Novel Cytochrome P450-3A4 Enzymatic Nanobiosensor for Lapatinib (a Breast Cancer Drug) Developed on a Poly(anilino-co-4-aminobenzoic Acid-Green-Synthesised Indium Nanoparticle) Platform.

Breast cancer (BC) is one of the most common types of cancer disease worldwide and it accounts for thousands of deaths annually. Lapatinib is among the preferred drugs for the treatment of breast cancer. Possible drug toxicity effects of lapatinib can be controlled by real-time determination of the appropriate dose for a patient at the point of care. In this study, a novel highly sensitive polymeric nanobiosensor for lapatinib is presented. A composite of poly(anilino-co-4-aminobenzoic acid) co-polymer {poly(ANI-co-4-ABA)} and coffee extract-based green-synthesized indium nanoparticles (InNPs) was used to develop the sensor platform on a screen-printed carbon electrode (SPCE), i.e., SPCE||poly(ANI-co-4-ABA-InNPs). Cytochrome P450-3A4 (CYP3A4) enzyme and polyethylene glycol (PEG) were incorporated on the modified platform to produce the SPCE||poly(ANI-co-4-ABA-InNPs)|CYP3A4|PEG lapatinib nanobiosensor. Experiments for the determination of the electrochemical response characteristics of the nanobiosensor were performed with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The nanobiosensor calibration for 0-100 ng/mL lapatinib was linear and gave limit of detection (LOD) values of 13.21 ng/mL lapatinib and 18.6 ng/mL lapatinib in physiological buffer and human serum, respectively. The LOD values are much lower than the peak plasma concentration (Cmax) of lapatinib (2.43 µg/mL), which is attained 4 h after the administration of a daily dose of 1250 mg lapatinib. The electrochemical nanobiosensor also exhibited excellent anti-interference performance and stability.

Green Synthesis of Iron Oxide (Hematite) Nanoparticles and Their Influence on Sorghum bicolor Growth under Drought Stress.

Drought is a major abiotic stress that confronts plant growth and productivity, thus compromising food security. Plants use physiological and biochemical mechanisms to cope with drought stress, but at the expense of growth. Green-synthesized nanoparticles (NPs) have gained great attention in agriculture due to their environmental friendliness and affordability while serving as potential biofertilizers. This study investigates the role of hematite (αFe2O3) NPs, synthesized from Aspalathus linearis (rooibos), to improve Sorghum bicolor growth under drought stress. About 18 nm, spherical, and highly agglomerated hematite (αFe2O3) NPs were obtained. Sorghum seeds were primed with 5, 10, and 15 mg/L αFe2O3 NPs, and, after seven days of germination, the seedlings were transferred into potting soil, cultivated for fourteen days, and were subsequently water deprived (WD) for a further seven days. A reduction in plant height (78%), fresh (FW; 35%) and dry (DW; 36%) weights, and chlorophyll (chl) content ((total chl (81%), chla (135%), and chlb (1827%)) was observed in WD plants, and this correlated with low nutrients (Mg, Si, P, and K) and alteration in the anatomic structure (epidermis and vascular bundle tissues). Oxidative damage was observed as deep blue (O2●-) and brown (H2O2) spots on the leaves of WD plants, in addition to a 25% and 40% increase in oxidative stress markers (H2O2 and MDA) and osmolytes (proline and total soluble sugars), respectively. Seed priming with 10 mg/L αFe2O3 NPs improved plant height (70%), FW (56%), DW (34%), total Chl (104%), chla (160%) and chlb (1936%), anatomic structure, and nutrient distribution. Priming with 10 mg/L αFe2O3 NPs also protected sorghum plants from drought-induced oxidative damage by reducing ROS formation and osmolytes accumulation and prevented biomolecule degradation. The study concludes that green synthesized hematite NPs positively influenced sorghum growth and prevented oxidative damage of biomolecules by improving nutrient uptake and osmoregulation under drought stress.

Solution structure of RING finger-like domain of retinoblastoma-binding protein-6 (RBBP6) suggests it functions as a U-box.

Retinoblastoma-binding protein-6 (RBBP6) plays a facilitating role, through its RING finger-like domain, in the ubiquitination of p53 by Hdm2 that is suggestive of E4-like activity. Although the presence of eight conserved cysteine residues makes it highly probable that the RING finger-like domain coordinates two zinc ions, analysis of the primary sequence suggests an alternative classification as a member of the U-box family, the members of which do not bind zinc ions. We show here that despite binding two zinc ions, the domain adopts a homodimeric structure highly similar to those of a number of U-boxes. Zinc ions could be replaced by cadmium ions without significantly disrupting the structure or the stability of the domain, although the rate of substitution was an order of magnitude slower than any previous measurement, suggesting that the structure is particularly stable, a conclusion supported by the high thermal stability of the domain. A hallmark of U-box-containing proteins is their association with chaperones, with which they cooperate in eliminating irretrievably unfolded proteins by tagging them for degradation by the proteasome. Using a yeast two-hybrid screen, we show that RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. Taken together with the structural similarities to U-box-containing proteins, our data suggest that RBBP6 plays a role in chaperone-mediated ubiquitination and possibly in protein quality control.