Features of Reproductive Biology of Papuan Scorpionfish Scorpaenopsis papuensis (Scorpaenidae)

Journal of Ichthyology - Gonadal structure, oocyte morphology, sperm motility after the activation, and spermatozoa ultrastructure are studied in Papuan scorpionfish Scorpaenopsis papuensis. The...     

Talazoparib nanoparticles for overcoming multidrug resistance in triple-negative breast cancer

Herein, we investigated efflux pumps-mediated talazoparib-resistance in the treatment of triple-negative breast cancer (TNBC). Furthermore, we produced a novel talazoparib-solid lipid nanoparticles (SLNs) and then explored in vitro therapeutic efficacy of talazoparib-SLNs to overcome talazoparib-resistance in TNBC cells. Talazoparib-SLNs formulation was produced and then characterized. Calcein and Rho-123 were used to analyze the functional activity of drug efflux pumps in these cells. Additionally, RT-PCR, western blot and immunofluorescence analysis were used to detect the messenger RNA, and protein expression level, and cellular localization of the multidrug resistance (MDR1), breast cancer resistance protein (BCRP), and MRP1. We found that talazoparib efflux was mediated by BCRP and MRP1 pumps in TNBC cells. Talazoparib-SLNs could significantly enhance therapeutic efficacy of talazoparib. Furthermore, talazoparib-SLNs were more effective in the suppression of MDR1, BCRP, and MRP1 gene and protein expression levels than talazoparib. Consequently, this study suggests that talazoparib-SLNs formulation represents a promising therapeutic carrier to reverse MDR-mediated resistance in TNBC.     

Molecular structure and the role of high‐temperature requirement protein 1 in skeletal disorders and cancers

Human high‐temperature requirement protein 1 (HTRA1) is a member of serine proteases and consists of four well‐defined domains—an IGFBP domain, a Kazal domain, a protease domain and a PDZ domain. HTRA1 is a secretory protein and also present intracellularly and associated with microtubules. HTRA1 regulates a broad range of physiological processes via its proteolytic activity. This review examines the role of HTRA1 in bone biology, osteoarthritis, intervertebral disc (IVD) degeneration and tumorigenesis. HTRA1 mediates diverse pathological processes via a variety of signalling pathways, such as TGF‐β and NF‐κB. The expression of HTRA1 is increased in arthritis and IVD degeneration, suggesting that HTRA1 protein is attributed to cartilage degeneration and disease progression. Emerging evidence also suggests that HTRA1 has a role in tumorigenesis. Further understanding the mechanisms by which HTRA1 displays as an extrinsic and intrinsic regulator in a cell type–specific manner will be important for the development of HTRA1 as a therapeutic target.     

Synthesis,structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro

Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)₂(sac)₂]·H₂O (1), trans-[Pt(2-hmpy)₂(sac)₂]·3H₂O (2), trans-[Pd(2-hepy)₂(sac)₂] (3) and trans-[Pt(2-hepy)₂(sac)₂] (4), have been synthesized and characterized by elemental analysis, UV–vis, IR and NMR. Single crystal X-ray analysis reveals that the metal(II) ions in each complex are coordinated by two sac and two 2-hmpy or 2-hepy ligands with a trans arrangement. Anticancer effects of 1–4 were tested against four different cancer cell lines (A549 and PC3 for lung cancer, C6 for glioblastoma, and Hep3B for liver cancer). Cytotoxicity was first screened by the MTT assay and the results were further confirmed by the ATP assay. The mode of cell death was determined by both histological and biochemical methods. Among the metal complexes, complex 2 resulted in relatively stronger anti-growth effect in a dose-dependent manner (3.13–200 μM), compared to the others, by inducing apoptosis.     

