Electron Transport Complex IV ; analysis ; Humans ; Mitochondrial Myopathies ; enzymology ; Staining and Labeling ; Succinate Dehydrogenase ; analysis

[Abstract ] Objective To investigate the molecular mechanism how genistein increased the sensitivity of colon cancer cell to 5-fluorouracil(FU)and promoted colon cancer cell apoptosis.Methods SW480 colon cancer cell line was chosen as experimental object.Genistein 80 μmol/L and 5-FU 30 μg/mL used separated or combined for 48 hours were set as drug experiment group.There were four experiment groups in this study:control group (without any drug),5-FU group,genistein group,5-FU and genistein combined group.The expression of survivin,Bcl-2,p21 ,caspase3 and caspase 9 in the tumor cells of each group at mRNA and protein level was deteced by real-time quantitative polymerase chain reaction (PCR) and Western blotting.The relative expression quantity of genes was determined by comparative threshold method (2 -ΔΔCT )andβ-actin was taken as an internal reference.Semi quantitative analysis was performed for protein relative expression quantity.The DNA combination activity of nuclear factor(NF)-κB of each group was measured by electrophoretic mobility shift assay (EMSA).Single factor analysis of variance was used for mean comparison among multiple groups and LSD test was for mean comparison between two groups.Results The expression of caspase3,caspase 9 and p21 of 5-FU and genistein combination group at mRNA (1 .903±0.122,2.726±0.050 and 2.541 ±0.393)and protein level (0.534±0.077,1 .161 ± 0.172 and 0.463±0.016)were all higher than those of control group (1 .001 ±0.052,1 .000±0.014 and 1 .001 ±0.037;0.080 ±0.043,0.248±0.059 and 0.139 ±0.021 ),genistein group (1 .559 ±0.038, 2.394±0.095 and 1 .686 ±0.061 ;0.335 ±0.052,0.478 ±0.059 and 0.304 ±0.018)and 5-FU group (1 .198±0.063,1 .051 ±0.043 and 1 .399±0.055 ;0.194±0.015 ,0.337 ±0.036 and 0.231 ±0.011 );the expression of survivin of 5-FU and genistein combined group at mRNA and protein level (0.165 ± 0.018 and 0.216±0.014)were all lower than those of control group,genistein group and 5-FU group (1 .001 ±0.033,0.775 ±0.044 and 0.395 ±0.030;0.594±0.079,0.375 ±0.014 and 0.295 ±0.014), and all the differences were statistically significant (gene,F = 802.865 ,52.760,39.992,187.288, 37.435 ;protein,F =10.466,44.483,19.490,200.011 ,45 .238;all P <0.01);the difference was also statistically significant in the expression of caspase3 and p21 of 5-FU group and genistein group compared with those of control group (LSD test,P <0.05 ).The results of EMSA assay showed that the DNA binding activity of NF-κB protein of genistein group (461.64 ±15.41 )and combined group (585.28 ±7.82) significantly decreased compared with that of control group (1 067.97 ±36.01)and 5-FU group (718.83± 23.18,LSD-test,P < 0.05).Conclusions Genistein combined with 5-FU seemed to have synergistic effects on apoptosis of colon cancer cell.The mechanism was that genistein inhibited the DNA binding activity of NF-κB mediated by genistein,further up-regulated caspase 3,caspase 9,p21 and down regulated survivin.Therefore,genistein may provide assistance in colon cancer chemotherapy.

Objective: To investigate the smartphone addiction among college students during the Coronavirus Disease 2019 (COVID-19) pandemic and its association with daily behaviors and mental health,and to provide reference for heath education and psychological counseling for college students. Methods: An observational study using online quyestionnaire was conducted among 10 357 college students of two provincial medical schools in Guangdong and Shanxi Province from February 24th to March 4th in 2020. Participants were investigated on demographic information, smartphone addiction, daily routine, physical activity, weight status, anxiety, and other health information. Logistic regression with inverse probability treatment weighting (IPTW) based on propensity score was used to analyze the association between smartphone addiction with daily behavior and mental health. Results: The prevalence of smartphone addiction was 59.42%. The prevalence of phone addiction was higher in postgraduates, senior undergraduates, students with non-medical major, students living in GuangDong and those without regular exercise habit before vacation(χ 2=47.91，17.78，42.75，138.58，P<0.05). With IPTW, there were significant associations between smartphone addiction and late bedtimes (OR=1.82, 95%CI=1.66-1.98) and wake-up times (OR=1.55, 95%CI=1.44-1.68), more sedentary behaviors (OR=1.21, 95%CI=1.12-1.31), less moderate to vigorous physical activity (OR=1.33, 95%CI=1.22-1.44), anxiety (OR=2.98, 95%CI=2.52-3.40), weight gain(OR=1.27，95%CI=1.17-1.37) and other detrimental daily behavior and feelings. Conclusion High prevalence of smartphone addiction has been observed during the COVID-19 pandemic, with impaired daily behavior and mental health.

