Magnesium (Mg) as a bimetal plays critical roles in biochemical processes, membrane stability, and enzyme activity. Mg transporters (MGTs) are involving in maintaining Mg homeostasis in cells. Although the MGT family members have been identified in different plant species, there is no comprehensive analysis of the other plants' MGT genes. In the current study, 62 and 41 non-redundant putative MGT proteins were recognized into the genome of Camelina sativa, and Triticum turgidum and they were compared based on physicochemical properties, protein structure, expression, and interaction. All identified MGTs were classified into three subgroups, NIPA, CorA, and MRS2/MGT, based on conserved-motifs distribution. The results showed that the secondary structure pattern in NIPA and MRS2 subfamily members in both studied plant species were highly similar. Furthermore, MGTs encompass the conserved structures and the critical sites mainly in the metal ion and Mg2+ binding centers as well as the catalytic sites were observed. The highest numbers of protein channels were predicted in CorA proteins in both C. sativa and T. turgidum with 24 and 17 channel numbers, respectively. The Ser, Pro, Gly, Lys, Tyr, and Arg amino acids were predicted as the binding residues in MGTs channel regions. The expression pattern of identified genes demonstrated that MGT genes have diverse tissue-specific expression and stress response expression patterns. Besides, 147 co-expressed genes with MGTs were clustered into the eight co-expression nodes involved in N-glycan biosynthesis, protein processing in the endoplasmic reticulum, carbon metabolism, biosynthesis of amino acids, and endocytosis. In the present study, all interpretations are based on in silico predictions, which can be used in further studies related to functional genomics of MGT genes.

Sodium metavanadate (NaVO3) exhibits important physiological effects including insulin-like, chemoprevention and anticancer activity. However, the effects of NaVO3 on breast cancer and underlying mechanisms are still unclear. In this study, our results revealed that NaVO3 was able to inhibit proliferation of murine breast cancer cells 4T1 with IC50 value of 8.19μM and 1.92μM at 24h and 48h, respectively. The mechanisms underlying the inhibition activity were that NaVO3 could increase reactive oxygen species (ROS) level in a concentration-dependent way, arrest cells at G2/M phase, diminish the mitochondrial membrane potential (MMP), finally promote the progress of apoptosis. Furthermore, NaVO3 also exhibited a dose-dependent anticancer activity in breast cancer-bearing mice that led to the shrinkage of tumor volume (about 50%), lower microvessel density, less propagating cells and more apoptotic cells in vivo, as compared to the saline group. Therefore, NaVO3 may act as a potential chemotherapeutic agent in breast cancer treatment.

A new schiff base cobalt(III) complex [N,N'-bis(2'-hydroxyphenylacetone)-o-ethanediamine] cobalt(III) (M3) has been synthesized and characterized by single X-ray crystallography. The cytotoxicity of complex M3 was evaluated against HeLa, LoVo, A549, A549/cis cancer cell lines, and the normal cell lines LO2 by MTT assays. The IC50 is in the range of 6.27-22.68μM, which is somewhat lower than cisplatin on the basis of platinum molar concentration. Furthermore, anticancer mechanistic studies showed that the complex M3 inhibited cell proliferation by blocking DNA synthesis and then acted on nuclear division of HeLa cells over time. Moreover, western blot analysis indicated M3 dramatically decreased the target protein c-Myc and KLF5 expression levels, and activated many signaling pathways including ER stress, apoptosis, cell cycle and DNA damage in HeLa. M3 did not affect proteasomal activity.

