Sevoflurane attenuates proliferative and migratory activity of lung cancer cells via mediating the microRNA-100-3p/sterol O-Acyltransferase 1 axis.

Recently, evidence has shown that microRNA-100-3p (miR-100-3p) has been revealed as a tumor suppressor in diverse human diseases, while its capability in lung cancer warrants further validation. In this work, we aimed to discuss the impact of sevoflurane on biological functions of lung cancer cells by modulating the miR-100-3p/sterol O-acyltransferase 1 (SOAT1) axis. Lung cancer cell lines (A549 and H460) were treated with various concentrations of sevoflurane. Cell viability, proliferation, migration, and invasion were evaluated using MTT, colony formation, wound healing, and transwell assays. Moreover, miR-100-3p and SOAT1 expressions were evaluated by reverse transcription-quantitative polymerase chain reaction in lung cancer cells. The target interaction between miR-100-3p and SOAT1 was predicted by bioinformatics analysis and verified by the dual-luciferase reporter gene assay. The findings of our work demonstrated that sevoflurane impeded the abilities on viability, proliferation, migration, and invasion of A549 and H460 cells. The expression of miR-100-3p was reduced, and SOAT1 expression was elevated in lung cancer cells. miR-100-3p targeted SOAT1. Besides, sevoflurane could lead to expressed improvement of miR-100-3p or limitation of SOAT1. Downregulation of miR-100-3p or upregulation of SOAT1 restored the suppression of sevoflurane on abilities of viability, proliferation, migration, and invasion in A549 and H460 cells. In the rescue experiment, downregulation of SOAT1 reversed the impacts of downregulation of miR-100-3p on sevoflurane on lung cancer cells. Collectively, our study provides evidence that sevoflurane restrained the proliferation and invasion in lung cancer cells by modulating the miR-100-3p/SOAT1 axis. This article provides a new idea for further study of the pathogenesis of lung cancer.

Comparison of the clinical efficacy of a femoral neck system versus cannulated screws in the treatment of femoral neck fracture in young adults.

BACKGROUND: To compare the clinical efficacy of a femoral neck system (FNS) and cannulated screws (CS) in the treatment of femoral neck fracture in young adults. METHODS: Data from 69 young adults, who were admitted for femoral neck fracture between March 2018 and June 2020, were retrospectively analyzed. Patients were divided into two groups according to surgical method: FNS and CS. The number of intraoperative fluoroscopies, operative duration, length of hospital stay, fracture healing time, Harris score of hip function, excellent and good rate of hip function, and postoperative complications (infection, cut out the internal fixation, nail withdrawal, and femoral neck shortening) were compared between the two groups. Hip joint function was evaluated using the Harris Hip Scoring system. RESULTS: All 69 patients had satisfactory reduction and were followed up for 12-24 months, with a mean follow-up of 16.91 ± 3.01 months. Mean time to fracture healing was13.82 ± 1.59 and 14.03 ± 1.78 weeks in the FNS and CS groups, respectively. There was a statistical difference in the number of intraoperative fluoroscopies between the 2 groups (P = 0.000). There were no significant differences, in operation duration, hospital length of stay, fracture healing time, complications, Harris Hip Score for hip function and excellent and good rate between the two groups (P > 0.05). The incidence of complications was 6.1%(2/33) in the FNS group lower than 25%(9/36) in the CS group, a difference that was statistically significant (P = 0.032). At the last follow-up, the Harris Hip Score of the hip joint in the FNS group was 90.42 ± 4.82and 88.44 ± 5.91 in the CS group. CONCLUSIONS: Both treatment methods resulted in higher rates of fracture healing and excellent hip function. Compared with CS, the FNS reduced the number of intraoperative fluoroscopies, radiation exposure to medical staff and patients, and short-term complications including femoral neck shortening and bone nonunion.

circMTDH.4/miR-630/AEG-1 axis participates in the regulation of proliferation, migration, invasion, chemoresistance, and radioresistance of NSCLC.

