The treatment of triple-negative breast cancer (TNBC) remains a major challenge. The present study aimed to throw more light on the role of copper (I)-nicotinate complex (CNC) as an antitumor as well as a proapoptotic agent. In this study, the HCC-1806 cell line was used as a model for TNBC. Cell cycle, apoptosis assay, and programmed cell death protein-1 were investigated by flowcytometry. Besides, the comet assay was performed using a fluorescence microscope. The enzyme-linked immunosorbent assay technique was used for the detection of phospho-Chk1 at ser 317 and caspase-3. Moreover, the gene expression of survivin was identified by real-time polymerase chain reaction.Finally, superoxide dismutase (SOD) was calorimetrically assayed. The viability of HCC-1806 cells treated with CNC was decreased in a dose-dependent manner. The tendency for apoptotic machinery was observed through the increase in the sub G0 peak, the percentage of early and late apoptotic phases, and the elevation in caspase-3 levels associated with a downregulation of the survivin gene expression. The antioxidant property of the complex, reflected by elevated SOD activity, may contribute to mediate the cell death pathways. Low concentrations of CNC were found to favor the apoptotis-mediated mechanism. However, one cannot neglect the abundance of cell necrosis-mediated death of cells via CNC, especially at higher concentrations.

Metal-organic framework (MOF) nano particles are a class of promising porous nano materials for biomedical applications. Owing to its high loading potential and pH-sensitive degradation, most promising of the MOFs is the zeolitic imidazolate crystal framework (ZIF-8), a progressive useful material for small molecule distribution. Doxorubicin (DOX), designated as a classical drug, was jobwise entrapped in ZIF-8 nano particles. ZIF-8 nano particles, as a novel carrier, were used to monitor the release of the anticancer drug DOX and prevent it from dissipating before reaching its goal. ZIF-8 nano particles with encapsulated DOX (DOX@ZIF-8) can be synthesized in a single pot by incorporation of DOX into the reaction mixture. MOFs and the designed drug delivery (DOX@ZIF-8) system were characterized by Fourier transfer infrared, scanning electron microscopy, N 2 sorption isotherm and X-ray diffraction. The impact of MOFs and the engineered drug delivery system on the viability of human breast and liver cancer cell lines was evaluated. The loaded drug was released at pH 5 faster than at pH 7.4. The nano particles of ZIF-8 showed low cytotoxicity, while DOX@ZIF-8 showed high cytotoxicity to HepG-2 and MCF-7 cells compared with free DOX at the equivalent concentration of DOX of >12.5 μg/ml. These findings indicate that DOX@ZIF-8 nano particles are a promising method for the delivery of cancer cells to drugs. Furthermore, ZIF-8, DOX and encapsulated DOX@ZIF-8 compounds were screened for their potential antibacterial activities against pathogenic bacteria compared with standard antibiotics by the agar well diffusion technique. The results demonstrate that the DOX@ZIF-8 exhibits a strong inhibition zone against Gram-negative strains (Escherichia coli) in comparison with the reference drug gentamycin. The docking active site interactions were evaluated to predict the binding between DOX with the receptor of breast cancer 3hb5-oxidoreductase and liver cancer 2h80-lipid binding protein for anticancer activity.

In an attempt to identify biochemical analytes that could enhance the discrimination between the patients with severe liver fibrosis (F3-F4) and mild fibrosis (F1-F2) based on absolute values of biochemical markers, we measured 12 analytes, including procollagen III aminoterminal propeptide (PIIINP), laminin, proline, hydroxylproline, glycine, AST, ALT, alkaline phosphatase, albumin, total bilirubin, total protein, and prothrombin time in 252 individuals with chronic hepatitis C infection (CHC). PIIINP and laminin were determined by radio-immunoassay; the degraded amino acids were determined using high performance liquid chromatography. Statistical analyses were performed by logistic regression, and receiver operating characteristic (ROC) curves. The best linear combination of blood markers was selected by multivariate discriminant analysis (MDA) for construction of the fibrosis discriminant score (FDS). FDS, an index of five markers (PIIINP, laminin, hydroxyproline, prothrombin activity, and AST/ALT) correctly classified 82% of the patients with severe liver fibrosis at a discriminant cut-off score=-0.5 (i.e., less than -0.5 indicated severe liver fibrosis and greater than -0.5 indicated mild liver fibrosis with sensitivity (76%) and specificity (89%). This result was reproduced in a validation study with no significant difference. In conclusion, FDS is useful for identifying severe liver fibrosis in patients with CHC.

