Many cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases.
DEDEQIPSHPPR, the calcium-binding peptide (CBP) identified in soy yogurt, was proven to be a potential cofactor in osteoporosis prevention in our previous study, but the mechanism was unknown. In this study, the activity of alkaline phosphatase (ALP) and osteocalcin (OCN), the regulation of RUNX2, and the expression of TβRI were investigated to elucidate the underlying mechanism. The results show that CBP upregulated ALP activity and OCN concentration and increased the expression of RUNX2 and the activation of the MAPK signaling pathway. Similarly, the expression of osteogenesis-related genes in osteoblasts also increased upon CBP treatment. Moreover, the CBP-induced enhancement of ALP activity and phosphorylation levels in the p38 pathway was inhibited by treatment with a p38 inhibitor (SB203538) and TβRI inhibitor (SB431542), respectively, suggesting that p38 and TβRI were involved in the osteogenic action. Based on the signaling pathways, the intracellular calcium concentration was significantly elevated by CBP, which was correlated with the increased behavioral functions and the relative fluorescence intensity of the bone mass. These findings suggest that CBP stimulates osteoblast differentiation and bone mineralization through the activation of RUNX2 via mechanisms related to the TβRI-p38-MAPK signaling pathways, further highlighting CBP’s important potential for treating osteoporosis.
Different from developed countries, there is a paucity of research examining how the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets relate to lipids in in less-developed ethnic minority regions (LEMRs). A total of 83,081 participants from seven ethnic groups were retrieved from the baseline data of the China Multi-Ethnic Cohort (CMEC) study, which was conducted in less-developed Southwest China between May 2018 and September 2019. Multivariable linear regression models were then used to examine the associations of the DASH and AMED scores, assessed by modified DASH score and alternative Mediterranean diet (AMED), as well as their components with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and TC/HDL-C. The DASH scores were negatively associated with TC, HDL-C and TG. Comparing the highest quintiles with the lowest DASH scores, TC decreased 0.0708 (95% CI: −0.0923 ∼ −0.0493) mmol/L, HDL-C decreased 0.0380 (95% CI: −0.0462 ∼ −0.0299) mmol/L, and TG decreased 0.0668 (95% CI: −0.0994 ∼ −0.0341) mmol/L. The AMED scores were negatively associated with TC, LDL-C and HDL-C. Comparing the highest quintiles with the lowest AMED scores, TC decreased 0.0816 (95% CI: −0.1035 ∼ −0.0597) mmol/L, LDL-C decreased 0.0297 (95% CI: −0.0477 ∼ −0.0118) mmol/L, and HDL-C decreased 0.0275 (95% CI: −0.0358 ∼ −0.0192) mmol/L. Although both the DASH diet and the Mediterranean diet were negatively associated with blood lipids, those associations showed different patterns in LEMRs, particularly for TG and HDL-C.
Hyperuricemia is associated with substantial health and economic burden all over the world. Dietary habits are an important influencing factor of hyperuricemia. This study aimed to investigate the relationship between spicy food intake and hyperuricemia based on a large population. A total of 22,125 individuals aged 30–79 were enrolled in China Multi-Ethnic Cohort (CMEC), Chongqing region. Spicy food intake information was collected by a standardized questionnaire. The association between spicy food intake and hyperuricemia was estimated by multivariable logistic regression models and multiple linear regression models. Additionally, we explored these relations in subgroups stratified by sex and age. Furthermore, sensitivity analyses were conducted to verify the stability of current findings. After controlling for potential confounders, compared with participants who never consumed spicy food and consumed less hot, participants who ate 3–5 days per week and very hot had the highest risk of hyperuricemia; the ORs (95% CIs) were 1.28 (1.09, 1.5) and 1.22 (0.92, 1.63), respectively. Additionally, the corresponding ORs (95% CIs) for each level increment in the frequency and degree of pungency in spicy food intake were 1.04 (1.01, 1.07) (P trend = 0.009) and 1.15 (1.04, 1.26) (P trend = 0.004). Further in sex-stratified and age-stratified analysis, similar positive associations were observed among men and those aged 30–59, but no significant association was found among women and those aged 60–79. In the linear regression models, 3–5 days per week and moderate pungency in spicy food intake were associated with 5.21 μmol/L (95% CI: 1.72, 8.70) and 4.69 μmol/L (95% CI: 1.93, 7.45) higher serum urate level. Results in further subgroup analysis were generally consistent with the logistic regression models. This study suggests that spicy food intake may be a risk factor for hyperuricemia, especially in men and younger people, and more studies are warranted to verify the causal associations.
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