Quality Standard of Rutin in the Leaves of Thespesia populnea

[Objectives]To establish a quality standard method for detecting rutin in leaves of Thespesia populnea.[Methods]The leaves of T.populnea as a reagent,the rutin in the leaves of T.populnea was extracted by alcohol extraction,and quantitatively analyzed by high performance liquid chromatography(HPLC).[Results]In the range of 0.21-3.36μg,the peak area A of rutin in the leaves of T.populnea had a good linear relationship with its injection volume m.A=1561.6 m-6.893,and the correlation coefficient r=1.0000.The method was applied to the determination of rutin ethyl acetate extract in the leaves of T.populnea,the average recovery rate was 101.75%,and the RSD was 1.32%.[Conclusions]This method is simple and feasible,the results are accurate,the repeatability is good,and the separation effect is good.It is expected to provide a scientific idea for the determination of rutin in the leaves of T.populnea.

E674Q(Shanghai APP mutant),a novel amyloid precursor protein mutation,in familial late-onset Alzheimer's disease

Identified as the pathogenic genes of Alzheimer's disease(AD),APP,PSEN1,and PSEN2 mainly lead to early-onset AD,whose course is more aggressive,and atypical symptoms are more common than sporadic AD.Here,a novel missense mutation,APP E674Q(also named“Shanghai APP”),was detected in a Chinese index patient with typical late-onset AD(LOAD)who developed memory decline in his mid-70s.The results from neuroimaging were consistent with AD,where widespread amyloidβdeposition was demonstrated in 18 F-florbetapir Positron Emission Tomography(PET).APP E674Q is close to theβ-secretase cleavage site and the well-studied Swedish APP mutation(KM670/671NL),which was predicted to be pathogenic in silico.Molecular dynamics simulation indicated that the E674Q mutation resulted in a rearrangement of the interaction mode between APP and BACE1 and that the E674Q mutation was more prone to cleavage by BACE1.The in vitro results suggested that the E674Q mutation was pathogenic by facilitating the BACE1-mediated processing of APP and the production of Aβ.Furthermore,we applied an adeno-associated virus(AAV)-mediated transfer of the human E674Q mutant APP gene to the hippocampi of two-month-old C57Bl/6 J mice.AAV-E674Q-injected mice exhibited impaired learning behavior and increased pathological burden in the brain,implying that the E674Q mutation had a pathogenicity that bore a comparison with the classical Swedish mutation.Collectively,we report a strong amyloidogenic effect of the E674Q substitution in AD.To our knowledge,E674Q is the only pathogenic mutation within the amyloid processing sequence causing LOAD.

HDAC4 inhibits the transcriptional activation of mda-7/IL-24 induced by Sp1

Melanoma differentiation-associated gene/interleukin-24(mda-7/IL-24)is a cytokine that can activate monocytes and T helper 2 cells.The expression of mda-7/IL-24 gradually fades with the progression of melanoma,and it is undetectable at the metastatic stage.Ectopic expression of mda-7/IL-24 selectively suppresses growth and induces apoptosis in cancer cells with little harm to normal cells.However,the transcriptional regulation of the mda-7/IL-24 gene has not been extensively studied.In this study,we show that the expression of mda-7/IL-24 was upregulated by the histone deacetylase(HDAC)inhibitors trichostatin A(TSA)and sodium butyrate(NaBu),whereas it was downregulated by HDAC4.We also found that the histone acetylation level and the binding of the transcriptional factor Sp1 to the mad-7 promoter were reduced upon HDAC4 treatment.Moreover,the HDAC inhibitor TSA induced histone hyperacetylation and stimulated Sp1 binding to the mda-7/IL-24 promoter,which in turn enhanced the expression of mda-7/IL-24.Therefore,we conclude that histone acetylation modification plays an important role in the regulation of mda-7/IL-24 and that the transcription factor Sp1 participates in this process.

Corticosteroid-resistant Sweet’s syndrome as the first manifestation of myelodysplastic/myeloproliferative neoplasm-unclassifiable:a case report

A middle-aged man was diagnosed with myelodysplastic/myeloproliferative neoplasm-unclassifiable(MDS/MPN-U),with severe and extensive corticosteroid-resistant Sweet’s syndrome(SS)as the first manifestation,with evidence of clinical manifestations,pathological description,and laboratory evaluation.The skin lesions continued to spread despite treatment with systemic corticosteroids but were successfully treated with intravenous immunoglobulin(IVIG).