No abstract

New V(IV), Mo(VI), and Ru(II) complexes containing the ligand 2,4‐dihydroxyacetophenone‐S‐methyl dithiocarbazate (H2dhasm); [VO(dhasm)(bpy)] (1) (bpy = 2,2′‐bipyridine), [VO(dhasm)(phen)] (2) (phen = 1,10‐phenanthroline), [MoO2(dhasm)(imz)] (3) (imz = imidazole), [MoO2(dhasm)(DMSO)] (4) (DMSO = dimethylsulfoxide), and [Ru(CO)(PPh3)2(dhasm)] (5) have been synthesized. The ligand and its complexes were structurally characterized by elemental analyses, IR, 1H NMR, EPR, ultraviolet (UV)–visible spectroscopies, magnetic susceptibility, and cyclic voltammetry measurements. Single crystal X‐ray crystallography was used to establish the structure detail of (3) and (4) complexes confirming that the ligand coordinate to the metal ion in a bi‐negative tridentate fashion (dhasm2−, ONS‐donor) in a distorted octahedral geometry. The interaction with calf thymus DNA (CT DNA) of all compounds was studied by UV–visible and fluorescence spectroscopies. Both studies confirmed that these compounds bind to CT DNA through intercalation mode. The DNA cleavage activity of the complexes was also studied on plasmid DNA using gel agarose electrophoresis, and the results revealed that only complexes (2) and (5) have superior cleavage activity in the presence of H2O2. The cytotoxic activity (in vitro) of the complexes on three human cancer cell lines; human liver hepatocellular carcinoma (HepG2), breast adenocarcinoma (MCF7), and epitheliod carcinoma (Hela); and a normal human lung fibroblast (WI‐38) was studied using MTT assay. The complexes exhibited a strong cytotoxicity effect compared with their parent ligand. The ruthenium(II) complex (5) showed the most potent growth inhibition of cancer cells. Also, the mechanism of the apoptotic death in HepG2 cells was studied by observing an increased gene expression of caspase‐3, BAX, P53 and decreased Bcl2 gene expression. The complexes were also screened for their antibacterial activity against gram‐positive and gram‐negative bacteria and showed significant activity against both microorganisms.

No abstract

Tumor metastasis involves the dissemination of malignant cells into the basement membrane, and the vascular system contributes to the circulating pool of these markers. In this context, our aim has been focused on the development of a non-invasive score based on degradation of the backbone of glycosaminoglycans of the extracellular matrix; namely hyaluronic acid (HA), for the assessment of metastasis in patients with breast cancer. HA level was determined by enzyme-linked immunosorbent assay; CA 15.3 was determined by microparticle enzyme immunoassay; hyaluronidase, N-acetyl-β-D-glucosaminidase, β-glucuronidase, glucuronic acid, and glucosamine were assayed by standard colorimetric techniques in 217 patients with breast cancer. Statistical analyses were performed by logistic regression and receiver-operating characteristic analysis curves. The multivariate discriminant analysis selects a score based on absolute values of the six biochemical markers: metastatic breast cancer score (MBCS) = [1.04 (Numerical constant) + 0.003 × CA 15.3 (U/l) + 0.001 × HA (ng/ml) + 0.004 × hyaluronidase (mg N-acetyl-β-D-glucosamine/ml/18 h) + 0.001 × N-acetyl-β-D-glucosaminidase (μmol/ml/min) + 0.026 × glucuronic acid (ng/ml) + 0.003 × glucosamine (μg/dl)]. This function correctly classified 87 % of metastatic breast cancer at cut-off value = 0.85 (i.e., great than 0.85 indicates patients with metastatic breast cancer and less than 0.85 indicates patients with non-metastatic breast cancer). MBCS is a novel, non-invasive, and simple score which can be applied to discriminate patients with metastatic breast cancer.

The current data provided distinct evidence about the favourable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation.