Search

The pitting corrosion of 304 L austenitic stainless steel joints with 308 L austenitic stainless steel as welding sticks was investigated in simulated concrete pore solutions with different chloride ion concentrations by potentiodynamic polarization curves, electrochemical impedance spectroscopy and Mott-Schottky curves. It is found that chloride ions play an important role in the corrosion behavior of the joints. When the chloride ion concentration increases, the corrosion potential, breakdown potential and charge transfer resistance of the joints at three different weld zones, i. e., base metal (BM), weld metal (WM) and heat affected zone (HAZ), in the simulated solutions decrease, but the charge carrier density and the number of pitting sites in the joints increase. In the same simu-lated solution, the weld metal shows a better corrosion resistance, followed by the heat affected zone, and the base metal has the lowest corrosion resistance due to its much lower charge transfer resistance and higher doping content.

Cancer stem cells (CSCs) have been much proposed as potential tumor eradication targets since they possess highly tumorigenic qualities. However, efficient and fast enrichment of CSCs for cancer biology study and drug screening has been challenging. CD44 is a cell surface receptor for hyaluronic acid (HA) and has been reported as an important CSC marker. Here, we show a simple and label-free method for the enrichment of CSCs highly expressing CD44 using enzymatically crosslinked HA hydrogels. HA hydrogels were formed with different crosslink densities to modulate the interaction between the CD44 and HA chains. We show that HA hydrogels with defined crosslink densities isolated cancer cells expressing high CD44 from breast cancer cell lines in a facile, efficient manner. The enriched cells exhibited CSC-like characteristics such as high expression of CSC markers (octamer-binding transcription factor 4 (OCT4) and aldehyde dehydrogenase 1 (ALDH1)), enhanced tumorsphere formation and chemoresistance. The enriched cells also displayed strong tumorigenicity, metastatic potential and poor survival in vivo. The HA hydrogel provides a simple, fast and efficient platform for CSC enrichment and promotes new anticancer strategies that target breast CSCs. There is strong interest in developing isolation methods for cancer stem cells (CSCs), due in growing desire for CSC eradication for promising cancer therapy. Tumor sphere formation and fluorescence-activated cell sorting have been widely used for CSC isolation, while these methods require cultivation for several days and labelling of cell surface proteins, respectively. A simple and label-free method for breast CSC isolation is developed using HA-based hydrogels with tunable crosslink density. The efficient enrichment of breast CSCs is achieved by HA–CD44 specific interaction, which is controlled by hydrogel crosslink density. We believe that the simple approach that isolates cells with CSC-like characteristics would facilitate the anticancer drug development and cancer research. [ABSTRACT FROM AUTHOR]

When designing drug carriers, the drug-to-carrier ratio is an important consideration, because the use of high quantities of carriers can result in toxicity as a consequence of poor metabolism and elimination of the carriers. However, these issues would be of less concern if both the drug and carrier had therapeutic effects. (−)-Epigallocatechin-3-O-gallate (EGCG), a major ingredient of green tea, has been shown, for example, to possess anticancer effects, anti-HIV effects, neuroprotective effects and DNA-protective effects. Here, we show that sequential self-assembly of the EGCG derivative with anticancer proteins leads to the formation of stable micellar nanocomplexes, which have greater anticancer effects in vitro and in vivo than the free protein. The micellar nanocomplex is obtained by complexation of oligomerized EGCG with the anticancer protein Herceptin to form the core, followed by complexation of poly(ethylene glycol)-EGCG to form the shell. When injected into mice, the Herceptin-loaded micellar nanocomplex demonstrates better tumour selectivity and growth reduction, as well as longer blood half-life, than free Herceptin. [ABSTRACT FROM AUTHOR]

