OBJECTIVETo investigate the effect of curcumin on oligomer formation and mitochondrial ATP-sensitive potassium channels (mitoKATP) induced by overexpression or mutation of α-synuclein.

METHODSRecombinant plasmids α-synuclein-pEGFP-A53T and α-synuclein-pEGFP-WT were transfected into PC12 cells by lipofectamin method, and intervened by application of curcumin (20 μmol/L) and 5-hydroxydecanoate (5-HD). Oligomer formation in the cultured cells was identified by Western blotting and Dot blotting. Cytotoxicity and apoptosis of the PC12 cells were measured by lactate dehydrogenase (LDH) and JC-1 assays. mitoKATP were identified by Western blotting and whole cell patch clamp.

RESULTSCurcumin has significantly reduced the oligomer formation induced by overexpression or mutation of α-synuclein in the cultured cells. LDH has decreased by 36.3% and 23.5%, and red/green fluorescence ratio of JC-1 was increased respectively by 48.46% and 50.33% after application of curcumin (P<0.05). Protein expression of Kir6.2 has decreased and mitoKATP channel current has significantly increased (P<0.05).

CONCLUSIONCurcumin can inhibit α-synuclein gene overexpression or mutation induced α-synuclein oligomers formation. It may block apoptosis induced by wild-type overexpression or mutation of α-synuclein. By stabilizing mitochondrial membrane potential. Opening of mitoKATP channel may have been the initiating protective mechanism of apoptosis induced by wild-type overexpression or mutation of α-synuclein. Curcumin may antagonize above cytotoxicity through further opening the mitoKATP channel.

Animals ; Apoptosis ; drug effects ; Cell Line ; Curcumin ; pharmacology ; Humans ; KATP Channels ; chemistry ; genetics ; metabolism ; Mitochondria ; drug effects ; genetics ; metabolism ; Mutation ; drug effects ; PC12 Cells ; Parkinson Disease ; drug therapy ; genetics ; metabolism ; physiopathology ; Rats ; alpha-Synuclein ; genetics

Objective To survey the current status of professional value among health workers in grass-roots medical institutions of Wenzhou city and to analyze the influencing factors.Methods A survey on professional value was conducted from October to December 2017 among health workers from 14 primary medical institutions in 4 urban districts of Wenzhou City selected by stratified random sampling method.The self-designed questionnaires were used for the survey.A total of 350 questionnaires were distributed and 331 were returned,of which 302 were valid.The status and influencing factors of professional value were analyzed.Results The overall score of professional value was (96.66 ± 14.94).The univariate analysis showed that the professional value scores were associated with educational level (F=3.851),income(F=2.660),professional title(F=8.030),position(F=11.658) and specialty (F=4.667) of the health workers(all P＜0.05).The multivariate analysis showed that the gender(male:OR=0.53,95％ CI:-1.077--0.192,P=0.005),educational level (high school and below:OR=3.06,95％ CI:0.007-2.233,P=0.049),income (2 000-4 000 Yuan:OR=0.07,95％ CI:-4.783-0.627,P=0.011),professional title (no title:OR=0.27,95％CI:-2.397--0.232,P=0.017;Junior title:OR=0.31,95％CI:-2.197--0.153),P--0.024;intermediate title:OR=0.23,95％ CI:-2.533--0.366,P--0.009),position (doctor:OR=0.13,95％ CI:-3.235--0.815,P=0.001;nurse:OR=0.20,95％ CI:-2.883--0.368,P=0.011;technician:OR=0.15,95％ CI:-3.076--0.723,P=0.002)were influencing factors of professional value(all P＜0.05).Conclusion The professional values among health workers in Wenzhou grass-roots medical institutions are relatively low.The male gender,low educational level,low income,low professional title or no title and positions are influencing factors of professional value.