OBJECTIVES: Age-related macular degeneration (AMD) is one of the 3 major eye diseases recognized by WHO to prevent blindness, and which is the main cause of irreversible visual impairment in the elderly. This study aims to analyze the disease epidemiological burden, and provide a theoretical foundation for the prevention and control of AMD in China based on the data in global burden of disease (GBD) 2019. METHODS: The prevalent cases/prevalence, disability-adjusted life year (DALYs)/DALY rate of AMD and socio-demographic index (SDI) for global and China were searched from the GBD 2019 database to analyze the epidemiological trend, age-period-gender trend of AMD in China from 1990 to 2019, and to evaluate the relations between the prevalence and SDI. RESULTS: In 2019, the prevalence of AMD in China was at a high level in the world, and the number of prevalent cases were 1.93 times of that in 1990. The prevalence and DALY rates continued to rise. The age trend of AMD in China was high at the middle of the age stages and low at the two ends, and which was higher in the female than in the male. With the increase of SDI, the prevalence of AMD was increased linearly. CONCLUSIONS The disease burden of AMD in China is increased significantly and is positively correlated with the social development from 1990 to 2019. It is of great significance to study the relationship between epidemilolgical data of AMD and social development level for diagnosis treatment and policy of AMD.
Humans ; Male ; Female ; Aged ; Global Burden of Disease ; Quality-Adjusted Life Years ; Prevalence ; Macular Degeneration/epidemiology* ; China/epidemiology*

Objective : To investigate the effect of Arginine Vasopressin (AVP) on the median preoptic glutamatergic (MnPOVglut2 ) neurons and its mechanism． Methods : Brain slices were prepared from male Vglut2-tdTomato mice．MnPOVglut2 neurons expressing red fluorescent protein were located by using fluorescence microscope．Wholecell patch clamp technique was used to observe the effect of AVP on the firing frequency of MnPOVglut2 neurons，the effect of synaptic transmission blockers ( STBs) on the AVP-induced change in the firing frequency of MnPOVglut2 neurons，and the effect of AVP V1a receptor antagonist on the AVP-induced change in the firing frequency of MnPOVglut2 neurons. Results: The mean firing frequency of MnPOVglut2 neurons increased during perfusion with artificial cerebrospinal fluid (ACSF) and AVP compared with that during perfusion with ACSF (P＜0. 01) ，indicating that AVP excited the MnPOVglut2 neurons．The mean firing frequency of MnPOVglut2 neurons still increased during perfusion with ACSF，STBs，and AVP compared with that during perfusion with ACSF and STBs (P＜0. 001) ; moreover，the magnitude of AVP-induced increase in firing frequency didn't change significantly during perfusion with ACSF，STBs，and AVP compared with that during perfusion with ACSF and AVP (P ＞0. 05 ) ，suggesting that AVP excited the MnPOVglut2 neurons directly in a postsynaptic manner．The magnitude of AVP-induced increase in the firing frequency of MnPOVglut2 neurons declined during perfusion with ACSF，STBs，AVP，and V1areceptor antagonist compared with that during perfusion with ACSF，STBs，and AVP (P＜0. 01) ，suggesting that AVP excited MnPOVglut2 neurons directly via V1a receptor． Conclusion AVP can excite MnPOVglut2 neurons via V1areceptor directly in a postsynaptic manner．This study reveals the molecular marker of MnPO neurons which AVP act on.

The well-known insulin-like growth factor 1 (IGF1)/IGF-1 receptor (IGF-1R) signaling pathway is overexpressed in many tumors, and is thus an attractive target for cancer treatment. However, results have often been disappointing due to crosstalk with other signals. Here, we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma (HCC) cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2) activity. In response to ligand binding, IGF-1Rβ is translocated into the ER by β-arrestin2 (β-arr2). Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ. SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβ levels. ER IGF-1Rβ phosphorylates SERCA2 on Tyr⁹⁹⁰ to enhance its activity. Mutation of SERCA2-Tyr⁹⁹⁰ disrupted the interaction of ER IGF-1Rβ with SERCA2, and therefore ER IGF-1Rβ failed to promote SERCA2 activity. The enhancement of SERCA2 activity triggered Ca²⁺_ER perturbation, leading to an increase in autophagy. Thapsigargin blocked the interaction between SERCA2 and ER IGF-1Rβ and therefore SERCA2 activity, resulting in inhibition of HCC growth. In conclusion, the translocation of IGF-1R into the ER triggers Ca²⁺_ER perturbation by enhancing SERCA2 activity through phosphorylating Tyr⁹⁹⁰ in HCC.