KIFC3 promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells by activating EMT and ß-catenin signaling.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. A total of 45 kinesin superfamily proteins (KIFs) have been identified in humans, among which several family members have demonstrated varied functions in tumor pathobiology via different mechanisms, including regulation of cell cycle progression and metastasis. KIFC3 has microtubule motor activity and is involved in cancer cell invasion and migration, as well as survival. However, the role of KIFC3 in ESCC is still unknown. AIM: To evaluate the role of KIFC3 in ESCC and the underlying mechanisms. METHODS: Expression of KIFC3 was evaluated in ESCC tissues and adjacent normal esophageal tissues. The prognostic value of KIFC3 was analyzed using Kaplan-Meier Plotter. Colony formation, EdU assays, cell cycle analysis, Transwell assay, immunofluorescence, and western blotting were performed in ESCC cell lines after transfection with pLVX-Puro-KIFC3-shRNA- and pLVX-Puro-KIFC3-expressing lentiviruses. A xenograft tumor model in nude mice was used to evaluate the role of KIFC3 in tumorigenesis. Inhibitor of ß-catenin, XAV-939, was used to clarify the mechanism of KIFC3 in ESCC. To analyze the differences between groups, t test and nonparametric tests were used. P < 0.05 was considered statistically significant. RESULTS: Immunohistochemical staining indicated that KIFC3 was upregulated in ESCC tissues compared with adjacent normal tissues. Kaplan-Meier Plotter revealed that overexpressed KIFC3 was associated with poor prognosis in ESCC patients. Colony formation and EdU assay showed that KIFC3 overexpression promoted cell proliferation, while KIFC3 knockdown inhibited cell proliferation in ESCC cell lines. In addition, cell cycle analysis showed that KIFC3 overexpression promoted cell cycle progression. KIFC3 knockdown suppressed ESCC tumorigenesis in vivo. Transwell assay and western blotting revealed that KIFC3 overexpression promoted cell migration and invasion, as well as epithelial-mesenchymal transition (EMT), while KIFC3 knockdown showed the opposite results. Mechanistically, KIFC3 overexpression promoted ß-catenin signaling in KYSE450 cells; however, the role of KIFC3 was abolished by XAV-939, the inhibitor of ß-catenin signaling. CONCLUSION: KIFC3 was overexpressed in ESCC and was associated with poor prognosis. Furthermore, KIFC3 promoted proliferation, migration and invasion of ESCC via ß-catenin signaling and EMT.

Pharmacokinetic interaction between a Chinese herbal formula Huosu Yangwei oral liquid and apatinib in vitro and in vivo.

OBJECTIVES: This study aimed to evaluate the inhibitory effects of Huosu Yangwei oral liquid (HSYW) on cytochrome P450 enzymes (CYPs) and to investigate whether this herbal medicine could modulate the pharmacokinetic behaviour of the co-administered CYP-substrate drug apatinib. METHODS: Cytochrome P450 enzymes inhibition assays were conducted in human liver microsomes (HLM) by a LC-MS/MS method for simultaneous determination of the oxidative metabolites of eight probe substrates for hepatic CYPs. The modulatory effects of HSYW on the oxidative metabolism of apatinib were investigated in both HLM and rat liver microsomes (RLM). The influences of HSYW on the pharmacokinetic behaviour of apatinib were investigated in rats. KEY FINDINGS: Huosu Yangwei oral liquid inhibited all tested CYPs in human liver preparations, with the IC50 values ranged from 0.3148 to 2.642 mg/ml. HSYW could also inhibit the formation of two major oxidative metabolites of apatinib in liver microsomes from both human and rat. In-vivo assays demonstrated that HSYW could significantly prolong the plasma half-life of apatinib by 7.4-fold and increase the AUC0-inf (nm·h) of apatinib by 43%, when HSYW (10 ml/kg) was co-administered with apatinib (10 mg/kg) in rats. CONCLUSIONS: Huosu Yangwei oral liquid could inhibit mammalian CYPs and modulated the metabolic half-life of apatinib both in vitro and in vivo.