Rapid suppression of multidrug resistance of leukemic cells by oxidative srtess

The effect of a short-time (1 h) oxidative stress on multidrug resistance (MDR) of murine leukemic P388VR cells has been investigated. We studied the production of reactive oxygen species (ROS) in cells depending on the composition of medium and the concentration of cells and hydrogen peroxide, as well as the effect of hydrogen peroxide on MDR of cells. MDR was determined from the transport of calcein acetoxymethyl ester out of the cells and from a change in cell sensitivity to vincristine. The amount of ROS arising in cells was determined using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH₂-DA). It was shown that the rate of ROS formation in cells decreases after the addition of serum to the medium and with an increase of the cell number. By the action of hydrogen peroxide, the amount of ROS increases directly with its concentration. Oxidative stress generated by 30–300 μM hydrogen peroxide decreases the MDR of the cells. The effect of hydrogen peroxide increases with the treatment duration and concentration of hydrogen peroxide. MDR determined by the criterion of the efflux of calcein ester from cells is completely suppressed after 1-h exposure to 300 μM hydrogen peroxide. At a concentration of hydrogen peroxide of 60 μM and treatment duration of 1 h, the sensitivity of P388VR cells to vincristine increases to reach the sensitivity of the wild-type P388 cells. Rapid (about 1 h) suppression of MDR is caused by inhibition of the activity of transport proteins. MDR decrease induced by oxidative stress can be used in therapy of tumors resistant to anticancer drugs.     

Bioaccessibility and other key parameters in assessing oral exposure to PAH-contaminated soils and dust: A critical review

Soil ingestion is an important pathway for human exposure to polycyclic aromatic hydrocarbon (PAH)-contaminated soils and dust for children (via ingesting hand residue) as well as for adults (via occupational exposure). An appropriate selection of exposure parameter values is essential for having an accurate risk assessment. This review addresses key parameters for estimating oral exposure to PAH-contaminated soils/dust, discusses their variability and uncertainty, and provides recommendations for value selection. Bioaccessibility (contaminant fraction solubilized in gastro-intestinal tract, available for entering bloodstream and reaching target organs) and soil ingestion rate are two key parameters for exposure assessment (usually characterized by large variability and/or uncertainty), followed by exposure frequency/duration and body weight.     

Protein A immunosensor for the detection of immunoglobulin G by impedance spectroscopy

A novel highly sensitive electrochemical impedimetric Protein A immunosensor for the determination of immunoglobulin G (IgG) was developed by immobilization of Protein A within a newly synthesized, and characterized polymer, poly(maleicanhydride-alt-decene-1). TiO₂ nanoparticles (10–30 nm) were synthesized, characterized with X-ray diffraction, transmission electron microscopy and Brunauer–Emmett–Teller surface analysis. The electron transfer between IgG and the poly(maleicanhydride-alt-decene-1)-TiO₂-Protein A is quasireversible with a formal potential of 225 mV vs Ag|AgCl. The response of the poly(maleicanhydride-alt-decene-1)-TiO₂-Protein A immunosensor was proportional to IgG concentration with a correlation coefficient of 0.9963. The detection limit and linear range was 0.57 ng mL^?1 and 0.0062–500 μg mL^?1, respectively. Impedance measurments showed that synthesized TiO₂ nanoparticles have better conducting properties compared with commercial degussa P25 TiO₂ nanoparticles. The nonspecific binding of anti-MBP was 10 %. The label-free impedimetric immunosensor provided a simple and sensitive detection method for the specific determination of IgG in human serum.     

Platinum(II) and palladium(II) saccharinato complexes with 2,2′:6′,2″-terpyridine: Synthesis, characterization, crystal structures, photoluminescence and thermal studies

[Pd(sac)(terpy)](sac)·4H₂O (1), [Pt(sac)(terpy)](sac)·5H₂O (2), [PdCl(terpy)](sac)·2H₂O (3) and [PtCl(terpy)](sac)·2H₂O (4) (sac = saccharinate, and terpy = 2,2′:6′,2″-terpyridine) have been synthesized and characterized by elemental analysis, FT-IR, ¹H NMR and ¹³C NMR. In 1 and 2, a tridentate terpy ligand together with an N-coordinated sac ligand form the square-planar geometry around the palladium(II) or platinum(II) ions, while one sac anion remains outside the coordination sphere as a counter-ion. X-ray single crystal studies show that the [M(sac)(terpy)]⁺ ions in 1 and 2 reside in the centers of a hydrogen bonded honeycomb network formed by the uncoordinated sac ions and the lattice water molecules. Complexes 3 and 4 are isostructural and consist of a [M(Cl)(terpy)]⁺ cation, a sac anion and two lattice water molecules. The [M(Cl)(terpy)]⁺ ions interact with each other via M-M and π-π stacking interactions and these π interacted units are assembled to a 2D network by water bridges involving the sac ions and lattice water molecules. Convenient synthetic paths for 1-4 are also presented, and spectral, luminescence and thermal properties were discussed.