Two New 3D Supramolecular Complexes: Photocatalytic Properties and Treatment Activity for Gastric Cancer.

Two new coordination polymers, [Cu2(5-MeO-Hip)4(py)4]n (1) and [Co(5-EtO-ip)(4,4'-bipy)]n·n(MeOH) (2) (5-MeO-H2ip is 5-methoxyisophthalic acid, 5-EtO-H2ip is 5-ethoxyisophthalic acid, py is pyridine, and 4,4'-bipy is 4,4'-bipyridine), were created via solvothermal self-assembly. The thermal steadiness and photocatalytic functions of 1 and 2 were detected, and their application values in gastric cancer and the related mechanism were discussed. CCK-8 assay was used to determine the inhibitory activity toward gastric cancer cells' viability, and real-time RT-PCR was employed to examine the gastric cancer cells' Notch signaling pathway activity.

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/ß-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression.

Circular RNAs (circRNAs) have been reported to be involved in the progression of papillary thyroid carcinoma (PTC). However, the role of circular RNA Pvt1 oncogene (circPVT1) in PTC has rarely been reported. In this study, we aimed to investigate the function and mechanism of circPVT1 in PTC. The expression level of circPVT1, miR-195 and VEGFA were determined by reverse transcription­quantitative PCR (RT­qPCR). Fisher's exact test was used to analyze the correlation between circPVT1 expression and PTC clinical features. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) staining assay and transwell assay were conducted to evaluate the cell proliferation, migration and invasion ability. Dual-luciferase reporter and Western blot assay were conducted for evaluating the correlation between miR-195 and circPVT1 or VEGFA. The results of RT-PCR showed that the expression level of circPVT1 was significantly upregulated in PTC tissues and cell lines. After downregulating circPVT1 expression in PTC cells, the abilities of cell proliferation, migration, and invasion were obviously suppressed, and the Wnt/ß-catenin signaling pathway was also repressed. Besides, miR-195 could both bind to PVT1 and VEGFA, while PVT1 could promote the expression of VEGFA by binding to miR-195. Downregulation of VEGFA expression in PTC cells revealed weakened cell proliferation, migration, and invasion capacities, and restrained Wnt/ß-catenin signaling pathway. Therefore, we demonstrated that circPVT1 could promote VEGFA expression by sponging miR-195. CircPVT1 could serve as a molecule sponge for miR-195 and mediate the ceRNA network to promote the expression of VEGFA, thus contributed to the malignant progression of PTC.

CircRNA_104565 Promoted Cell Proliferation in Papillary Thyroid Carcinoma by Sponging miR-134.

BACKGROUND: Thyroid cancer is one of the most common cancers with rising incidence worldwide, and papillary thyroid carcinoma (PTC) accounts for 80-85% of thyroid malignancy. Although it has been reported that many genes relate to the carcinogenesis of PTC, the molecular mechanisms remain mostly unclear. METHODS: QRT-PCR assay was performed to detect circRNA_104565, miR-134 and ELF2 expression. CCK8 assay was exercised to examine cell proliferation. Western blot was used to detect ELF2 expression. RESULTS: We found that circRNA_104565 was highly expressed in PTC tissue and cell and promoted cell proliferation in vitro and in vivo. In addition, circRNA_104565 promoted cell proliferation in PTC by regulating the miR-134/ELF2 axis. CONCLUSION: Hence, revealing the function of circRNA_104565 in PTC is important for understanding the molecular mechanism of carcinogenesis and providing new biomarkers or therapeutic targets for PTC.

Effect of bevacizumab combined with docetaxel in the treatment of HER-2-negative recurrent metastatic breast cancer.

