Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice

Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress responses.It remains elusive how human somatic stem cell populations might be impacted by SIRT7.Here,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates senescence.Mechanistically,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear periphery.Accordingly,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor.Together,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

Early morning off in patients with Parkinson's disease:a Chinese nationwide study and a 7-question screening scale

Background:Early morning off(EMO)is a common feature of Parkinson's disease(PD).This study aimed to characterize its clinical features and develop a convenient and pragmatic self-assessment instrument in a Chinese nationwide population.Methods:This study was conducted on 942 PD patients admitted to 55 clinic centers for movement disorders between June 2018 and May 2019 in China.Stepwise logistic regression analyses were performed to determine potential risk factors and the most predictive symptoms of EMO,as well as whether EMO was an independent risk factor of functional dependency in daily life.Based on this,a 7-question scale was derived for EMO screening.Diagnostic accuracy of this scale was assessed from the area under the receiver operative characteristic curve(AUROC)and its 95%confidence intervals(CIs).We further calculated sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)for the optimal cutoff point.Results:EMO occurred in 49.2%of PD patients across all disease stages.We identified 7 symptoms most predictive of EMO,including bradykinesia or rigidity,excessive sweating or salivation,ificulty in turning on or getting out of bed,muscle cramp,fatigue or sleepiness,frozen state or freezing gait,and tremor.The resulting 7-item scale was confirmed to be of good discrimination with a relatively large AUROC of 0.83,a relatively high sensitivity of 75.7%,specificity of 77.5%,PPV of 76.5%,and NPV of 76.7%.Nonideal nighttime sleep,long PD duration,advanced H&Y stages,posture instability gait difficulty-dominant or mixed subtypes,and high levodopa dose were independently associated with increased risk of EMO.EMO patients were at 87%higher(OR=1.87,95%C:1.07-3.32)risk of experiencing functional dependency in daily living compared with their counterparts.Conclusions:We demonstrated that EMO is a common feature for PD patients across all disease stages and put forward an EMO-specific screening card of sufficient accuracy and brevity.Meanwhile,we have thrown some light upon potential determinants and negative health effects of EMO.Our findings may exert great impact on improving the awareness,recognition and management of EMO in PD patients.