Plant adaptive strategies have been shaped during evolutionary development in the constant interaction with a plethora of environmental factors, including the presence of metals/metalloids in the environment. Among adaptive reactions against either the excess of trace elements or toxic doses of non-essential elements, their complexation with molecular endogenous ligands, including phenolics, has received increasing attention. Currently, the complexation of phenolics with metal(loid)s is a topic of intensive studies in different scientific fields. In spite of the numerous studies on their chelating capacity, the systemic analysis of phenolics as plant ligands has not been performed yet. Such a systematizing can be performed based on the modern approach of metallomics as an integral biometal science, which in turn has been differentiated into subgroups according to the nature of the bioligands. In this regard, the present review summarizes phenolics–metal(loid)s’ interactions using the metallomic approach. Experimental results on the chelating activity of representative compounds from different phenolic subgroups in vitro and in vivo are systematized. General properties of phenolic ligands and specific properties of anthocyanins are revealed. The novel concept of metallophenolomics is proposed, as a ligand-oriented subgroup of metallomics, which is an integrated approach to study phenolics–metal(loid)s’ complexations. The research subjects of metallophenolomics are outlined according to the methodology of metallomic studies, including mission-oriented biometal sciences (environmental sciences, food sciences and nutrition, medicine, cosmetology, coloration technologies, chemical sciences, material sciences, solar cell sciences). Metallophenolomics opens new prospects to unite multidisciplinary investigations of phenolic–metal(loid) interactions.
Moroctocog alpha is a human B-domain deleted recombinant factor VIII (BDDrFVIII), which represents a new generation of pure antihemophilic products. We describe here an optimized procedure for polyclonal anti-FVIII-antibody production with the use of BDDrFVIII as an immunogen. The main immunochemical characteristics of the produced antibodies and their potential biomedical applications are also reported. Rabbits were immunized with BDDrFVIII as an emulsion with Freund's adjuvant or with antigen immobilized in polyacrylamide gel (PAAG). Antibody titers in immune sera were assayed by enzyme-linked immunosorbent assay (ELISA). IgG purification was performed by affine chromatography on protein A-sepharose. Immune sera and IgG were tested by immunoblotting with the use of human plasma of healthy donors and people with hemophilia A, platelet lysates, and commercial plasma-derived concentrates as sources of FVIII-related antigens. FVIII-producing human umbilical vein cells were processed for immunocytochemical staining with the use of purified anti-FVIII-antibodies. Immunization of rabbits with PAAG-trapped antigen induced more potent immune response compared to the standard immunization procedure with Freund's adjuvant. The lowest working amount of immune IgG, measured by ELISA, was ~50 ng. Immunoblotting demonstrated that anti-BDDrFVIII antibodies effectively recognize the whole FVIII molecule (320 kDa), as well as different truncated polypeptides thereof, and are suitable for immunocytochemical analysis of FVIII-producing cells. An optimized procedure for the production of polyclonal antibodies against FVIII with the use of PAAG-immobilized BDDrFVIII (moroctocog alpha) was proposed and successfully validated. The produced antibodies are suitable for detecting and measuring FVIII-related antigens and may have various biomedical applications.
Cadmium salts are among the TOP-20 of the most dangerous compounds for animals in terms of toxicity. At the same time, today there is a paradigm shift in the studies of cadmium effects: in contrast to the acute effects of intoxication, more importance and practical relevance is attained by studying the continued chronic exposure to small cadmium doses (Chronic Low Cd Exposure) which can take place in real environmental conditions of industrially polluted regions and already impacts about 10% of the world population. While the early changes in kidneys and marker parameters of the urinary system under the action of cadmium are being studied quite actively, cadmium effects on other organs and systems in the body are insufficiently investigated. The purpose of the study was to analyse the multiple effects of cadmium on liver function, osteogenesis, haematopoiesis, and haemostasis in animals and humans. Protective mechanisms that reduce cadmium accumulation in hepatocytes compared to renal cells, in particular, the role of cellular transporters of biogenic metal ions (Fe2+, Zn2+, Mn2+, Cu2+), are systematized. Results and discussion. Cadmium mostly uses divalent metal transporter 1 and Zrt/Irt-like transporters, such as ZIP8 and ZIP14. Given the role of liver in the chelation and deposition of cadmium in the form of complexes with metallothioneins and glutathione, the significant potential of chelating and antioxidant hepatoprotectants to reduce negative effects is suggested. The role of exogenous chemical chelators and antioxidants in detoxifying cadmium is supported by the studies of other cadmium-binding molecules (glutathione, polyphenols, anthocyanins). Both direct effects of cadmium on the osteogenesis and calcium metabolism, and indirect effects on osteoblasts and osteoclasts are considered. In particular, current data on cadmium role in the development of endemic disease Itai-Itai in Japan is discussed. Notably, cadmium effect in children has a special hazards and long-term consequences. Data on cadmium role in interfering Ca2+ metabolism, particularly its effects on epithelial calcium channels (TRPV5) and Na-phosphate co-transporters (SLC34A1) are summarized. Conclusion. Current data suggest that chronic effects of cadmium in ultra-low concentrations upon the osteogenesis are even more evident than in renal system. A review of current data on cadmium effects upon the hematopoietic system in animal models is presented. The earliest studies found relation between cadmium and haemoglobin decrease, which could be mediated by interfering with intracellular Fe traffic, and effects on erythropoietin synthesis. Cadmium affected haemostasis and increased platelet aggregation. Animal studies suggest that chronic cadmium toxicity leads to hypercoagulation and increases the risks of thrombosis. Based on the summarized data, it is concluded that the investigating cadmium effects on hematopoiesis and hemostasis is a promising area for further studies of chronic low-dose cadmium exposure
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