Although naturally occurring membrane lytic antimicrobial peptides (AMPs) and their analogs hold enormous promise for antibiotics-resistant infectious disease therapies, significant challenges such as systemic toxicities, long peptide sequences, poor understanding of structure-activity relationships, and the potential for compromising innate host defense immunity have greatly limited their clinical applicability. To improve the clinical potential of AMPs, a facile approach is adopted to design a series of short synthetic β-sheet folding peptide amphiphiles comprised of short recurring (X1Y1X2Y2)n-NH2 sequences, where X1 and X2: hydrophobic residues (Val, Ile, Phe or Trp), Y1 and Y2: cationic residues (Arg or Lys), and n: number of repeat units; with systematic variations to the cationic and hydrophobic residues to obtain optimized AMP sequences bearing minimal resemblance to naturally occurring sequences. The designed β-sheet forming peptides exhibit broad spectrum antimicrobial activities against various clinically relevant microorganisms, including Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida albicans, with excellent selectivities for microbial membranes. Optimal synthetic peptides with n = 2 and n = 3 repeat units, i.e., (IRIK)2-NH2 and (IRVK)3-NH2, efficiently inhibit sessile biofilm bacteria growth leading to biomass reduction. Additionally, sequences with n = 3 repeat units effectively neutralize endotoxins while causing minimal cytotoxicities. Taken together, these findings clearly demonstrate that the rationally designed synthetic β-sheet folding peptides are highly selective, non-cytotoxic at antimicrobial levels and have tremendous potential for use as broad spectrum antimicrobial agents to overcome multidrug resistance in a wide range of localized, systemic, or external therapeutic applications. [ABSTRACT FROM AUTHOR]

To mediate selective gene delivery to hepatocytes via the asialoglycoprotein receptors (ASGP-Rs), we designed and synthesized well-defined and narrowly dispersed galactose- and glucose-functionalized cationic polycarbonate diblock copolymers (designated as Gal-APC and Glu-APC, respectively) using organocatalytic ring-opening polymerization of functionalized carbonate monomers, with a subsequent quaternization step using bis-tertiary amines to confer quaternary and tertiary amines for DNA binding and endosomal buffering, respectively. The sugar-functionalized diblock copolymers effectively bound and condensed DNA to form positively charged nanoparticles (<100 nm in diameter and ≈30 mV zeta-potential) that were stable under high physiological salt conditions. In comparison to the control Glu-APC/DNA complexes, Gal-APC/DNA complexes mediated significantly higher gene expression in ASGP-R positive HepG2 cells with no significant difference observed in ASGP-R negative HeLa cells. The co-incubation of Gal-APC/DNA complexes with a natural ASGP-R ligand effectively led to a decrease in gene expression, hence providing evidence for the ASGP-R mediated endocytosis of the polyplexes. Importantly, the Gal-APC/DNA complexes induced minimal cytotoxicities in HepG2 cells at the N/P ratios tested. Taken together, the galactose-functionalized cationic polycarbonate diblock copolymer has potential for use as a non-viral gene vector for the targeted delivery of therapeutic genes to hepatocytes in the treatment of liver diseases. [ABSTRACT FROM AUTHOR]

Summary: The screening and characterization of cancer stem cells (CSCs) has been challenging due to sample scarcity. We have developed a miniaturized high-content screening (HCS) assay platform to study intra-cellular proteins related to the survival and apoptosis of CSCs with chemotherapeutic treatment. By overcoming critical bottlenecks associated with sample scarcity, we are able to elucidate the drug responses of the side-population (SP) phenotype characteristics of CSCs. This successful miniaturization of HCS assays facilitates the development of cancer drug treatments, and paves the way for nanoliter volume manipulation for cell-based studies and screening. [ABSTRACT FROM AUTHOR]

