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Background: Small Cell Lung Cancer (SCLC) represents the most aggressive pulmonary neoplasm and is often diagnosed at late stage with limited survival, despite combined chemotherapies. The purpose of this study was to investigate the effect of anlotinib on SCLC and the potential molecular mechanisms. Methods: Cell viability was assessed by CCK-8 assay to determine the adequate concentration of anlotinib. Then, effects of anlotinib on cell apoptosis, cell cycle distribution, migration and invasion were analyzed by flow cytometry, PI staining, wound healing assay and transwell assay, respectively. The protein expression of c-met and ERK1/2 pathways in H446 cells were assessed by western blot analysis. Result: In this study, we found that anlotinib significantly reduced the cell viability of H446 cells, induced G2/M cell cycle arrest and decreased invasion and migration of H446 cells. Futhermore, we also found that anlotinib could suppress c-met signal transduction and activate the ERK1/2 pathway in H446 cells. More importantly, c-met was involved in the effects of anlotinib on migration and invasion in H446 cells. Conclusion: Taken together, our results demonstrated that anlotinib was a potential anticancer agent that inhibited cell proliferation, migration and invasion via suppression of the c-met pathway and activation of the ERK1/2 pathway in H446 cells.

Introduction: The roles of some indicators in the prognosis of patients with coronavirus disease-19 (COVID-19) remain unclear and controversial. This study aimed to explore the epidemiologic characteristics of and prognostic factors for COVID-19 to provide updated recommendations for its prevention, diagnosis, and treatment.Methods: For this retrospective study, demographic, epidemiologic, and clinical data were extracted from the medical records of patients admitted to the Maternal and Child Hospital of Hubei Province (Optical Valley) with COVID-19 between February 19, 2020, and March 19, 2020. The primary outcome was the prognosis that was determined at discharge as mentioned in the medical records. Descriptive statistics, univariate analyses, and stepwise logistic regression analysis were used for data analysis.Results: Of the 1,765 patients included, 93.1% were cured and the mortality was 1.8%. Univariate analyses identified 63 factors significantly associated with COVID-19 prognosis. Logistic regression analysis revealed that a poorer prognosis was associated with undergoing resuscitation, complex disease manifestations, consultation with outside specialists, elevated basophil or lymphocyte counts, an albumin (ALB)/globulin (A/G) ratio > 2.4, and elevated levels of serum aspartate aminotransferase (AST) or creatinine. Patients had a better prognosis if the following conditions were met: dry cough reported as an initial symptom, fatigue as a clinical manifestation, and a diagnosis based on laboratory testing.Conclusion: To prevent clinical deterioration, clinicians should provide special care to patients who underwent resuscitation, with a critical disease, or requiring consultation with outside specialists. Extra attention should be paid to patients with high basophil or lymphocyte counts, a high A/G ratio, and elevated AST or creatinine levels.

BackgroundHepatic Stellate Cell (HSC) represents a key factor in liver fibrosis. Early-stage liver fibrosis is still reversible and is intimately associated with the state of HSC. KLF4 has been shown to play a pivotal role in a wide array of physiological and pathological processes. MethodsIn this study, we examined the effect of Kruppel-like factor 4 (KLF4) on the proliferation, apoptosis and phenotype of HSC in resting state in human HSC LX-2 cells, and the role KLF4 plays in the maintenance of the resting state of HSC, with an attempt to provide an experimental basis for the diagnosis, treatment and prognosis evaluation of liver fibrosis. We designed a KLF4 lentiviral vector and a KLF4 shRNA lentiviral vector, to up-regulate and silence KLF4 expression in LX-2 cells by transfection. We examined LX-2 cell proliferation by plate cloning and CCK8 assay, flow cytometrically detected cell cycle distribution and cellular apoptosis rate and determined some quiescence and activation markers of HSC by Western blotting. ResultsOur result showed that E-cadherin and ZO-1, dubbed quiescent HSC markers, were significantly increased. N-cadherin while a-AMA, known as activated HSC marker, was significantly decreased. In contrast, cell proliferation and apoptosis rate were elevated in LX-2 cells whose KLF4 expression had been silenced. Conclusions Our results indicated that KLF4 inhibited the proliferation and activation of human HSC LX-2 and might be a key regulatory protein in the maintenance of quiescence of HSC and might serve as a target for the inhibition of hepatic fibrosis.