Astrocyte elevated gene-1 (AEG-1) plays a critical role in the development, progression, and metastasis of a variety of cancers, including non-small-cell lung cancer (NSCLC). The objective of the current study is to unravel the upstream signaling of AEG-1. A cohort of 28 NSCLC tissues and 30 normal tissues were collected. Quantitative reverse transcription-polymerase chain reaction and Western blotting were used to examine AEG-1, migration, and invasion related markers in NSCLC cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay coupled with colony formation assay were conducted to monitor cell growth. Transwell assay was performed to determine cell migration and invasion. Apoptotic cells were detected by costaining with Annexin-V-fluorescein isothiocyanate and propidium iodide. Immunofluorescent staining was used to observe the levels of migration and invasion related markers. Xenograft models were used to investigate tumor formation in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation were carried out to determine the interaction between circMTDH.4 and miR-630, as well as the associated between miR-630 and AEG-1. AEG-1 was highly expressed in NSCLC tissues and cell lines. Silencing of AEG-1 inhibited cell proliferation, migration, invasion, and chemoresistance/radioresistance in NCI-H1650 and A549 cells. circMTDH.4 regulated AEG-1 expression via sponging miR-630. Knockdown of circMTDH.4 and/or overexpression of miR-630 inhibited chemoresistance and radioresistance in NSCLC cells, whereas overexpression of AEG-1 or knockdown of miR-630 exerted rescue effects. circMTDH.4/miR-630/AEG-1 axis is responsible for chemoresistance and radioresistance in NSCLC cells.

Tibial shaft fractures treated with intramedullary nailing and reduction device assistance.

PURPOSE: This study aimed to assess the outcomes of a newly invented reduction device on assisting reduction of intramedullary nailing (IMN) in the treatment of tibial shaft fractures. METHODS: From January 2015 to December 2018, data of patients with tibial shaft fractures treated with IMN were reviewed. In total, 42 patients underwent treatment with the new reduction device (group A) and 56 underwent treatment using a traditional reduction technique (group B). Data related to the closed reduction rate, surgical time, blood loss, number of fluoroscopies, number of surgeons, and number of complications were also reviewed. Fracture healing was assessed using radiographs at each follow-up, and the functional outcome (AOFAS score) was evaluated at the final follow-up. RESULTS: The two treatment groups were evenly matched with respect to age, sex, fracture grade, and time to surgery. The average surgical time, blood loss, number of fluoroscopies, and number of surgeons in group A were all lesser than those in group B (P < 0.05). The closed reduction rate in group A was higher than those in group B (P < 0.05). The fracture healing time, AOFAS score, and complication rate were not significantly different (P > 0.05) between the two groups. CONCLUSION: The new reduction device could effectively achieve and maintain the reduction of tibia shaft fractures in a minimally invasive fashion.

Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth.

BACKGROUND/AIMS: Assistance with tumor-associated vascularization is needed for the growth and invasion of non-small cell lung cancer (NSCLC). Recently, it was shown that placental growth factor (PLGF) expressed by NSCLC cells had a critical role in promoting the metastasis of NSCLC cells. However, the underlying molecular mechanisms remain elusive. METHODS: Here, we first established a NSCLC model in mice that allows us not only to isolate tumor cells from non-tumor cells in the tumor, but also to trace tumor cells in living animals. Levels of PLGF, its unique receptor Flt-1, as well as transforming growth factor ß1 (TGFß1) was examined in tumor cells and tumor-associated macrophages (TAM) by RT-qPCR. A transwell well co-culture system and HUVEC assay were applied to study the crosstalk between NSCLC cells and TAM. RESULTS: NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through surface expression of Flt-1 on macrophages. In a transwell co-culture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete TGFß1 to enhance the growth of endothelial cells in a HUVEC assay. CONCLUSION: The cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFß receptor signaling may promote the growth and vascularization of NSCLC.

Musashi1 Promotes Non-Small Cell Lung Carcinoma Malignancy and Chemoresistance via Activating the Akt Signaling Pathway.

BACKGROUND/AIMS: Lung cancer is one of the leading causes for cancer mortality. The poor therapeutic outcome of non-small cell lung carcinoma (NSCLC) is mainly due to late diagnosis and chemoresistance. In this study, we investigated the role of Musashi1 (MSI1) in NSCLC malignancy and chemoresistance. METHODS: Colony formation, MTT, glucose uptake and lactate production assays were employed to study lung cancer cell malignancy and chemoresistance. RT-PCR and Western blotting were performed to detect mRNA and protein expressions of genes. We used immunohistochemistry and Pearson correlation analysis to study the relationship of gene expression. RESULTS: We demonstrated that MSI1 was able to promote the proliferation and glucose metabolism of NSCLC cells, and to mediate the sensitivity to chemotherapy drugs in NSCLC cells. Importantly, we found that MSI1 could regulate the activity of Akt signaling. The regulation of NSCLC proliferation, glucose metabolism and chemoresistance by MSI1 was dependent on the modulation of the activity of the Akt signaling pathway. We also found that MSI1 was a target of miR-181a-5p, a microRNA involved in the regulation of cancer development. The expression levels of MSI1 and miR-181a-5p were negatively correlated in NSCLC. CONCLUSION: MSI1 promotes non-small cell lung carcinoma malignancy and chemoresistance via activating the Akt signaling pathway, which provides a new strategy for the therapy of NSCLC.