Objective:To explore the technical feasibility of CT feature tracking (CT-FT) technique in evaluating left ventricular myocardial strain and evaluate the change of myocardial strain in patients with coronary heart disease.Methods:Eighty-one patients with coronary heart disease (lesion group) and 33 patients with normal coronary artery (control group) matched with age and sex were collected retrospectively from the Second Affiliated Hospital of Nanchang University from April 2019 to October 2020. The lesion group was first divided into single vessel stenosis group (42 cases) and multi vessel stenosis group (39 cases) according to the number of coronary artery stenosis branches, and the global myocardial strains of the left ventricle between the groups were analyzed. Lesion site included the left anterior descending branch (LAD), right coronary artery (RCA) and left circumflex branch (LCX), respectively. According to the degree of vascular stenosis, the lesion groups were divided into normal group, mild stenosis group, moderate stenosis group and severe stenosis group. The segmental myocardial strains of the branch segment of LAD, RCA or LCX were analyzed between groups. All CCTA examinations were performed with retrospective electrocardiogram gating. CVI 42 cardiac postprocessing software was used to obtain myocardial strain parameters, including global peak longitudinal strain (GPLS), global peak circumferential strain (GPCS), global peak radial strain (GPRS), and the segmental myocardial strains of the branch segment of LAD, RCA or LCX. The segmental myocardial strains included the peak longitudinal strain (PLS), peak circumferential strain (PCS) and peak radial strain (PRS). One way ANOVA or Kruskal Wallis H test were used for multi group analysis. Results:With the increased number of coronary artery stenosis branches, the absolute value of GPLS gradually decreased. The GPLS of the control group, single vessel stenosis group and multi vessel stenosis group were -14.1%±2.7%, -11.5%±2.3% and -8.8%±2.0%, respectively. The difference of GPLS between the 3 groups or any 2 groups was statistically significant (all P<0.001). The absolute values of GPRS and GPRS in multi vessel stenosis group were significantly lower than those in control group and single vessel stenosis group (all P<0.001). There was no significant difference in GPRS or GPRS between single vessel stenosis group and control group ( P=0.083, 0.118). And there were significant differences in the segmental myocardial strains of the branch segment of LAD, RCA or LCX among 3 groups ( P<0.001). In severe stenosis group, the absolute values of PRS, PCS and PLS in LAD, RCA or LCX were significantly lower than those in moderate stenosis group, mild stenosis group and normal group (all P<0.05). In the moderate stenosis group, the absolute value of PLS in each branch segment was lower than that of the mild stenosis and normal group (all P<0.05), and there was no significant difference in any 2 other myocardial strain parameters of each branch (all P>0.05). Conclusions:CT-FT technique was feasible to evaluate left ventricular myocardial function. With the increased number or degree of coronary artery stenosis, the global and segmental myocardial strain parameters of left ventricle gradually decreased, and the longitudinal strain was more sensitive.

Objective : To investigate the effect of sinomenine on proliferation and migration of multiple myeloma (MM) cells by regulating STAT3 and NF-κB signaling pathway． Methods : The cultured U266 cells were treated with different concentrations of sinomenine (0，0．5，1，2 mmol / L) ．The control group was added DMSO with 0．5% concentration．CCK-8 assay was used to detect the proliferation of U266 cells．Flow cytometry was used to detect the apoptosis of U266 cells．Western blot assay was used to detect the expression levels of apoptosis-related proteins， STAT3 and NF-κB signaling pathway proteins in the each group. Results : Compared with CON group，the apopto- sis of U266 cells increased after Sinomenine treatment，the proliferation was inhibited ; B lymphoma-2 (Bcl-2) mye- loid and cell leukemia-1 (Mcl-1) expression level decreased ; activated Caspase-3 (cleaved Caspase-3) and PARP (Cleaved Caspase-3) expression levels increased ; the activity of STAT3 and NF-κB signaling pathway decreased. Conclusion Sinomenine can down-regulate the activity of STAT3 and NF-κB signaling pathway，promote the apop- tosis of U266 cells and inhibit the proliferation of U266 cells.