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Objective. To explore the effects of hypertension and dyslipidemia on cognitive function in the elderly. Methods. A dynamic population cohort was established by using prospective cohort study methods. In 2019, a complete cohort was selected from residents aged 65 and above who voluntarily participated in a free physical examination program in a community in Shanghai, serving as the baseline cohort. In 2022, 512 community-dwelling elderly aged 67 to 93 were randomly selected from the same community as the follow-up cohort for the study. The collected date included residents' health records, various physical examination measurements, and Mini-mental State Examination (MMSE) scale scores. Results. Of the 512 cases that were followed up, the valid sample size was reduced to 495 after data cleaning. According to the baseline and follow-up cognitive assessments and changes, the cases were categorized into three cognitive groups: the improvement group, the normal group, and the decline group. The prevalence of hypertension in the decline group was 43.14% higher than that in the improvement group and 24.39% higher than that in the normal group (66.67% in the decline group vs 23.53% in the improvement group, P=0.011; 66.67% in the decline group vs 42.28% in the normal group, P=0.040). Total cholesterol (TC) in the improvement group was lower than that in the normal group [improvement group (4.38±1.04) mmol/L vs normal group (5.11±1.12) mmol/L, P=0.009]. Additionally, TC in the decline group in 2022 was higher than that in 2019 [paired difference (0.46±0.87) mmol/L, 95% CI 0.08-0.84, P=0.021]. LDL-Ch in the improvement group was lower than that in the normal group [improved group (2.51±0.92) mmol/L vs normal group (3.07±1.00) mmol/L, P=0.024], and their HDL-Ch in 2022 was higher than that in 2019 [paired difference (0.16±0.20) mmol/L, 95% CI 0.06-0.26, P=0.005]. The results of multinomial Logistic regression showed: TC in the improved group was lower than that in the normal group [β=4.12, OR=61.64, 95% CI 1.52-2494.07, P=0.029] and the decline group [β=5.88, OR=357.35, 95% CI 4.54-28149.75, P=0.008]; the TAG [β=1.85, OR=6.34, 95% CI 1.05-38.43, P=0.045], LDL-Ch [β=5.61, OR=274.06, 95% CI 3.65-20567.57, P=0.011], and hypertension [β=1.90, OR=6.69, 95% CI 1.53-29.16, P=0.011] in the decline group were higher than those in the improvement group; the age of the decline group was greater than that of the normal group [β=0.08, OR=1.08, 95% CI 1.00-1.16, P=0.041], and the education level was lower than that of the normal group [β=1.22, OR=3.39, 95% CI 1.28-8.94, P=0.014]. Conclusion. Low TC and LDL-Ch and high HDL-Ch are beneficial to cognitive improvement. Conversely, hypertension, high TC, high TAG, high LDLCh, low education level, and advanced ages are risk factors for cognitive decline. [ABSTRACT FROM AUTHOR]

Objective. To reveal the effect of enzyme digestion into cell clumps on protein levels of octamer-binding protein 4 (OCT4) and sex determining region Y-box 2 (SOX2) in the human embryonic stem cells (hESCs) and its possible molecular mechanism. Methods. 1 Western blotting was conducted to detect the protein levels of OCT4 and SOX2 in the hESCs treated by enzyme digestion into cell clumps [Dispase or collagenase type IV (COL4)], enzyme digestion into single cells (Accutase or trypsin), or mechanical scraping dissociation. 2 Ethylene glycol tetraacetic acid (EGTA) was used to destruct hESC-hESC interaction, and protein levels of OCT4 and SOX2 in the hESCs treated with EGTA alone or combined with COL4 were detected by Western blotting. 3 Quantitative proteomics analysis based on mass spectrometry was carried out to identify differentially expressed total proteins and phosphorylated proteins in the hESCs treated with COL4 alone or in combination with EGTA. 4 hESCs were pre-treated with proteasome inhibitor (bortezomib) and lysosome inhibitor (chloroquine), respectively, followed by Western blotting and immunofluorescence staining to measure their effects on COL4-induced down regulation of OCT4 and SOX2. 5 Western blotting analysis was conducted to test the effect of COL4 treatment on cofilin as well as Rac1 inhibitors (EHT1864 and EHop-016) treatment on the protein level of SOX2 in the hESCs. Results. 6 COL4 or Dispase treatment led to protein levels decrease of OCT4 and SOX2, while Accutase, trypsin and mechanical dissociation did not elicit such effect. 7 EGTA rescued OCT4 and SOX2 protein levels decrease indcued by COL4 treatment. 8 Quantitative mass spectrometry and functional enrichment analysis suggested that microtubule, actin filament (F-actin) and lysosome-associated proteins might be related to OCT4 and SOX2 protein levels decline in the suspended clumps of hESCs upon COL4 treatment. 9 Chloroquine, instead of bortezomib, could block COL4-induced protein levels decrease of OCT4 and SOX2. 10 The treatment of COL4 or Rac1 inhibitors could downregulate protein levels of cofilin and SOX2. Conclusion. Upon hESC detachment in cell clumps induced by enzyme treatment, the protein levels of SOX2 and OCT4 decline, which may be related to Rac1/cofilin/F-actin signaling pathway and lysosome. [ABSTRACT FROM AUTHOR]