The exocyst, an evolutionarily conserved octomeric protein complex, has been demonstrated as an essential component for vesicle tethering during cell exocytosis, and participates in various physiological processes in the cell. Although subunits of the exocyst complex have been reported to be involved in the regulation of TGF-β induced cancer cell migration and epithelial-mesenchymal transition (EMT), the potential function of Sec3 in these regulated processes remains unclear. Here, we show that Sec3 knockdown abolishes TGF-β stimulated A549 lung cancer cell migration in vitro and causes defects in the regulated EMT process. In addition, we find that depletion of Sec3 significantly inhibits TGF-β stimulated Akt phosphorylation in A549 cells, whereas the increase of Smad2 phosphorylation is unaffected. Furthermore, replenishment of an RNAi-resistant form of Sec3 is shown to restore the defects of TGF-β induced cell migration, EMT and Akt signaling activation. In summary, our study provides evidence that Sec3 is involved in TGF-β induced cell migration and EMT processes, presumably through the regulation of PI3K/Akt signaling activation in A549 cancer cells.

Objective To explore the protective function of vitamin D (VD)/vitamin D receptor (VDR) on the development of oral lichen planus (OLP) and elaborate the underling mechanism of it. Methods H&E staining, myeloid Peroxidase (MPO) assays, quantitative PCR (qPCR), western blotting and Elisa were used to test the human biopsies and serum. QPCR, western blotting, Elisa and siRNA transfection were also performed in LPS-induced keratinocytes to observe the functions of vitamin D and VDR. Results The lack of VDR in the diseased biopsies from OLP patients was associated with activated helper T-cell type 1 (Th1)-driven inflammatory response. Importantly, the status of serum 25-hydroxyvitamin D of OLP patients was reduced consistently. In a cultured cell model, 1,25(OH)2D3 could downregulate excessive production of pro-inflammatory factors induced by lipopolysaccharide (LPS) in keratinocyte HaCat cells. Mechanistically, even though LPS-induced cytokines in keratinocytes were inhibited both by nuclear factor-κB (NF-κB) inhibitor and by activator protein 1 (AP-1) inhibitor, VDR-dependent 1,25(OH)2D3 blocked the activation of phosphorylated-NF-κB p65 rather than c-Jun/c-Fos in the presence of LPS stimulation. Conclusion These results suggest that 1,25(OH)2D3 plays an anti-inflammatory role in OLP by mediating NF-κB signaling pathway but not AP-1 signaling pathway with a VDR-dependent manner, predicting vitamin D supplement may be a potential strategy for the OLP management. This article is protected by copyright. All rights reserved.

Background: Diabetes Mellitus (DM) accelerates progress of lung cancer. Hyperglycemia, a critical feature of DM, promotes lung cancer metastasis. Mogroside V is a triterpenoid glycoside from Siraitia grosvenorii. Interestingly, mogroside V not only plays an anti-diabetic role, but also has anti-tumor effects. Objective: In this study, we investigated the metastatic efficiency of mogroside V in lung cancer cells cultured in hyperglycemia. Methods: Two lung cancer cell lines-A549 and H1299 were cultured in normoglycemia (5.5mM glucose) and hyperglycemia (25mM glucose). Cellular proliferation was tested by MTT, invasion was examined by transwell assay, migration was measured by wound healing assay, cytoskeleton was stained by Phalloidin-TRITC and the expressions of EMT markers and Rho-GTPase family protein were detected by western blot. Results: Hyperglycemia promoted the invasion and migration of A549 and H1299 cells compared with normoglycemia. Mogroside V inhibited the hyperglycemia-induced invasion and migration. Hyperglycemia promoted epithelial-mesenchymal transition (EMT), while mogroside V could reverse this process through up-regulating E-Cadherin expression and down-regulating N-Cadherin, Vimentin, Snail expressions. Furthermore, mogroside V fractured microfilaments and reduced Rho A, Rac1, Cdc42 and p-PAK1 expressions under hyperglycemic conditions. Conclusion: These results suggest that mogroside V inhibits hyperglycemia-induced lung cancer cells migration and invasion through reversing EMT and damaging cytoskeleton.

