with limits of detection(LODs)of 3.68 and 12.83 nmol/L in buffer solution and 10%serum system,respectively.The strategy can be easily applied to other targets by simply substituting corresponding aptamers and has great potential in the diagnosis and monitoring of several diseases.