Arsenic trioxide potentiates the anti-cancer activities of sorafenib against hepatocellular carcinoma by inhibiting Akt activation.

Sorafenib is the standard first-line systemic drug for advanced hepatocellular carcinoma (HCC), but it also induces the activation of Akt, which contributes to the mechanisms for the resistance to sorafenib. Arsenic trioxide (ATO) is a currently clinically used anticancer drug and displays its anticancer activities by inhibiting Akt activation. Therefore, we hypothesized that ATO may potentiate the anti-cancer activities of sorafenib against HCC. The results have demonstrated that ATO synergized with sorafenib to inhibit the proliferation and promote the apoptosis of HCC cells by diminishing the increased activation of Akt by sorafenib. ATO was shown to inhibit the expression or activation of Akt downstream factors, including glycogen synthase kinase (GSK)-3ß, mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which regulate cell apoptosis and were upregulated or activated by sorafenib. Both sorafenib and ATO downregulated the expression of cyclin D1, resulting in HCC cells arrested at G0/G1 phase. ATO downregulated the expression of Bcl-2 and Bcl-xL and upregulated the expression of Bax, indicating that ATO could induce the apoptosis of HCC cells through the intrinsic pathways; but sorafenib showed little effects on these proteins of Bcl-2 family. ATO synergized with sorafenib to suppress the growth of HCC tumors established in mice by inhibiting the proliferation and inducing the apoptosis of HCC cells in situ. These results indicate that ATO may be a potential agent that given in combination with sorafenib acts synergistically for treating HCC.

New insights into the effect of pyrolysis temperature on the spectroscopy properties of dissolved organic matter in manure-based biochar.

Dissolved organic matter (DOM) derived from biochar takes a crucial role in transport and bioavailability toward contaminants; hence, it is undeniable that a thorough analysis of its properties is important. So far, the effect of pyrolysis temperature on the functional groups, components, and evolutionary sequence of manure-based biochar DOM has not been adequately investigated. Here, DOM was released from two typical livestock manures (cow and pig) at five pyrolysis temperatures (300 ~ 700°C), and it was explored in depth with the aid of moving window 2D correlation spectroscopy (MW-2D-COS) and heterogeneous 2D correlation spectroscopy (hetero-2D-COS). The results demonstrated that the concentration, aromaticity, and hydrophobicity of DOM were greater at high temperatures, and more DOM was liberated from cow manure-based biochar at identical temperature. Protein-like compounds dominated at high temperatures. The pyrolysis temperatures of final configuration transformation points of the fulvic acid-like component and the aromatic ring C=C in DOM were 400°C and 500°C, respectively. Moreover, Fourier transform infrared spectroscopy combined with two-dimensional correlation analysis indicated that the functional group evolution of DOM depends on the pyrolysis temperature and feedstock type. The study provides a new perspective on manure management and environmental applications of biochar.

The Role of Triboloading Conditions in Tribolayer Formation and Wear Resistance of PES-Based Composites Reinforced with Carbon Fibers.

In this paper, the tribological characteristics of polyethersulfone-based composites reinforced with short carbon fibers (SCFs) at aspect ratios of 14-250 and contents of 10-30 wt.% are reported for linear metal-polymer and ceramic-polymer tribological contacts. The results showed that the wear resistance could be greatly improved through tribological layer formation. Loading PES with 30 wt.% SCFs (2 mm) provided a minimum WR value of 0.77 × 10-6 mm3/N m. The tribological layer thicknesses were estimated to be equal to 2-7 µm. Several conditions were proposed, which contributed to the formation of a tribological layer from debris, including the three-stage pattern of the changing kinetics of the time dependence of the friction coefficient. The kinetics had to sharply increase up to ~0.4-0.5 in the first (running-in) stage and gradually decrease down to ~0.1-0.2 in the second stage. Then, if these levels did not change, it could be argued that any tribological layer had formed, become fixed and fulfilled its functional role. The PES-based composites loaded with SCFs 2 mm long were characterized by possessing the minimum CoF levels, for which their three-stage changing pattern corresponded to one of the conditions for tribological layer formation. This work provides valuable insight for studying the process parameters of tribological layer formation for SCF-reinforced thermoplastic PES composites and revealing their impact on tribological properties.