PURPOSE: To explore the efficacy and safety of bevacizumab combined with docetaxel in the treatment of human epidermal growth factor receptor-2 (HER-2)-negative recurrent metastatic breast cancer. METHODS: The clinical data of 128 patients with HER-2-negative recurrent metastatic breast cancer treated in our hospital from January 2015 to December 2016 were retrospectively analyzed. Sixty-four patients were treated with bevacizumab combined with docetaxel (Bevacizumab group), while the remaining 64 patients were treated with docetaxel alone (Docetaxel group). The clinical efficacy and adverse reactions were compared between the two groups, and the expressions of Ki-67, p53, matrix metalloproteinase-2 (MMP-2) and MMP-9 in breast cancer tissues were compared in both groups before and after treatment. The patient survival status and progression of disease were recorded through follow-up. RESULTS: In Bevacizumab group and Docetaxel group, the objective response rate (ORR) was 57.8% and 39.1%, and the clinical benefit rate (CBR) was 90.6% and 81.3%, respectively. The ORR was significantly better in Bevacizumab group than that in Docetaxel group. There was no statistically significant difference in the incidence rate of adverse reactions between the two groups. After treatment, the positive expression rates of Ki-67, p53, MMP-2 and MMP-9 obviously declined in both groups compared with those before treatment, showing statistically significant differences between the two groups. In Bevacizumab group and Docetaxel group, the mean overall survival (OS) was 13.3±5.5 months and 11.7±5.0 months, and the mean progression-free survival (PFS) was 7.1±2.6 months and 6.6±2.3 months, respectively. According to log-rank test, the OS rate was remarkably superior in Bevacizumab group to that in Docetaxel group (p=0.041), while the PFS rate had no statistically significant difference between the two groups (p=0.095). CONCLUSIONS: Bevacizumab combined with docetaxel has more excellent efficacy than docetaxel alone in the treatment of HER-2-negative recurrent metastatic breast cancer, and it prolongs the survival of patients, with tolerable adverse reactions, which is worthy of further clinical application.

Circular RNA-9119 suppresses in ovarian cancer cell viability via targeting the microRNA-21-5p-PTEN-Akt pathway.

We aimed to assess the regulatory role of circular RNA (circRNA)-9119 (circ9119) in ovarian cancer (OC) cell viability. The expression of circ9119 was clearly reduced in OC tissues and cell lines, whereas the microRNA-21-5p (miR-21) levels were elevated compared with those in normal healthy control tissues and immortalized fallopian epithelial cell line FTE187. Further, circ9119 was overexpressed, causing a notable decrease in the viability and proliferation of OC cells and an increase in apoptosis. Further study showed that circ9119 upregulation resulted in a decrease in miR-21 levels. Bioinformatics forecasting (starBase and TargetScan) and dual luciferase reporter assay demonstrated that circ9119 acts as an miR-21 sponge. Recovery of miR-21 expression in circ9119-overexpressing OC cells showed that miR-21 exhibited the opposite effect on circ9119; moreover, its recovery could suppress the effects of circ9119 overexpression, recover cell proliferation, and reduce apoptosis. Furthermore, miR-21 was found to target phosphatase and tensin homologue (PTEN) 3' untranslated region. PTEN protein and mRNA expression was reduced in OC tissues and cells, whereas it was increased on transfection with an miR-21 inhibitor. Thus, circ9119 could regulate cell proliferation and apoptosis of OC cells via by acting as an miR-21 sponge and targeting the PTEN-Akt pathway.

LncRNA MIR4435-2HG is a potential early diagnostic marker for ovarian carcinoma.

LncRNA MIR4435-2HG is characterized as an oncogene in lung cancer. However, its role in ovarian carcinoma (OC) is unclear. In this study, we aimed to investigate the role of MIR4435-2HG in OC. We found that both MIR4435-2HG and transforming growth factor beta 1 (TGF-ß1) were upregulated in OC. MIR4435-2HG is associated with tumor metastasis but not with tumor size. Upregulation of MIR4435-2HG distinguished early stage (Stage I and II) OC patients from healthy controls. Correlation analysis showed that plasma levels of MIR4435-2HG and TGF-ß1 were positively correlated only in OC patients. qPCR and western blot analysis results showed that MIR4435-2HG overexpression led to upregulation of TGF-ß1 in OC cells, while TGF-ß1 treatment did not significantly affect MIR4435-2HG expression. Transwell invasion and migration assays showed that MIR4435-2HG and TGF-ß1 promoted the invasion and migration of OC cells while TGF-ß inhibitor suppressed the invasion and migration of these cells. Further analysis of the Transwell invasion and migration assay results showed that TGF-ß inhibitor reduced the effects of MIR4435-2HG overexpression. Therefore, our results suggested that lncRNA MIR4435-2HG may promote OC by upregulating TGF-ß1. Further characterization of the functions of MIR4435-2HG in OC may provide novel targets for cancer therapies.

Warm Pre-Strain: Strengthening the Metastable 304L Austenitic Stainless Steel without Compromising Its Hydrogen Embrittlement Resistance.

Plastic pre-strains were applied to the metastable 304L austenitic stainless steel at both room temperature (20 °C) and higher temperatures (i.e., 50, 80 and 100 °C), and then the hydrogen embrittlement (HE) susceptibility of the steel was evaluated by cathodically hydrogen-charging and tensile testing. The 20 °C pre-strain greatly strengthened the steel, but simultaneously significantly increased the HE susceptibility of the steel, since α' martensite was induced by the pre-strain, causing the pre-existence of α' martensite, which provided "highways" for hydrogen to transport deep into the steel during the hydrogen-charging. Although the warm pre-strains did not strengthen the steel as significantly as the 20 °C pre-strain, they retained the HE resistance of the steel. This is because the higher temperatures, particularly 80 and 100 °C, suppressed the α' martensite transformation during the pre-straining. Pre-strain at a temperature slightly higher than room temperature has a potential to strengthen the metastable 304L austenitic stainless steel without compromising its initial HE resistance.

