PLAU, transcriptionally negatively regulated by GATA6, promotes lung squamous carcinoma cell proliferation and migration.

BACKGROUND: Lung squamous cell carcinoma (LUSC) is associated with high mortality and has limited therapeutic treatment options. Plasminogen activator urokinase (PLAU) plays important roles in tumor cell malignancy. However, the oncogenic role of PLAU in the progression of LUSC remains unknown. GATA-binding factor 6 (GATA6), a key regulator of lung development, inhibits LUSC cell proliferation and migration, but the underlying regulatory mechanism remains to be further explored. Moreover, the regulatory effect of GATA6 on PLAU expression has not been reported. The aim of this study was to identify the role of PLAU and the transcriptional inhibition mechanism of GATA6 on PLAU expression in LUSC. METHODS: To identify the potential target genes regulated by GATA6, differentially expressed genes (DEGs) obtained from GEO datasets analysis and RNA-seq experiment were subjected to Venn analysis and correlation heatmap analysis. The transcriptional regulatory effects of GATA6 on PLAU expression were detected by real-time PCR, immunoblotting, and dual-luciferase reporter assays. The oncogenic effects of PLAU on LUSC cell proliferation and migration were evaluated by EdU incorporation, Matrigel 3D culture and Transwell assays. PLAU expression was detected in tissue microarray of LUSC via immunohistochemistry (IHC) assay. To determine prognostic factors for prognosis of LUSC patients, the clinicopathological characteristics and PLAU expression were subjected to univariate Cox regression analysis. RESULTS: PLAU overexpression promoted LUSC cell proliferation and migration. PLAU is overexpressed in LUSC tissues compared with normal tissues. Consistently, high PLAU expression, which acts as an independent risk factor, is associated with poor prognosis of LUSC patients. Furthermore, the expression of PLAU is transcriptionally regulated by GATA6. CONCLUSION: In this work, it was revealed that PLAU is a novel oncogene for LUSC and a new molecular regulatory mechanism of GATA6 in LUSC was unveiled. Targeting the GATA6/PLAU pathway might help in the development of novel therapeutic treatment strategies for LUSC.

Genetic polymorphisms of superoxide dismutase 1 are associated with the serum lipid profiles of Han Chinese adults in a sexually dimorphic manner.

Inspired by the mechanistic correlations between superoxide dismutase 1 (SOD1) and lipid metabolism, the associations of SOD1 single nucleotide polymorphisms (SNPs) with circulating lipid levels were explored. In 2621 Chinese Han adults, randomly recruited from a health examination center without organic diseases, cancers, and pregnancy, three tag SNPs, rs4998557, rs1041740, and rs17880487 selected by Haploview software were genotyped with a probe-based real-time quantitative PCR method. In both genders, most parameters of the dyslipidemia adults were inferior (P < 0.001) to those of the non-dyslipidemia adults, and genotype frequencies of rs4998557 and rs17880487 were significantly different (P < 0.05) between the normal and abnormal subgroups of total cholesterol (TC) or high-density lipoprotein cholesterol (HDLC). Adjusted for confounding factors, logistic regression analyses revealed that in males rs4998557A, rs1041740T, and rs17880487T reduced the risk of high TC and/or LDLC (P < 0.05), and rs4998557A and rs17880487T increased the risk of low HDLC (P < 0.05); but in females, none of the SNPs had associations with any of the lipid parameters (P > 0.05). Conclusively, characterized by a sexual dimorphism, the SOD1 polymorphisms were associated with the lipid disorders in the adult males but not females of the Chinese Han population.

High serum concentration of selenium, but not calcium, cobalt, copper, iron, and magnesium, increased the risk of both hyperglycemia and dyslipidemia in adults: A health examination center based cross-sectional study.

BACKGROUND: Metabolic disorders of glucose and lipid were associated with some mineral elements, and data were warranted from various contexts to make the association more explicit. OBJECTIVE: To investigate the relationships between the serum concentrations of six mineral elements (calcium, cobalt, copper, iron, magnesium, and selenium) and the risk of hyperglycemia and dyslipidemia in adults. METHODS: The basic information and the over-night fasting serum samples of adults were randomly collected at a health examination center. The serum concentrations of glucose and lipids were measured with an automatic biochemical analyzer, and the mineral elements were measured with an inductively coupled plasma mass spectrometer. Data were analyzed between the hyperglycemia group (HGg) and the normal glucose group (NGg) as well as between the dyslipidemia group (DLg) and the normal lipid group (NLg). RESULTS: A total of 1466 adults aged 22-81 years (male/female = 1.8) were included, 110 in the HGg and 1356 in the NGg, or 873 in the DLg and 593 in the NLg. The serum element concentration medians [P50 (P25-P75)] significantly different between the HGg and the NGg were 0.83 (0.75-0.94) vs. 0.76 (0.68-0.87) mg/L for copper and 100 (90-110) vs. 94 (87-103) µg/L for selenium (P < 0.001), while those between the DLg and the NLg were 99 (92-110) vs. 97 (90-106) mg/L for calcium, 0.78 (0.69-0.88) vs. 0.75 (0.66-0.85) mg/L for copper, 1.7 (1.4-2.0) vs. 1.6 (1.3-2.0) mg/L for iron, 24 (22-28) vs. 23 (22-27) mg/L for magnesium, and 97 (89-106) vs. 92 (84-100) µg/L for selenium (P < 0.05). When the copper and selenium between the HGg and the NGg were analyzed by logistic regression with age, gender, body mass index, and mineral elements adjusted, only the highest quartile of selenium concentration had association with the increased risk of hyperglycemia [quartile (Q) 4 against Q1: OR = 2.9, 95 % CI = 1.5-5.5, P < 0.001). When the five differed mineral elements between the DLg and the NLg were similarly analyzed, only iron and selenium had associations with the increased risk of dyslipidemia (e.g., Q4 against Q1: OR = 1.4, 95 % CI = 1.1-2.0 for iron and OR = 2.9, 95 % CI = 2.1-4.0 for selenium, P < 0.05). CONCLUSION: In contrast to those of calcium, cobalt, copper, iron, and magnesium, the higher serum concentration of selenium increased the risk of both hyperglycemia and dyslipidemia in the study population of adult Chinese.