Biomechanical evaluation of Gamma 3 nail with anti-rotation screw fixation for unstable femoral neck fractures: a biomechanical study.

This study aims to evaluate the biomechanical performance of the Gamma 3 nail with an anti-rotation screw (GNS) and compare it to two established gold-standard methods for treating unstable femoral neck fractures (UFNFs). Synthetic bone models were prepared with Pauwels' type III osteotomy and an additional posterior wedge. Three different implant configurations were tested: three cannulated crews (3CS) in an inverted triangle configuration, a dynamic hip screw with an anti-rotation screw (DHSS), and GNS. Non-destructive cyclic axial loading was applied at 7° adduction, with 1000 cycles ranging from 100 to 1000 N. Subsequently, a construct failure test was conducted using progressive axial compression, and fracture reduction loss was recorded. The average axial stiffness was 321 ± 52 N/mm for 3CS, 430 ± 71 N/mm for DHSS, and 519 ± 104 N/mm for GNS. The average ultimate failure loads were 2699.3 N for 3CS, 3427.1 N for DHSS, and 3758.9 N for GNS. GNS demonstrated significantly greater axial stiffness compared to the other two groups (P < 0.05). Both DHSS and GNS exhibited similar failure loading, which were greater than those of 3CS (P < 0.05). GNS offers the advantages of a minimally invasive and intramedullary implant with comparable stability to the DHSS system. Moreover, GNS demonstrated superior biomechanical performance compared to 3 CS configuration.

Binding characteristics of Pb and Zn to low-temperature feces-based biochar-derived DOM revealed by EEM-PARAFAC combined with general and moving-window two-dimensional correlation analyses.

Pyrolysis carbonization of human feces has shown potential for converting feces biomass into a soil amendment. However, little is known about the interactions of DOM derived from feces-based biochar produced at low-temperature with heavy metals (HMs). In this study, the binding properties of Pb(II) and Zn(II) with DOM derived from feces-based biochar produced at low pyrolysis temperatures were investigated using EEM-PARAFAC combined with general, and moving-window two-dimensional correlation analyses (2D-COS). The results revealed that DOM from biochar produced at 280 °C exhibited a higher Pb(II) and Zn(II) affinity and more binding sites than DOM produced at 380 °C. The fulvic-like and humic-like components exhibited obvious fluorescence quenching after the heavy metal addition, and the complexes formed with Pb(II) and Zn(II) were more stable. C-H groups exhibited the fastest response to Pb(II) and Zn(II) binding in the FB280 DOM, while the COO- groups of carboxylic acids in the FB380 DOM exhibited the fastest response to Pb(II) and Zn(II). Moreover, the mutation concentration range of components and functional groups in DOM, as analyzed by MW2D-COS, was greater for Zn(II) than for Pb(II). These results provide a more detailed molecular-level understanding of the interaction mechanisms between heavy metals and feces-based biochar-derived DOM and the effect of HM concentration on DOM binding. Further, these results will help to provide a reasonable reference for feces management and feces-based biochar in controlling soil HMs.

Optical properties, bioimaging and theoretical calculation of a Zn(II) complex based on triphenylamine derivative.

A luminescent material with various optical properties based on a triphenylamine Zn(II) complex is described. The ultraviolet-visible absorption, one-photon excited fluorescence (OPEF) and two-photon excited fluorescence (TPEF) of the complex indicate that the material has good OPEF and TPEF properties. And the results of one- and two-photon HepG2 cells imaging experiments show the potential of the complex in fluorescence microscopy bioimaging. The experimental Stokes shift and the FWHM (full-width at half-maximum) in different solvents were correlated with the rMPI polarity of the solvent, and the perfect Boltzmann curves were obtained, where the Boltzmann correlation between Stokes shift and solvent polarity is reported for the second time. But the Boltzmann correlation between FWHM and solvent polarity is reported for the first time. In addition, the computational results indicate that, the covalent bond within the salt ZnBr2 is strengthened by the coordination, and the newly formed coordination bond Zn-N is stronger than the original covalent bond Zn-Br.