[Characteristics of Heavy Metal Pollutants of PM2.5 from Open Burning of Municipal Solid Waste (MSW) and the Associated Exposure Health Risks].

The characteristics and health risk assessment for heavy metal pollutants in PM2.5 discharged from the open burning of municipal solid waste (MSW) in different functional areas were studied using a flue gas diluted sampling system. The two common open burning modes of barrel and natural pile-up burning were considered. The results show that the concentration of zinc (Zn) was the highest among the heavy metals produced by five different components of waste incineration, ranging from 1324.03 to 3703.12 mg·kg-1. The concentration of cadmium (Cd) was the lowest, ranging from 20.25 to 63.68 mg·kg-1. According to the geo-accumulation index, lead (Pb), Zn, arsenic (As), and Cd were highly polluted in the measured MSW samples, and all four of these metals reached moderate or higher levels of pollution under natural pile-up burning methods. The geo-accumulation index of Cd was much higher than 5. The results of the human health risk assessment showed that non-carcinogenic risk values for 8 heavy metals (Pb, Zn, Cu, Mn, As, Cd, Cr, and Ni) by respiratory exposure were less than 1, which is within the safe range. For natural pile-up burning, the total non-carcinogenic risk values for As and Pb for children were higher than 1, indicating a non-carcinogenic risk. The carcinogenic risk values for four carcinogenic elements (As, Cd, Cr, and Ni) were less than 1.0×10-4, but still represented a low potential carcinogenic risk under exposure for long periods of time.

[Angiotensin II type 1 receptor autoantibody induces myocardial fibrosis by activating cardiac fibroblasts].

Myocardial fibrosis (MF) is an important pathological process of cardiac remodeling in patients with heart failure; however its etiology has not been clear. It has been known that the angiotensin II type 1 receptor autoantibody (AT1-AA) is present in patients with heart failure, but it is unclear whether this antibody directly causes MF. In this study, we investigated the role of AT1-AA in MF and its effects on cardiac fibroblasts (CFs). The AT1-AA positive rat model was established by active immunization method, and the measurement of indexes were made in the 8th week after active immunity. The results of heart echocardiography showed that the cardiac systolic and diastolic functions of AT1-AA positive rats were impaired with reduced left ventricular wall thickness and enlarged heart chambers. HE staining results showed that the myocardial fibers were disorganized and ruptured, and Masson staining revealed that the area of collagen fibers around the myocardium and coronary arteries was significantly increased in AT1-AA positive group compared with that of the control group (P < 0.05). Moreover, primary CFs isolated from neonatal rats were cultured and treated with AT1-AA for 48 h. CCK-8 and immunofluorescence staining results showed that AT1-AA enhanced proliferation rate of CFs (P < 0.001), and Western blot results showed that AT1-AA significantly increased expressions of collagen I (Col I), Col III, matrix metalloproteinase-2 (MMP-2) and MMP-9 in CFs (all P < 0.05). Taken together, these results suggest that AT1-AA may induce MF and cardiac dysfunction via activating CFs.

[Emission Characteristics and Chemical Components of PM2.5 from Open Burning of Municipal Solid Waste].

Source emission measurements were employed to investigate open burning of municipal solid waste (MSW). Both barrel and natural pile-up burning of MSW were investigated using a self-designed dilution sampling system. PM2.5 was collected for three types of waste, including rubber and plastic, paper, and wood and bamboo. Then, components in the samples were analyzed and emission factors of PM2.5, organic carbon (OC), elemental carbon (EC), water-soluble ions and inorganic elements were calculated. The PM2.5 emission factor was highest for wood and bamboo, and lowest for paper, and was calculated to be (7.44±0.76) g·kg-1 and (2.72±0.52) g·kg-1, respectively. Barrel burning resulted in much higher pollutant emissions. The PM2.5 emission factor for barrel burning was 2.5-3.5 times that of natural pile-up burning. OC and EC were the main components of PM2.5, with a proportion of 46.6%-67.2%. MSW composition had a greater effect on the OC/EC ratios than burning mode. The ratios could be helpful in the analysis of the emission contributions of different MSW components. The proportions of NH4+ and Cl- were the highest in water-soluble ions, accounting for 2.28%-6.35% and 1.04%-14.31%, respectively. Among inorganic elements, Ca, K, Fe, and Ba showed high emission factors. The emission factor of Zn was the highest among heavy metals, and other elements such as Cu, Cr, Sb, and Pb were also enriched. Zn emission was mainly determined by the burning mode; emissions from barrel combustion were approximately 20 times more than that of natural pile-up burning.

