2020 Vol. 34, No. 5
The recent progress in human genome epidemiology (HuGE) is already having a profound impact on the practice of medicine and public health. First, the success of genome-wide association studies has greatly expanded the direction and content of epidemiological researches, including revealing new genetic mechanisms of complex diseases, identifying new targets for therapeutic interventions, and improving application in early screening of high-risk populations. At the same time, large-scale genomic studies make it possible to efficiently explore the gene-environment interactions, which will help better understand the biological pathways of complex diseases and identify individuals who may be more susceptible to diseases. Additionally, the emergence of systems epidemiology aims to integrate multi-omics together with epidemiological data to create a systems network that can comprehensively characterize the diverse range of factors contributing to disease development. These progress will help to apply HuGE findings into practice to improve the health of individuals and populations.
Obesity and the metabolic syndrome are becoming increasingly prevalent not only in adults, but also in adolescents. The metabolic syndrome, a complex cluster of metabolic abnormalities, increases one's risk of developing type 2 diabetes and cardiovascular disease (CVD). Dyslipidemia, a key component of the metabolic syndrome, is highly associated with insulin resistance and contributes to increased CVD risk. Dyslipidemia has traditionally been assessed using a fasting lipid profile [i.e. fasting triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)]. However, the postprandial state predominates over the course of a day and non-fasting triglycerides independently predict CVD risk. In insulin resistant states, the intestine overproduces triglyceride-rich lipoprotein (TRL) particles, termed chylomicrons (CMs), following ingestion of a fat-containing meal, as well as in the fasting state. Along with elevated hepatic TRLs (i.e. very-low density lipoproteins), CMs contribute to remnant lipoprotein accumulation, small dense LDL particles, and reduced HDL-C, which collectively increase CVD risk. Given the early genesis of atherosclerosis and physiological metabolic changes during adolescence, studying postprandial dyslipidemia in the adolescent population is an important area of study. Postprandial dyslipidemia in the pediatric population poses a significant public health concern, warranting a better understanding of its pathogenesis and association with insulin resistance and CVD. This review discusses the metabolic syndrome, focusing on the link between insulin resistance, postprandial dyslipidemia, and CVD risk. Furthermore, the clinical significance and functional assessment of postprandial dyslipidemia, specifically in the adolescent population, is discussed in more detail.
Morphological and functional abnormalities of vascular endothelial cells (VECs) are risk factors of ischemia-reperfusion in skin flaps. Signaling pathway mediated by interleukin-1 receptor (IL-1R) is essential to hypoxia/reoxygenation (H/R) injury of VECs. While the TIR/BB-loop mimetic (AS-1) disrupts the interaction between IL-1R and myeloid differentiation primary-response protein 88 (MyD88), its role in the VECs dysfunction under H/R is unclear. In this study, we first showed that there was an infiltration of inflammatory cells and the apoptosis of VECs by using a skin flap section from patients who received flap transplantation. We then showed that the H/R treatment induced apoptosis and loss of cell migration of endothelial cell line H926 were attenuated by AS-1. Furthermore, our data suggested that AS-1 inhibits the interaction between IL-1R and MyD88, and subsequent phosphorylation of IκB and p38 pathway, as well as the nuclear localization of NF-KB subunit p65/p50. Thus, this study indicated that the protective role of AS-1 in H/R induced cellular injury may be due to the AS-1 mediated down-regulation of IL-1R signaling pathway.
Renal epithelial sodium channel (ENaC) plays a crucial role in maintaining homeostasis and sodium absorption. While insulin participates in controlling sodium transport across the renal epithelium, the underlying molecular mechanism remain unclear. In this study, we found that insulin increased the expression and function of alpha-epithelial sodium channel (α-ENaC) as well as phosphorylation of cofilin, a family of actin-binding proteins which disassembles actin filaments, in mouse cortical collecting duct (mpkCCDc14) cells. The wild-type (WT) cofilin and its constitutively phosphorylated form (S3D), but not its constitutively non-phosphorylable form (S3A), contributed to the elevated expression on α-ENaC. Overexpression of 14-3-3ε, β, or γ increased the expression of α-ENaC and cofilin phosphorylation, which was blunted by knockdown of 14-3-3ε, β, or γ. Moreover, it was found that insulin increased the interaction between cofilin and 14-3-3 isoforms, which indicated relevance of 14-3-3 isoforms with cofilin. Furthermore, LIMK1/SSH1 pathway was involved in regulation of cofilin and α-ENaC expression by insulin. The results from this work indicate that cofilin participates in the regulation of α-ENaC by interaction with 14-3-3 isoforms.