Downregulating hypoxia-inducible factor-2α improves the efficacy of doxorubicin in the treatment of hepatocellular carcinoma.

The hypoxic microenvironment inside solid tumors, including hepatocellular carcinoma (HCC), is a major cause of tumor resistance to chemotherapy. The recently identified hypoxia-inducible factor (HIF)-2 executes the hypoxia response. Its expression feature and transcriptional targets indicate a possible dominance of HIF-2 in regulating genes in HCC. The aim of the present study was to determine whether transfection of siRNA targeting HIF-2α could enhance the efficacy of doxorubicin, the most commonly used drug in the treatment of HCC. Transfection of HIF-2 siRNA into human HCC cells downregulated the expression of HIF-2α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-α, and cyclin D1, but had little effect on the expression of HIF-1α, fms-related tyrosine kinase-1 (Flt-1), the glucose transporter (GLUT)-1, and lactate dehydrogenase A (LDHA). Doxorubicin itself only downregulated VEGF expression. Furthermore, HIF-2 siRNA inhibited proliferation, induced cell cycle arrest at the G(0)/G(1) phase, and acted synergistically with doxorubicin to inhibit the growth of human HCC cells in vitro. Transfection of HIF-2 siRNA also downregulated tumoral expression of HIF-2α, VEGF, TGF-α, and cyclin D1 in vivo, and acted synergistically with doxorubicin to suppress the growth of HepG2 tumors established in immunodeficient mice by inhibiting cell proliferation, tumor angiogenesis and microvessel perfusion. The results of the present study suggest that targeting HIF-2α with siRNA warrants investigation as a potential strategy to enhance the efficacy of doxorubicin in the treatment of HCC.

Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin inhibits hepatic metastasis of colon cancer.

Liver metastasis is the major obstacle for prolonging the survival of colon cancer patients. Low-molecular-weight heparin (LMWH), a common drug for venous thromboembolism, has displayed beneficial effects in improving the survival of cancer patients, though the mechanism remains unclear. This study aimed to investigate the effects of LMWH on hepatic metastasis of colon cancer and its underlying molecular mechanism by targeting the interaction of the chemokine receptor CXCR4 and its ligand CXCL12 (formerly known as stromal cell-derived factor 1α, SDF-1α), as the CXCR4-CXCL12 axis has been shown to regulate the interaction of cancer cells and stroma. Experimental results revealed that LMWH (Enoxaparin, 3500-5500 Da) inhibited the CXCL12-stimulated proliferation, adhesion and colony formation of human colon cancer HCT-116 cells that highly expressed CXCR4. Interestingly, LMWH or an anti-CXCR4 blocking antibody diminished the migrating and invading abilities of HCT116 cells stimulated by the recombinant CXCL12 protein or liver homogenates which contained endogenous CXCL12 protein. Although LMWH did not significantly inhibit the growth of subcutaneous colon tumors, it significantly suppressed the formation of hepatic metastasis established by intrasplenic injection of colon cancer cells in nude Balb/c mice and also downregulated the expression of CXCL12 in hepatic sinusoidal endothelial cells. The results suggest that LMWH inhibits the formation of hepatic metastasis of colon cancer by disrupting the interaction of CXCR4 and CXCL12, supporting that perioperative administration of LMWH may help to prevent the seeding and subsequent growth of hepatic metastases of colon cancer cells.

Hydrogen sulfide protects cardiomyocytes from myocardial ischemia-reperfusion injury by enhancing phosphorylation of apoptosis repressor with caspase recruitment domain.