Although a few nanomedicines have been approved for clinical use in cancer treatment, that recognizes improved patient safety through targeted delivery, their improved efficacy over conventional drugs has remained marginal. One of the typical drawbacks of nanocarriers for cancer therapy is a low drug-loading capacity that leads to insufficient efficacy and requires an increase in dosage and/or frequency of administration, which in turn increases carrier toxicity. In contrast, elevating drug-loading would cause the risk of nanocarrier instability, resulting in low efficacy and off-target toxicity. This intractable drug-to-carrier ratio has imposed constraints on the design and development of nanocarriers. However, if the nanocarrier has intrinsic therapeutic effects, the efficacy would be synergistically augmented with less concern for the drug-to-carrier ratio. Sunitinib-loaded micellar nanocomplex (SU-MNC) was formed using poly(ethylene glycol)-conjugated epigallocatechin-3- O -gallate (PEG-EGCG) as such a carrier. SU-MNC specifically inhibited the vascular endothelial growth factor-induced proliferation of endothelial cells, exhibiting minimal cytotoxicity to normal renal cells. SU-MNC showed enhanced anticancer effects and less toxicity than SU administered orally/intravenously on human renal cell carcinoma-xenografted mice, demonstrating more efficient effects on anti-angiogenesis, apoptosis induction, and proliferation inhibition against tumors. In comparison, a conventional nanocarrier, SU-loaded polymeric micelle (SU-PM) comprised of PEG- b -poly(lactic acid) (PEG-PLA) copolymer, only reduced toxicity with no elevated efficacy, despite comparable drug-loading and tumor-targeting efficiency to SU-MNC. Improved efficacy of SU-MNC was ascribed to the carrier-drug synergies with the high-performance carrier of PEG-EGCG besides tumor-targeted delivery.

Cervical carcinoma is the fourth most common cause of death in woman, caused by human papillomavirus (HPV) infections and arising from the cervix. Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein, has been linked to tumorigenic effects. In the present study, we screened CKAP2 as a new candidate gene which promotes development of cervical carcinoma, in two independent datasets (TCGA and GSE27678). Results showed that CKAP2 expression was significantly up-regulated in cervical cancerous tissues compared with normal counterparts. Gene set enrichment analysis (GSEA) showed that metastasis, cell cycle and FAK pathways were related with elevated CKAP2 expression. Knockdown of CKAP2 expression significantly inhibited cell proliferation, migration and invasion both in HeLa and C-33A cells. And depletion of CKAP2 down-regulated the expression of metastasis and cell cycle related proteins as well as the phosphorylation of ERK2 (p-ERK2), except E-cadherin. In vivo experiment revealed that knockdown of CKAP2 inhibited C-33A cells proliferation. However, FAK inhibitor PF-562271 and ERK2 inhibitor VX-11e treatment significantly inhibited CKAP2 overexpression-induced cell proliferation, migration and invasion in SiHa cells. In conclusion, our study suggests that CKAP2 acts as a functional oncogene in cervical carcinoma development and may exert its function by targeting FAK-ERK2 signaling pathway.