Epithelial-mesenchymal transition (EMT) is one of the most important mechanisms in the initiation and promotion of cancer cell metastasis. The phosphoinositide 3-kinase (PI3K) signaling pathway has been demonstrated to be involved in TGF-β induced EMT, but the complicated TGF-β signaling network makes it challenging to dissect the important role of PI3K on regulation of EMT process. Here, we applied optogenetic controlled PI3K module (named ‘Opto-PI3K’), which based on CRY2 and the N-terminal of CIB1 (CIBN), to rapidly and reversibly control the endogenous PI3K activity in cancer cells with light. By precisely modulating the kinetics of PI3K activation, we found that E-cadherin is an important downstream target of PI3K signaling. Compared with TGF-β treatment, Opto-PI3K had more potent effect in down-regulation of E-cadherin expression, which was demonstrated to be regulated in a light dose-dependent manner. Surprisingly, sustained PI3K activation induced partial EMT state in A549 cells that is highly reversible. Furthermore, we demonstrated that Opto-PI3K only partially mimicked TGF-β effects on promotion of cell migration in vitro. These results reveal the importance of PI3K signaling in TGF-β induced EMT, suggesting other TGF-β regulated signaling pathways are necessary for the full and irreversible promotion of EMT in cancer cells. In addition, our study implicates the great promise of optogenetics in cancer research for mapping input-output relationships in oncogenic pathways.

Maleated poly(propylene carbonate) (PPC-MA)/organo-montmorillonite (OMMT) nanocomposites were first prepared via melt end-capping poly(propylene carbonate) (PPC) with maleic anhydride (MA) and melt-mixing the PPC-MA with commercial OMMT without and with hydroxyl groups in surfactants: Cloisite 20A (C20A) and Cloisite 30B (C30B), respectively. Intercalated and partially delaminated morphologies were corroborated via X-ray diffraction (XRD) and transmission electron microscopy (TEM). Dynamic mechanical analysis (DMA) revealed that PPC-MA was evidently reinforced by the partially delaminated C30B platelets. From XRD patterns of statically annealed PPC-MA/C20A and PPC-MA/C30B mixtures and Fourier transform infrared (FTIR) results of equivalent nanocomposites, partial delamination of C30B in PPC-MA was confirmed to be relevant to diffusion of PPC-MA molecular chains in C30B galleries, grafting of PPC-MA to C30B platelet surfaces and further separation of C30B platelets.

A series of novel AB3-type monomers were prepared from nontoxic natural gallic acid and amino acids. These monomers were then melt-polycondensed in the presence of MgO as a catalyst via a transesterification process at 170-190 degrees C to yield the hyperbranched poly(ester-amide)s bearing terminal acetyl groups. FTIR and NMR spectra confirmed the structures of all the monomers and polymers. The degrees of branching, estimated from 1H NMR and quantitative 13C NMR spectra, were 0.50-0.68. These hyperbranched polymers displayed moderately high molecular weights. Hydrolytic and enzymatic degradation studies were carried out in vitro at 37.5 degrees C in NaOH hydrotropic solution and in Tris-HCl buffer (pH = 8.6) containing proteinase K, respectively. The results indicate that the hyperbranched poly(ester-amide)s are degradable hydrolytically as well as enzymatically, and the rate of hydrolytic degradation increases with the pH value of the solution.

Wide-angle X-ray diffraction (WAXD) was used to investigate the crystal transition of nylon-12,12 under annealing and drawing. The triclinic α-form could be obtained by crystallizing from a melted state or by annealing the γ-form at high temperature (above 150°C). The crystal structure of the α-form annealed at 90 °C didn't change with time except for the perfection of crystals and an increase in the degree of crystallinity. The pseudo-hexagonal γ-form could be produced by crystallizing from the melted state at low temperature (90 °C) or by drawing at 90 and 160 °C. This is the first time a Brill transition has been observed under drawing conditions, instead of under the traditional conditions of continuous heating and cooling. Experimental results also confirm that drawing inducement is preferable to produce the γ-form and plays an important role in determining the crystal structure; there is a competition between drawing inducement and thermal inducement.

The isothermal and nonisothermal crystallization kinetics of partially melted nylon-1212 was investigated with differential scanning calorimetry. Because of partial melting, the pre-existing crystals changed the crystallization mechanism and had a strong effect on the crystallization process. The Avrami exponent and interfacial free energy of the chain-folded surface of partially melted nylon-1212 were higher than those of completely melted nylon-1212. The work of chain folding was determined to be 5.9 kcal/mol. The activation energy of the isothermal crystallization process was determined to be 399.1 kJ/mol, far higher than that of complete melting. The crystallization rate coefficient and Jeziorny analysis indicated that the ability of nonisothermal crystallization for partially melted nylon-1212 was enhanced. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 3222–3230, 2005