Nicotinic acid supplementation in diet favored intramuscular fat deposition and lipid metabolism in finishing steers.

Nicotinic acid (NA) acting as the precursor of NAD(+)/NADH and NADP(+)/NADPH, participates in many biochemical processes, e.g. lipid metabolism. The main purpose of this study was to investigate the effects of dietary NA on carcass traits, meat quality, blood metabolites, and fat deposition in Chinese crossbred finishing steers. Sixteen steers with the similar body weight and at the age of 24 months were randomly allocated into control group (feeding basal diet) and NA group (feeding basal diet + 1000 mg/kg NA). All experimental cattle were fed a 90% concentrate diet and 10% forage straw in a 120-day feeding experiment. The results showed that supplemental NA in diet increased longissimus area, intramuscular fat content (17.14% vs. 9.03%), marbling score (8.08 vs. 4.30), redness (a*), and chroma (C*) values of LD muscle, but reduced carcass fat content (not including imtramuscular fat), pH24 h and moisture content of LD muscle, along with no effect on backfat thickness. Besides, NA supplementation increased serum HDL-C concentration, but decreased the serum levels of LDL-C, triglyceride, non-esterified fatty acid, total cholesterol, and glycated serum protein. In addition, NA supplementation increased G6PDH and ICDH activities of LD muscle. These results suggested that NA supplementation in diet improves the carcass characteristics and beef quality, and regulates the compositions of serum metabolites. Based on the above results, NA should be used as the feed additive in cattle industry.

Daidzein enhances intramuscular fat deposition and improves meat quality in finishing steers.

An experiment was conducted to determine the effects of soy isoflavone daidzein on carcass characteristics, fat deposition, meat quality, and blood metabolites in finishing steers. Fourteen crossbred steers were used in a 120-d finishing study. These steers were stratified by weight into groups and randomly allotted by group to one of two dietary treatments: (1) control and (2) daidzein (500 mg/kg concentrate). The steers were fed a 90% concentrate diet. Supplemental daidzein did not affect slaughter weight, hot carcass weight, and dressing percentage, but tended to reduce fat proportion (not including intramuscular fat) in carcass and backfat thickness of steers. The carcass bone proportion was greater in steers fed daidzein diets than those fed control diets. Daidzein supplementation reduced pH at 24 h after slaughtered and moisture content and increased isocitrate dehydrogenase activity, fat content (16.28% and 7.94%), marbling score (5.29 and 3.36), redness (a*), and chroma (C*) values in longissimus muscle relative to control treatment. The concentrations of blood metabolites including glucose, blood urea nitrogen, triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were all lower in steers fed daidzein diets than those fed control diets. Current results suggest that supplemental daidzein can affect lipid metabolism, increase intramuscular fat content and marbling score, and improve meat quality in finishing steers. Daidzein should be a promising feed additive for production of high-quality beef meat.

Single nucleotide polymorphisms of toll-like receptor 7 in hepatitis C virus infection patients from a high-risk chinese population.

Hepatitis C virus (HCV) infection varies in the outcomes depending on both viral and host factors. This study aims to investigate the associations of three single nucleotide polymorphisms (SNPs) of Toll-like receptor 7 (TLR7), rs179016, rs5743733, and rs1634323, with susceptibility to HCV infection and clearance. The three SNPs were genotyped in a high-risk Chinese population, including 444 HCV spontaneous clearance cases, 732 persistent infection cases, and 1107 healthy controls. The G allele of rs1634323 was related to the protection from persistent infection among females (dominant model: odds ratio (OR) = 0.558, 95 % confidence interval (CI) = 0.348-0.894, P = 0.015). This protective effect was more evident in blood donation and HCV non-1 genotype-infected subgroups (all P < 0.05). The carriage of rs179016 C allele was more prone to develop persistent infection (OR = 1.444, 95 % CI = 1.096-1.903, P = 0.009) in males, and the risk effect remained significant among older (>50 years), hemodialysis (HD), and HCV-1 and HCV non-1 genotypes-infected subjects (all P < 0.05). Haplotype analyses showed that CCA haplotype among females was correlated with the elevated risk of HCV susceptibility while the carriage of GGA was more prone to be infected with HCV and CCA was more likely to develop persistent infection (all P < 0.05) among males. Our results first demonstrated that the carriage of rs179016 C allele had a negative effect on spontaneous clearance of HCV among males while rs1634323 G allele conferred a protective effect against persistent infection among female subjects.