There were few studies of cumulative live birth rates (CLBRs) based on multicenter reproductive clinical data from the general Chinese population. Here we report a retrospective cohort study, including 14 311 women with 17 315 cycles, in three reproductive centers to evaluate two estimated parameters of CLBRs with multiple transfer cycles of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a Chinese population. We found that CLBRs were related to female age and endometrial thickness. By the fourth transfer cycle, the conservative and optimal estimates of CLBRs were 52.95% and 77.30% in women under 30 years of age, and 18.17% and 26.51% in those 37 years of age or older, respectively. The two estimates were 44.70% and 63.15% in women with endometrial thickness more than 7 mm, and 32.05% and 46.18% in those with less than 7 mm, respectively. In addition, body mass index (BMI), duration of infertility, and infertility diagnoses may also be related to CLBRs on certain conditions. The findings from this study on CLBRs after multiple transfer cycles of IVF/ICSI treatment on different conditions in the Chinese population should be beneficial to both infertile couples and clinicians.
Environmental pollutants, such as bisphenol A (BPA) have recently been implicated in the development of adverse birth outcomes. However, the underlying teratogenic mechanisms remain unclear. We investigated the effects of BPA on the migration and invasion of human primary extravillous trophoblast HTR-8/SVneo cells. Our results indicated that BPA reduced cell migration and invasion. Moreover, it altered the ratio of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) by downregulating MMP-2 and MMP-9, and upregulating TIMP-1 and TIMP-2. Furthermore, BPA suppressed integrin β1, integrin α5, and vimentin. Interestingly, BPA-induced invasion was partially restored by G15, a membrane G-protein-coupled estrogen receptor 30 antagonist. We further revealed that 42 proteins were differentially expressed by mass spectrometry analysis, which could be divided into three categories based on gene ontology including biological process, cellular component, and molecular function. These results suggest that BPA reduces HTR-8/SVneo cell migration and invasion by downregulating MMP-2 and MMP-9, up-regulating TIMP-1 and TIMP-2, and suppressing adhesion molecules.
Thoracolumbar fractures are usually treated by open posterior pedicle screw fixation. However, this procedure involves massive paraspinal muscle stripping, inflicting surgical trauma, and prolonged X-ray exposure. In this study, we observed 127 patients with single-segment injury thoracolumbar fractures. Thirty-six patients were treated by the modified Wiltse's paraspinal approach with minimally invasive channel system, while 91 patients were treated via traditional posterior approach. Operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, screw placement accuracy, visual analogue scale score, and Cobb's angle of two groups were compared. The X-ray exposure times were notably reduced (4.2±1.6) in the new approach group (P<0.05). The pedicle screw placement accuracy and Cobb's angle after surgery were similar in the two groups. We conclude that modified Wiltse's paraspinal approach with spinal minimally invasive channel system surgery can significantly reduce the X-ray exposure times and is an alternative therapy for the thoracolumbar fracture.
With the increasing immunological studies on camels due to the advantage of their single-chain antibodies for humanizations, it is demanding to develop an easy-to-handle evaluation method of their humoral immune response before proceeding with immunization of foreign antigens that may be toxic to camels. In this study, we quantitatively determined the expression levels of T-helper 2 (Th2) cytokines in peripheral blood lymphocytes obtained from Bactrian camels by real-time PCR. The recorded kinetic profiles resulting from the immunization of ovalbumin (OVA) indicated that after immunization, Th2 cytokines including interleukin (IL) families such as IL-4, IL-10, and IL-13 in the camels were up-regulated by a factor of 1.78, 3.15, and 1.22, respectively, which was validated by traditional enzyme-linked immunosorbent assay (ELISA) methods. Unlike ELISA which requires specific enzyme-labeled antibodies, this established method based on the minimal amount of blood samples holds an advantage in the preliminary evaluation of camel humoral immune response with desirable precision, which is meaningful for biomedical explorations of camel-derived antibodies.