The GC2 haplotype of the vitamin D binding protein is a risk factor for a low plasma 25-hydroxyvitamin D concentration in a Han Chinese population.

BACKGROUND: The GC haplotype of the vitamin D binding protein (encoded by the GC gene) might be a risk factor to the vitamin D (VD) nutritional status for many populations, while evidences from the Chinese Han population are sparse. We test the association between vitamin D binding protein genotypes and VD status as well as the metabolic parameters of glucose and lipids in a Han Chinese population. METHODS: In a cross-sectional study conducted at a health examination centre (registered in ClinicalTrials.gov as QLS2013), 2641 adults were included and grouped according to their plasma 25-hydroxyvitamin D (25OHD) concentrations as VD deficient (VDD), insufficient (VDI), or sufficient (VDS). The rs7041 and rs4588 genotypes were analysed with a molecular beacon-based qPCR method using blood samples. RESULTS: Plasma 25OHD concentrations were lower in the GC2/2, rs7041T/T, and rs4588A/A genotypes than the GC1f/1s, rs7041G/T, and rs4588C/C genotypes (P <  0.05). After adjusting for confounders, the GC2 haplotype increased the risk of low VD status (P <  0.05) in both genders. More genotypic models revealed the negative contributions of rs4588A than rs7041T to low VD status (P <  0.05). The combined rates of VDD and VDI were 80.2% in males and 86.1% in females. Compared with VDI, VDS, or both, VDD showed higher plasma concentrations of fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides in males (P <  0.05); however, no significant differences were found with regard to these parameters between the subgroups defined by the GC genotypes (P > 0.05). CONCLUSIONS: In a Han Chinese population, the GC2 haplotype or more exactly rs4588A is a risk factor for low VD status but is not associated with glucose and lipid metabolic disorders, which are inversely correlated with the circulating 25OHD concentration in males. TRIAL REGISTRATION: The study was retrospectively registered in January 2018 as NCT03406234 in the ClinicalTrials.gov online system.

[Body composition investigation of 2321 Shenzhen government and enterprise staffs].

OBJECTIVE: To understand the laws of human body composition change and the status of the overweight and obesity of government and enterprise staffs. METHODS: In July 2013 - January 2014, 2321 adults more than 20-year-old healthy check-up crowd with complete human body composition and height as well as weight data in a medical center in Shenzhen were collected by convenience sampling method. RESULTS: The overweight rates of male and female were 46.41% and 18.94% respectively (standardized overweight rates were 44.02% and 14.51%, respectively), and the difference between them was statisically significant (Χ2 = 201.01, P = 0. 000). The obesity rates of male and female were 12.13% and 3.57%, respectively (standardized overweight rates were 11.11% (see symbol) 2.63%, respectively), and the difference between them was statisically significant (X2 = 48.45, P = 0.000). The parameters of bone mineral quality, visceral fat area, body fat, body fat percentage, abdominal obesity, body moisture and free fat weight increased with body weight, and there were statistical significance among normal weight, overweight and obesity groups (P = 0.000). Bone mineral quality was highest at the age of 30 to 40 for men and women, and there was the statistical significance. There was statistical significance in visceral fat area between different ages in the same gender. Body fat percentage (34.24 + 5.39)% of all ages 50 to 59 years old and body moisture (28.53 + 3.77)% of age 40 - 49 group were highest in women. Male body fat percentage (27.08 + 5.01)% at the age of 60-age group was the highest. Male and female visceral fat area increasesd with age, but there was no statistical difference between men and women at the same age. The human body composition had not a statistically significant difference among normal weight and overweight groups, but a significant difference between normal weight and obesity groups (P = 0.000). CONCLUSION: Overweight and obesity rates in Shenzhen government and enterprise staffs increase with age. Body composition increase with the weight.

Synergic analysis of upper limb target-reaching movements.

The topological invariance and synergies of human movements are discussed through the analysis and comparison of upper-limb target-reaching tasks. Five subjects were asked to perform different target-reaching tasks with different indices of difficulty, and the movements were captured using a Vicon 3D motion analysis system. Topological invariance was observed in the trajectories of different task performances. After normalization, the trajectories of the arm tips had very close patterns for different target-reaching tasks. Synergy in the target-reaching movements of the upper limbs was also found among the different joint angles. The joint angles can be fitted using the same format of functions proposed in this study. The parameters in the function can be taken as a characteristic feature of target-reaching movement patterns. A target-reaching movement can be determined by these parameters and the start and end positions.

Motion quality evaluation of upper limb target-reaching movements.

Fitts' Law was extended in the polar coordinate system, and a set of indices for human motion evaluation is proposed. In this paper, the index of difficulty and the index of performance are introduced as the general indices for the quality measure of plane target-to-target movement. As an example, the target-reaching movement of the upper limb, which is a basic functional action of upper limbs in the activities of daily living, was experimentally investigated. Five healthy subjects were asked to perform six target-reaching tasks with different indices of difficulty. All movements were recorded using a Vicon motion analysis system. The movement quality was measured using these evaluation indices.