In this paper, the structures and properties of the neutral and doped blends of poly(3-dodecylthiophene) (P3DDT) with low-density polyethylene (LDPE) were investigated. Wide-angle X-ray diffraction (WAXD), differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), and scanning electron microscopy (SEM) were used to characterize the structures and morphologies of the blends, and conductivity was also measured. It was found that separate crystallizations occur between P3DDT and LDPE. When the amount of P3DDT is small in the blend, it has the effect of a nucleation reagent and has some influence on the crystal structure. After doping, the interaction force between the molecular chains increases, and leads to a more compact packing and a more uniform dispersion in morphology. Through blending, the thermal stability of pure component could be greatly improved, especially when the P3DDT content is 5 wt %. The conductivity measurements indicate that the conductivity increases with the increase of the P3DDT composition and doping time.

Curcumin, a natural and crystalline compound isolated from the plant Curcuma longa with low toxicity in normal cells, has been shown to protect against carcinogenesis and prevent tumor development. However, little is known about antimetastasis effects and mechanism of curcumin in lung cancer. Rac1 is an important small Rho GTPases family protein and has been widely implicated in cytoskeleton rearrangements and cancer cell migration, invasion and metastasis. In this study, we examined the influence of curcumin on in vitro invasiveness of human lung cancer cells and the expressions of Rac1. The results indicate that curcumin at 10 μM slightly reduced the proliferation of 801D lung cancer cells but showed an obvious inhibitory effect on epidermal growth factor or transforming growth factor β1-induced lung cancer cell migration and invasion. Meanwhile, we demonstrated that the suppression of invasiveness correlated with inhibition of Rac1/PAK1 signaling pathways and matrix metalloproteinase (MMP) 2 and 9 protein expression by combining curcumin treatment with the methods of Rac1 gene silence and overexpression in lung cancer cells. Laser confocal microscope also showed that Rac1-regulated actin cytoskeleton rearrangement may be involved in anti-invasion effect of curcumin on lung cancer cell. At last, through xenograft experiments, we confirmed the connection between Rac1 and the growth and metastasis inhibitory effect of curcumin in vivo. In summary, these data demonstrated that low-toxic levels of curcumin could efficiently inhibit migration and invasion of lung cancer cells through inhibition of Rac1/PAK1 signaling pathway and MMP-2 and MMP-9 expression, which provided a novel insight into the molecular mechanism of curcumin against lung cancer.

Several studies have shown that curcumin can induce apoptosis and inhibit growth in human A549 lung adenocarcinoma cells. However, the mechanism is not completely understood yet. The present study was designed to investigate the effects of curcumin on A549 cells to better understand its apoptosis and apoptosis-related factors in vitro. The apoptosis induction, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were examined by confocal fluorescence microscope and flow cytometry. The MAPK protein expression was examined by Western blot analysis. After treatment with curcumin, apoptosis were observed. Curcumin-induced apoptosis was accompanied by an increase of intracellular ROS level and a loss of MMP. In addition, induction of apoptosis was also accompanied by sustained phosphorylation and activation of JNK, p38 and ERK. However, pretreatment with MAPK inhibitors had no effect upon curcumin-induced apoptosis. GSH and NAC, an anti-oxidant agent, blocked the curcumin-induced ROS production, MMP loss and rescued cells from curcumin-induced apoptosis. Our results indicated that curcumin induced apoptosis in A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway and independent of MAPK signaling pathway.

Several studies have shown that curcumin can induce apoptosis and inhibit growth in human A549 lung adenocarcinoma cells. However, the mechanism is not completely understood yet. In the present study, we investigated the in vitro effect of curcumin on cell viability, apoptosis and disorganization of the actin cytoskeleton in A549 cells. Our results showed that curcumin significantly inhibited the viability of A549 cells in a dose- and time-dependent manner by induced apoptosis. The apoptotic process was associated with a disorganization of the architecture of actin microfilaments and a decrease in the levels of F-actin. DMSO-treated control cells exhibited a well-defined F-actin network that was mainly organized into stress fibers. The actin fibers in cells treated with curcumin or the positive control drug cytochalasin B were disorganized, disassembled, or disrupted, however, the disorganization of actin fibers and apoptosis could be prevented by phalloidin, an F-actin stabilizing compound. Thus, these results demonstrated that actin filament disorganization might play a central role in the curcumin-induced apoptosis of A549 cells.