[Determination of dissolution of liuwei dihuang concentrated pills based on multi-index components].

With the content of gallic acid, loganin, paeoniflorin and paeonol as the indexes, to screen out dissolution determination conditions, establish the dissolution determination method for multi-index components in Liuwei Dihuang concentrated pills, calculate and map the accumulative dissolution curve, and then compare the dissolution of products from different pharmaceutical factories through the similarity factor (f2). According to the results, the optimum dissolution determination conditions were the paddle method, with 250 mL 0.1 mol x L(-1) hydrochloric acid as the dissolution medium, and a rotation rate of 100 r x min(-1). The similarity factor values (f2) of the dissolution curves of the four main components of Liuwei Dihuang concentrated pills from different pharmaceutical factories were mostly less than 50. This demonstrated a significant difference in the dissolution of Liuwei Dihuang concentrated pills from different pharmaceutical factories, and provided scientific basis for improving the equality evaluation of Liuwei Dihuang concentrated pills.

Production and characterization of interspecific somatic hybrids between Brassica oleracea var. botrytis and B. nigra and their progenies for the selection of advanced pre-breeding materials.

Somatic hybridization is a potential method for gene transfer from wild relatives to cultivated crops that can overcome sexual incompatibilities of two distantly related species. In this study, interspecific asymmetric somatic hybrids of Brassica oleracea var. botrytis (cauliflower) and Brassica nigra (black mustard) were obtained by protoplast fusion and their backcrossed (BC(3)) and selfed (S(3)) offspring were analyzed. Cytological analysis showed that the B. nigra chromosomes were successively eliminated in the backcrosses with cauliflower. The fertility of the hybrid progenies was quite different due to the asynchronous and abnormal chromosome behavior of pollen mother cells (PMC) during meiosis. Analysis of sequence-related amplified polymorphism (SRAP) showed that all of these hybrids mainly had the DNA banding pattern from the two parents with some alterations. Genetically, the selfed generations were closer to B. nigra, while the backcrossed generations were closer to the cauliflower parent. Analysis of cleaved amplified polymorphic sequences (CAPS) and restriction fragment length polymorphisms (RFLP) showed that all somatic hybrids in this study contained chloroplast (cp) DNA of the donor parent black mustard, while mitochondrial (mt) DNA showed evidence of recombination and variations in the regions analyzed. Furthermore, three BC(3) plants (originated from somatic hybrids 3, 4, 10) with 2-8 B. nigra-derived chromosomes shown by genomic in situ hybridization (GISH) displayed a more cauliflower-like morphology and high resistance to black-rot. These plants were obtained as bridge materials for further analysis and breeding.

[Effects of acute moderate hypoxia on plasma angiotensin II and adrenomedullin in pilots].

Objective. To study the effect of acute moderate hypoxia on plasma angiotensin II (AII) and adrenomedullin (ADM) content in pilots. Method. The concentration of plasma AII and ADM was measured by radioimmunoassay in 16 healthy male pilots in the early morning (6:00), following acute moderate hypoxic exposure (10:00) and 6 h after returned to the ground (16:00). Sixteen healthy male ground crews were set as control group, and their plasma AII and ADM content was assayed at corresponding time. Result. 1) Plasma AII and ADM content of pilot group and that of the control group was not different (P>0.05). 2) Plasma AII and ADM content immediately after acute moderate hypoxic exposure in the pilot group was significantly higher than that of before hypoxia (P<0.05), and it returned to normal level 6 h after hypoxia. Conclusion. Acute moderate hypoxia can induce temporarily increase of plasma AII and ADM in pilots.