In the case of Proteus vulgaris infection, the increased occurrence of multidrug-resistance strains has become a critical challenge in the treatment of urinary tract diseases. Therefore, using plant extracts as eco-friendly antibacterial provides an attractive solution to battle bacterial infection. The current study investigates the antibacterial and antihemolytic activity of nine medicinal plant extracts against P. vulgaris. Citrus limon extract at 150µg/ml exhibited the highest antimicrobial action against P. vulgaris (the inhibition zone diameter; 22.7mm). Zinc oxide nanoparticles (ZnO NPs) are synthesized using the plant extracts of C. limon, Allium sativum, Sonchus bulbosus, Allium cepa, and Asparagus racemosus. The antibacterial activity of ZnO NPs synthesized using C. limon extract at 150µg/ml is significantly increased (33.8mm). ZnO NPs synthesized using A. cepa, A. racemosus, and C. limon plant extracts are effectively protective for human red blood cells. The ZnO NPs synthesized using C. limon extract are characterized using UV-Visible spectroscopy, FTIR, XRD, and TEM. FTIR revealed that the plant extracts may serve as reducing and capping agents of ZnO NPs. XRD spectra confirmed the crystallinity of ZnO NPs. TEM image demonstrated the formation of spherical shapes of ZnO NPs with an average size of 37.05nm. SEM of P. vulgaris cells treated with ZnO NPs showed cellular morphological damage compared to the untreated cells. ZnO NPs are synthesized by gamma irradiation as a clean and novel method. This study recommended the promising uses of the biosynthesized ZnO NPs using plant extracts as a natural, unique approach, to control the pathogenicity of P. vulgaris.

Bioresorbable stents (BRS) are investigated and designed to revascularize occluded arteries. The iron-based bioresorbable stent is a promising device in interventional therapies, although it's corrosion and bioresorption rate remain challenging. In this work, we introduced a novel nitrided iron coronary stent (IBS) with enhanced degradation rate compared with pure iron stent. To evaluate the biosafety of this device, a sub-chronic systemic toxicity study was conducted and a stainless steel stent (Supporter™) served as a control. Here, the bioresorbable stent was first evaluated in rat abdominal aortic implantation model. When subjected to exaggerated exposure dose, no clinical signs of toxicity or mortality were observed in either, the IBS group or the control group. Histopathological examinations showed the corrosion particles of iron were encapsulated by fibrocytes and engulfed by macrophages, indicating that the degradation of iron was in the early stage. Our results demonstrated that the nitrided iron stent did not induce systemic toxicity under the experimental conditions.

Zinc is an essential micronutrient that plays an important role as a co-factor to several proteins, including zinc-responsive transcription factors. Trichomonas vaginalis is able to survive in the presence of high zinc concentrations in the male urogenital tract. Several genes in T. vaginalis have been shown to respond to changes in zinc concentrations, however, the zinc-dependent mechanism remains undetermined. Recently, we identified in T. vaginalis the zinc finger protein, TvZNF1, which is an ortholog of the mammal metal transcription factor (MTF1). We searched for several of the zinc-responsive genes in T. vaginalis to determine whether if they contain metal response elements (MRE), cis-acting DNA elements that specifically bind MTF1. Six highly conserved over-represented sequence motifs (TvMREs), which share similarity with other eukaryotic MREs, were identified in the zinc-responsive genes in T. vaginalis. We also demonstrated that some of the TvMREs assemble as divalent complexes either as two closely spaced TvMREs or as two overlapping TvMREs forming a palindromic-like sequence: TGCC(N3)GGCA. Electrophoretic mobility shift assays were used to detect the zinc-dependent binding of TvZNF1 and nuclear proteins from T. vaginalis to this specific palindromic motif. Our results support a novel mechanism used by T. vaginalis for the transcriptional regulation of associated zinc-responsive genes through a MTF1/MRE-like system.

Insect epidermal cells secrete a cuticle that serves as an exoskeleton providing mechanical rigidity to each individual, but also insulation, camouflage or communication within their environment. Cuticle deposition and hardening (sclerotization) and pigment synthesis are parallel processes requiring tyrosinase activity, which depends on an unidentified copper-dependent enzyme component in Drosophila melanogaster. We determined the metallomes of fly strains selected for lighter or darker cuticles in a laboratory evolution experiment, asking whether any specific element changed in abundance in concert with pigment deposition. The results showed a correlation between total iron content and strength of pigmentation, which was further corroborated by ferritin iron quantification. To ask if the observed increase in iron body content along with increased pigment deposition could be generalizable, we crossed yellow and ebony alleles causing light and dark pigmentation, respectively, into similar genetic backgrounds and measured their metallomes. Iron remained unaffected in the various mutants providing no support for a causative link between pigmentation and iron content. In contrast, the combined analysis of both experiments suggested instead a correlation between pigment deposition and total copper body content, possibly due to increased demand for epidermal tyrosinase activity.