Hydrogen sulfide (H(2)S) displays an anti-apoptotic activity against myocardial ischemia reperfusion (MIR). Apoptosis repressor with caspase recruitment domain (ARC) is constitutively expressed in the heart and inhibits cell apoptosis when it is phosphorylated. Here, we investigated whether H(2)S could inhibit apoptosis by affecting ARC phosphorylation using cultured rat cardiomyocytes and a rat model of MIR. Primary cardiomyocytes were prepared from hearts of newborn rats and were pre-incubated with NaHS, a donor of H(2)S, for 60 min. Cardiomyocytes were subjected to hypoxia for 4 h, followed by reoxygenation for 2 h. The hypoxia and subsequent reoxygenation (H/R) significantly induced cell apoptosis, increased expression levels of Fas and FasL proteins, enhanced release of cytochrome c from mitochondria, and elevated caspase-3 activity, while H/R reduced ARC phosphorylation and increased the activity of calcineurin that dephosphorylates ARC. Pre-incubation with NaHS significantly attenuated the above effects through promoting ARC phosphorylation by reducing calcineurin activity and by increasing the activity of protein kinase casein kinase II (CK2) that phosphorylates ARC. In fact, TBB, a specific inhibitor of CK2, abolished the effects of NaHS. In rats undergoing MIR, NaHS significantly reduced the myocardial infarct size, cell apoptosis, calcineurin activity, and the expression levels of Fas, FasL and cleaved caspase-3 proteins, while NaHS increased ARC phosphorylation. In contrast, DL-propargylglycine, an inhibitor of cystathionine γ-lyase, the main enzyme for H(2)S production in hearts, showed opposite effects to NaHS. The results indicate that H(2)S inhibits apoptosis of cardiomyocytes induced by MIR through enhancing ARC phosphorylation.

The inhibitory role of b7-h4 in antitumor immunity: association with cancer progression and survival.

B7-H4 is one of the most recently identified members of B7 superfamily of costimulatory molecules serving as an inhibitory modulator of T-cell response. B7-H4 is broadly expressed in human peripheral tissues and inducibly expressed in immune cells. The expression of B7-H4 has been observed in various types of human cancer tissues, and its soluble form has been detected in blood samples from cancer patients. However, its precise physiological role is still elusive, as its receptor has not been identified and the expression levels are not consistent. This paper summarizes the pertinent data on the inhibitory role of B7-H4 in antitumor immunity and its association with cancer progression and survival in human patients. The paper also discusses the clinical significance of investigating B7-H4 as potential markers for cancer diagnosis and prognosis, and as therapeutic targets.

PIGF and Flt-1 on the surface of macrophages induces the production of TGF-ß1 by polarized tumor-associated macrophages to promote lung cancer angiogenesis.

BACKGROUND: The interaction between tumor cells and tumor microenvironment is a necessary condition for promoting the metastasis of malignant tumors. METHODS: Two different transwell culture systems were interfered with by recombinant factor placental growth factor (re-PIGF) and the re-PIGF + transforming growth factor-ß1 (TGF-ß1)-neutralizing antibody (anti-TGF-ß1). We performed immunofluorescence, flow cytometry and enzyme linked immunosorbent assay (ELISA) to analyze the expression of PIGF, fms-like tyrosine kinase-1 (Flt-1), macrophage marker F4/80 +, macrophage M2 marker CD163+ and TGF-ß1 in vitro. Meanwhile, cell viability assay and optical microscope assay were conducted to explore the cell viability and vascularization ability of human umbilical vein endothelial cells (HUVECs). RESULTS: Re-PIGF increased the expression of PIGF in A549 cells and the expression of Flt-1 in BM-Mac cells, and significantly enhanced the ability of bone marrow-derived macrophages (BM-Mac) to transform into macrophages. At the same time, re-PIGF increased the expression of cytokine TGF-ß1 in A549 cells/BM-Mac transwell culture system. On the contrary, re-PIGF + anti-TGF-ß1 inhibited the expression of Flt-1 in BM-Mac cells and inhibited the ability of BM-Mac cells to transform into macrophages. Finally, re-PIGF + anti-TGF-ß1 reduced the cell viability and angiogenesis of HUVECs. CONCLUSION: The surface molecule PIGF of lung cancer cells could bind to the receptor Flt-1 on the surface of macrophages, thereby increasing the production of TGF-ß1, and ultimately promoting the formation of angiogenesis in lung cancer.

Prediction of Pleural Invasion in Challenging Non-Small-Cell Lung Cancer Patients Using Serum and Imaging Markers.