Objective: To study the relationship between nitric oxide within cervical microenvironment and different HPV types as well as the effect of sodium nitroprusside (SNP), a nitric oxide donor, on the proliferation and apoptosis of cervical cancer cell lines., Methods: HPV typing test was assessed from 115 women by using high-risk HPV (HR-HPV) 21 typing test and the release of cervical nitric oxide (NO) was assessed as nitrate, nitrite in cervical fluid. Cervical NO was then compared between women showing different HPV types. Proliferation of Caski and HeLa cervical cells was determined by methyl thiazolyl tetrazolium (MTT) assay, cell apoptosis was detected by flow cytometry after 24 hours treated by different final concentration of SNP (0.125, 0.25, 0.5, 1.0 and 2.0 mmol/L, respectively). The expressions of HPV E6, E7 gene mRNA and p53 protein were detected by SYBR Green I quantitative real-time PCR and western blot., Results: (1) The cervical NO release of women with HR-HPV was higher compared to that in HPV negative women [(47.6±1.4) µmol/L vs (22.8±0.3) µmol/L; P<0.05]; but there was no statistical difference between low-risk HPV (LR-HPV) group [(24.1±1.2) µmol/L] and control group (P>0.05). (2) After 24 hours treated by different final concentration of SNP, the results shown that SNP could inhibited the proliferation and increased apoptosis rate in Caski and HeLa cells, in which the concentration of SNP≥1.0 mmol/L, there were significantly different (P<0.05), while when SNP≥2.0 mmol/L, the proliferation of cells inhibited seriously. Treated by SNP (1.0 mmol/L) 24 hours, the expressions of HPV18 E6, E7 mRNA in HeLa cells were reduced from 27.362±0.191, 22.962±0.053 to 19.181±0.360, 17.571±0.010 and the protein expression of p53 increased from 1.17±0.03 to 0.23±0.05, there were statistically significant differences between adding SNP group and the control group (P<0.05); but there were no statistically significant differences in HPV16 E6, E7 mRNA and that of p53 in Caski cells (P>0.05)., Conclusions: The presence of HR-HPV is associated with an increased release of NO in the human uterine cervix; NO could inhibit the growth and proliferation and enhance the apoptosis of cervical cancer cells, inhibit the expression of HPV18 E6, E7 mRNA in HeLa cells and activate the expression of p53 protein, the mechanism may be due to higher sensitivity of HeLa cells (cervical adenocarcinoma cell) to SNP. The increasing release of NO may play a role in regulating the elimination of HPV in cervical microenvironment, which is a part of mucous membrane immunity.

Objective: To investigate the effects of follicle stimulating hormone (FSH) on the proliferation, apoptosis, migration and invasion of ovarian cancer cells., Methods: Ovarian cancer cells of the lines SKOV-3 and ES-2 were cultured, and treated by FSH of the concentrations of 10, 20, 40, 80, and 160 mU/ml for 48 h or 24 h respectively. The cells without FSH treatment were used as control cells. The proliferative effects of the cells were detected by MTT colorimetry. The apoptosis and cell cycle were examined by flow cytometry. The matrix metalloproteinases-2 (MMP-2) protein levels in the supernatant were determined by zymography. The cytoplasm levels of MMP-2 protein in cells were tested by Western blotting. RT-PCR was used to detect the expression of MMP-2 mRNA in cells. The migration and invasion of the cells were examined., Results: The a values of the SKOV-3 treated with FSH of the concentrations of 10 - 160 mU/ml were all significantly higher than those without FSH treatment (all P < 0.01). The apoptosis rates of the SKOV-3 treated with FSH of the concentrations 10 - 160 mU/ml were (0.94 +/- 0.06)%, (0.71 +/- 0.03)%, (0.22 +/- 0.02)%, (0.32 +/- 0.02)%, and (0.55 +/- 0.05)% respectively, all significantly lower than those without FSH treatment [(1.30 +/- 0.10)%, all P < 0.01]. After treatment with FSH of the concentrations 40 to 160 mU/ml the percentages of the SKOV-3 at the stage G(0)/G(1) gradually decreased and the cells at the stage S gradually increased compared with the control groups (all P < 0.05). The MMP-2 mRNA and protein expression levels of the SKOV-3 increased with the concentration increase of FSH (P < 0.05 or P < 0.01). Boyden chamber invasive assay showed that the numbers of the SKOV-3 that penetrated the basement membrane were (157 +/- 20)/hp (x200), significantly higher than those of the control groups [(27 +/- 9)/hp, P < 0.01]. Scarification test showed that the distance between scratches of the FSH-treated SKOV-3 cells was significantly shorter than that of the control group (P < 0.01). FSH also induced similar results in ES-2 cells., Conclusion: FSH induces the proliferation, migration, and invasion and suppresses the apoptosis of ovarian cancer cells.

The sequential injection of hyaluronic acid-tyramine conjugates and enzymes forms biodegradable hydrogels in vivo by enzyme-induced oxidative coupling, offering high potential as a promising biomaterial for drug delivery and tissue engineering.