Protective effects of Buyinqianzheng Formula on mitochondrial morphology by PINK1/Parkin pathway in SH-SY5Y cells induced by MPP^(+)

Objective:Buyinqianzheng Formula(BYQZF)is clinically employed in traditional Chinese medicine to treat Parkinson's disease(PD)by improving mitochondrial dysfunction.However,the underlying mechanisms by which BYQZF affects mitochondrial morphology remain unknown.Therefore,we observed the effects of BYQZF on mitochondria from the perspective of the PINK1/Parkin pathway.Methods:Cell survival rates were assessed by Cell Counting Kit-8 assay.Expression levels of PINK1 and Parkin mRNA were examined by qRT-PCR.Protein expression levels of PINK1,PINK1-Ser228,Parkin,Parkin-Ser65,Drp1,and Drp1-Ser637 were examined by western blotting.PINK1,Parkin,and MitoTracker?Red CMXRos(MTR)were stained by triple-labeled immunofluorescence,and observed under laser confocal microscopy.Results:Cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and protein expression levels of PINK1,Parkin,and Drp1-Ser637 were reduced after 1-methyl-4-phenylpyridinium(MPP^(+))intervention.In contrast,Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 increased significantly after MPP^(+) intervention.Treatment with BYQZF increased cell survival rate,mitochondrial form factor,mean length and number of mitochondrial network branches,mitochondrial activity,m RNA expression levels of PINK1 and Parkin,and expression of PINK1,Parkin,and Drp1-Ser637 proteins.Pearson's correlation coefficients between PINK1 and Parkin,and between Parkin and MTR,as well as protein expression levels of PINK1-Ser228,Parkin-Ser65,and Drp1 decreased after BYQZF treatment.Conclusion:These results demonstrate that BYQZF has a protective effect on mitochondrial molecular mechanisms in the PD cell model,and the mechanism is related to the PINK1/Parkin pathway.

Polyketides with potential bioactivities from the mangrove‑derived fungus Talaromyces sp.WHUF0362

Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.

Elucidating Structures of Complex Organic Compounds Using a Machine Learning Model Based on the 13C NMR Chemical Shifts

We present a protocol that combines the support vector machine(SVM)model with accurate 13C chemical shift calculations at the xOPBE/6-311+G(2d,p)level of theory,denoted as SVM-M(i.e.,SVM for magnetic property).We show here that this SVM-M protocol is a versatile tool for identifying the structural and stereochemical assignment of complex organic compounds with high confidence.Of particular significance is that,by utilizing the dual role of the decision values in SVM,the present SVM-M protocol provides an accurate yet efficient solution to simultaneously handle the classification issue(i.e.,“is a given structure correct or incorrect?”)and the comparison-based problem(i.e.,“which structure is more likely to be correct or wrong among several candidate structures?”).A significantly high success rate has been reached(i.e.,∼100%on a set of 760 sample molecules with 1592813C chemical shifts),which makes the SVMM protocol a powerful tool for routine applications in structural and stereochemical assignments,as well as in detecting misassignments,for complex organic compounds,including natural products.