Introduction. Preoperative detection of pleural invasion in lung cancer patients is key to curative surgical treatment. We tried to predict pleural invasion in non-small-cell lung cancer patients with <100 ml pleural fluid. METHODS: Patients admitted from August 1, 2011, to December 31, 2018, were retrospectively retrieved. Records of serum and imaging markers were analyzed. RESULTS: Among 7004 patients who received surgery, 43 cases with <100 ml pleural fluid who had pleural invasion were included, and another 108 cases without pleural invasion were enrolled as controls. There were no differences in squamous cell carcinoma antigen (SCC) or neuron-specific enolase (NSE) values between the pleural invasion and noninvasion groups (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (. CONCLUSIONS: Serum CEA and CYFRA21-1, location of original lung cancer (right mid lobe), maximum diameter, CT-detectable pleural fluid, pleural sign by CT, and PET/CT-predicted pleural invasion were good markers for the prediction of pleural invasion in non-small-cell lung cancer patients.

microRNA-877 contributes to decreased non-small cell lung cancer cell growth via the PI3K/AKT pathway by targeting tartrate resistant acid phosphatase 5 activity.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death in both men and women. microRNAs (miRs) can exert important functions in cancer development. However, the role of miR-877 in NSCLC as it relates to tartrate resistant acid phosphatase 5 (ACP5) is unknown. For this study, the gain-and-loss-of-function experiments were performed to explore the effects of miR-877 and ACP5 on NSCLC. miR-877 expression in LC and paracancerous tissues, lung epithelial cell line and NSCLC cell lines was detected, and the association between miR-877 expression and clinical features of LC patients was analyzed. The levels of ACP5, epithelial-mesenchymal transition (EMT) markers and apoptosis-related proteins were measured. In vivo experiments were conducted for further validation. Consequently, we found that miR-877 expression was lowered in LC tissues and cell lines, and correlated with clinical stage, differentiation, lymph node metastasis and prognosis of NSCLC patients. Additionally, miR-877 was determined to inhibit ACP5 activity, and miR-877 downregulated the PI3K/AKT pathway by silencing ACP5. Furthermore, overexpression of miR-877 inhibited the viability, migration, invasion and EMT of NSCLC cells, but promoted cell apoptosis. In conclusion, miR-877 overexpression inhibited malignant biological behaviors of NSCLC cells by downregulating ACP5 and inactivating the PI3K/AKT pathway.

LncRNA TTN-AS1 promotes the progression of cholangiocarcinoma via the miR-320a/neuropilin-1 axis.

Neuropilin-1 regulated by miR-320a participates in the progression of cholangiocarcinoma by serving as a co-receptor that activates multiple signaling pathways. The present study sought to investigate upstream lncRNAs that control the expression of miR-320a/neuropilin-1 axis and dissect some of the underlying mechanisms. Here we report lncRNA TTN-AS1 (titin-antisense RNA1) acts as a sponging ceRNA to downregulate miR-320a and is highly expressed in human cholangiocarcinoma tissues and cells. The expression of the above three molecules is correlated with the clinicopathologic parameters of cholangiocarcinoma patients. In this study, multiple bioinformatics tools and databases were employed to seek potential lncRNAs that have binding sites with miR-320a and TTN-AS1 was identified because it exhibited the largest folds of alteration between cholangiocarcinoma and normal bile duct epithelial cells. The regulatory role of TTN-AS1 on miR-320a was further evaluated by luciferase reporter and RNA pulldown assays, coupled with in situ hybridization and RNA immunoprecipitation analyses, which showed that TTN-AS1 bound to miR-320a through an argonaute2-dependent RNA interference pathway in the cytoplasm of cholangiocarcinoma cells. Knockdown and overexpression assays showed that the regulatory effect between TTN-AS1 and miR-320 was in a one-way manner. TTN-AS1 promoted the proliferation and migration of cholangiocarcinoma cells via the miR-320a/ neuropilin-1 axis. The function of TTN-AS1 on tumor growth and its interaction with miR-320a were confirmed in animal models. Further mechanistic studies revealed that TTA-AS1, through downregulating miR-320a, promoted cell cycle progression, epithelial-mesenchymal transition, and tumor angiogenesis by upregulating neuropilin-1, which co-interacted with the hepatocyte growth factor/c-Met and transforming growth factor (TGF)-ß/TGF-ß receptor I pathways. In conclusion, the present results demonstrate that lncRNA TTA-AS1 is a sponging ceRNA for miR-320a, which in turn downregulates neuropilin-1 in cholangiocarcinoma cells, indicating these three molecules represent potential biomarkers and therapeutic targets in the management of cholangiocarcinoma.