Effect of lipoxin A4 on lipopolysaccharide-induced endothelial hyperpermeability.

Excessive oxidative stress, decreased antioxidant capacity, and enhanced cellular calcium levels are initial factors that cause endothelial cell (EC) hyperpermeability, which represents a crucial event in the pathogenesis of pre-eclampsia. Lipoxin A4 (LXA4) strongly attenuated lipopolysaccharide (LPS)-induced hyperpermeability through maintaining the normal expression of VE-cadherin and â-catenin. This effect was mainly mediated by a specific LXA4 receptor. LXA4 could also obviously inhibit LPS-induced elevation of the cellular calcium level and up-regulation of the transient receptor potential protein family C 1, an important calcium channel in ECs. At the same time, LXA4 strongly blocked LPS-triggered reactive oxidative species production, while it promoted the expression of the NF-E2 related factor 2 (Nrf2) protein. Our findings demonstrate that LXA4 could prevent the EC hyperpermeability induced by LPS in human umbilical vein endothelial cells (HUVECs), under which the possible mechanism is through Nrf2 as well as Ca2+-sensitive pathways.

[Effect of lipoxin A(4) on lipopolysaccharide-induced endothelial hyperpermeability in human umbilical vein endothelial cell].

OBJECTIVE: To explore whether lipoxin A(4) (LXA(4))could prevent lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVEC) monolayer hyperpermeability and its possible mechanism. METHODS: Human umbilical cords were obtained from women with normal pregnancy immediately after delivery from Tongji Hospital Affiliated of Tongji Medical College. Primary HUVEC were isolated from umbilical veins and subcultured, then, HUVEC were divided into four groups:control group; LPS group (10 mg/L of LPS); LPS + LXA(4) group(10 mg/L of LPS and 100 nmol/L of LXA(4)); LPS + LXA(4) + BOC-2 group [10 µmol/L of BOC-2, an effective antagonist of formyl peptide receptor like 1 (FPRL-1)]. All expriments were performed after cells were treated for 24 hours. Endothelial permeability was measured by fluorescein isothiocyan-ate labelled bovine serum albumin (FITC-BSA) clearance across the monolayer; tumor necrosis factor α (TNF-α) mRNA and secretion were detected by reverse transcriplase (RT)-PCR and ELISA assay respectively, and nuclear factor κB (NF-κB) protein change was determined by western blot. RESULTS: (1) LPS induced a significant increase in the permeability [Pa value of LPS group was (183.1 ± 1.7)%], while co-administrating with LXA(4) obviously attenuated this LPS-induced hyperpermeability, Pa value of LPS + LXA(4) group was (103.1 ± 2.2)%, LPS + LXA(4) + BOC-2 group was (162.2 ± 2.8)%, control group was 100%, the permeability of HUVEC monolayer was significantly increased by LPS which was (83.1 ± 1.7)% of control (P < 0.01), however, it was notably inhibited by LXA(4) (P < 0.05); the blockade of FPRL-1 could attenuate the effect of LXA(4), that is, there was no difference between the LPS + LXA(4) + BOC-2 group and the LPS group. (2) After treatment with different concentration of LPS(0, 0.1, 1, 10 mg/L), the mRNA expressions of TNF-α were increased (1.11 ± 0.11, 1.27 ± 0.03, 1.60 ± 0.06, 1.82 ± 0.04, respectively), compared with the control group, at the concentration of 1, 10 mg/L LPS, the difference was statistically significant (P < 0.05). (3) The increased levels of NF-κB and inflammatory mediator TNF-α in the LPS group were both inhibited by LXA(4). Levels of NF-κB protein and TNF-α mRNA secretion in LPS treated group (0.53 ± 0.06 and 0.81 ± 0.09, respectively) were both inhibited by LXA(4)(0.19 ± 0.05 and 0.41 ± 0.07, respectively, and both had significant difference, P < 0.05). (4) Levels of TNF-α in HUVEC culture medium of LPS group [(31.94 ± 0.01) ng/L] was significantly higher than the control group [(18.17 ± 0.03) ng/L, P < 0.05], LPS + LXA(4) group [(15.72 ± 0.07) ng/L] was significantly lower than the LPS group (P < 0.05). CONCLUSION: Our findings demonstrated that LXA(4) could prevent the endothelial cell hyperpermeability induced by LPS in HUVEC under which the possible mechanism was through inhibiting the expression of NF-κB and its related cytokines through receptor-dependent.

Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer.

Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is an active constituent isolated from the root of Rheum palmatum L and is the main effective component of some Chinese herbs and plants. Pharmacological studies have demonstrated that emodin exhibits anti-cancer effects on several human cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. This study was performed to investigate the antiproliferative and antimetastatic effects of emodin on pancreatic cancer in vitro and in vivo. Our results showed that emodin induced a higher percentage of growth inhibition and apoptosis in the pancreatic cancer cell line SW1990 compared to that of control, and emodin suppressed the migration and invasion of SW1990 cells in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and Western blot analysis, and found that emodin significantly down-regulated NF-κB DNA-binding activity, survivin and MMP-9 in SW1990 cells. Moreover, the expression of cleaved caspase-3 was up-regulated in SW1990 cells after treatment with emodin. In addition, a metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into the pancreatic wall of nude mice. Oral administration of emodin significantly decreased tumor weight and metastasis compared to control. Furthermore, the expression of NF-κB, survivin and MMP-9 were also suppressed in tumor tissues after treatment with emodin. Collectively, our results indicated that emodin exerts antiproliferative and antimetastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-κB and its regulated molecules such as survivin and MMP-9 proteins. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human pancreatic cancer.

[Effect of lipoxin A(4) on lipopolysaccharide-induced oxidant stress in human umbilical vein endothelial cells].

OBJECTIVE: To explore the effects of lipoxin A(4) (LXA(4)) on lipopolysaccharide (LPS)-induced oxidative stress in human umbilical veins endothelial cells (HUVEC) and the possible mechanism. METHODS: Neonatal umbilical cords were obtained from normal term pregnant women with cesarean section within 4 hours and then were used to isolate HUVEC for subculture. HUVEC were divided into four groups:control group; LPS group (10 µg/ml of LPS); LPS + LXA(4) group (10 µg/ml of LPS and 100 nmol/L of LXA(4)); LXA(4) group (100 nmol/L of LXA(4)). All expriments were performed after cells treated for 12 and 24 hours respectively. Immunofluorescence was used to detect the expression of VIII foctor and nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2); the mRNA expression of Nrf2, heme oxygenase 1 (HO-1) and reduced form of nicotinamide-adenine dinucleotide quinone oxidoreductase-1 (NQO1) were evaluated by reverse transcription-PCR. RESULTS: (1) The flavovirens fluorescence was observed in the cytoplasm under fluorescence microscope, which confirmed the existence of VIII factor which specifically expressed in endothelial cells, especially in HUVEC. (2) Immunofluorescent results showed that in control group, Nrf2 protein expressed in the cytosol rather than in the nucleus. In LPS group, the expression of Nrf2 protein obviously increased in the nucleus while decreased in the cytosol after 12 hours. However, after LPS treatment for 24 hours, Nrf2 expression reduced in the cytosol and nucleus. In co-treatment with LPS and LXA(4) group, the expression of Nrf2 protein was much higher than that in LPS group after 12 hours or 24 hours. Furthermore, Nrf2 protein also mostly expressed in the cytosol in LXA(4) group. (3) After stimulation for 12 hours, compared with control group, the gene expression of Nrf2 and HO-1 were significantly enhanced in LPS group (0.581 ± 0.019 and 0.081 ± 0.009, P < 0.05) and in LPS + LXA(4) group (0.692 ± 0.048 and 0.136 ± 0.018, P < 0.05), the level of NQO1 mRNA in LPS group and LPS + LXA(4) group were 0.381 ± 0.009 (P > 0.05) and 0.574 ± 0.034 (P < 0.05). After treatment for 24 hours, compared with control goup, the gene expressions of Nrf2 and NQO1 were down-regulated in LPS group (0.180 ± 0.017 and 0.472 ± 0.064, P < 0.05). But in LPS + LXA(4) group the expression of Nrf2 and NQO1 were upregulated (0.532 ± 0.051 and 0.830 ± 0.068, P < 0.05, compared with treatment for LPS group). The mRNA expressions of Nrf2, HO-1 and NQO1 were increased in LPS + LXA(4) group compared with LPS group (P < 0.05). In addition, there was no markedly difference in the expressions of Nrf2, HO-1 and NQO1 between control and LXA(4) group after 12 hours and 24 hours (P > 0.05). CONCLUSION: Through activating nuclear translocation of Nrf2 protein from cytoplasm, LXA(4) upregulates the Nrf2 downstream enzymes, such as NQO1 and HO-1 to protect HUVEC against the oxidative stress induced by LPS.