The presented review is a summary on the current knowledge about metal induced stress response in plants, focusing on the roles of reactive oxygen species, auxin and nitric oxide in roots. The article focuses mainly on the difference between defence and toxicity symptoms of roots during metal-induced stress. Nowadays, pollution of soils by heavy metals is a rapidly growing issue, which affects agriculture and human health. In order to deal with these problems, we must first understand the basic mechanisms and responses to environmental conditions in plants growing under such conditions. Studies so far show somewhat conflicting data, interpreting the same stress responses as both symptoms of defence and toxicity. Therefore, the aim of this review is to give a report about current knowledge of heavy metal-induced stress research, and also to differentiate between toxicity and defence, and outline the challenges of research, focusing on reactive oxygen and nitrogen species, auxin, and the interplay among them. There are still remaining questions on how reactive oxygen and nitrogen species, as well as auxin, can activate either symptoms of toxicity or defence, and adaptation responses.

Oncolytic viruses rewire the immune system and can lead to long-lasting antitumor defenses against primary and metastatic tumors. However, results from clinical studies have shown heterogeneity in responses suggesting that multiplexed approaches may be necessary to consistently generate positive outcomes in patients. To this end, we explored the combination of oncolytic rhabdovirus VSV∆51 with vanadium(V) dipicolinate derivatives, which have already been explored for their antidiabetic properties in animal models. The combination of vanadium-based dipicolinate compounds with VSV∆51 significantly increased viral replication and cytotoxicity in the human renal cell carcinoma cell line 786-0. The effects of three vanadium(V)-dipicolinate coordination complexes ([VO2dipic]-, [VO2dipic-OH]- and [VO2dipic-Cl]- with -OH or -Cl in the para position) were compared to that of the simple salts using spectroscopy and speciation profiles. Like the vanadate salts and the vanadyl cation, all dioxovanadium(V) dipicolinate complexes tested were found to increase viral infection and cytotoxicity when used in combination with VSV∆51. Viral sensitization is dependent on the vanadium since free dipicolinate ligands exerted no effect on viral infection and viability. The ability of these complexes to interact with interfaces and the stability of the complexes were evaluated under physiological conditions. Results indicate that these complexes undergo hydrolysis in cell culturemedia thereby generating vanadate. The vanadium dipicolinate derivatives in the context of immunovirotherapy shares similarities with previous studies exploring the antidiabetic properties of the compounds. The synergy between vanadium compounds and the oncolytic virus suggests that these compounds may be valuable in the development of novel and effective pharmaco-viral therapies.

Studies with patients, animal models of human disease and hemopexin null mice have shown that the heme-binding protein hemopexin is vital for the protection of a variety of cell types and tissues against heme toxicity. The presence of hemopexin in all biological fluids examined to date indicates wide roles in abrogating heme toxicity in human tissues; and, thus, is clinically relevant. Heme-hemopexin endocytosis leads to coordinated trafficking of heme, iron and copper as heme traffics from endosomes to heme oxygenases (HOs) in the smooth endoplasmic reticulum and to the nucleus. This is safe redox-metal trafficking, without oxidative stress, as iron released from heme catabolism by HOs as well as copper taken up with heme-hemopexin move through the cell. To our knowledge, this coordinated metal trafficking has been described only for the hemopexin system and differs from the cell's response to non-protein bound heme, which can be toxic. We propose that defining how cells respond to heme-hemopexin endocytosis, a natural cytoprotective system, will aid our understanding of how cells adapt as they safely respond to increases in heme, Fe(II) and copper. This is relevant for many genetic hemolytic diseases and conditions, stroke and hemorrhage as well as neurodegeneration. Such analyses will help to define a pattern of events that can be utilized to characterize how dysfunctional redox and transition metal handling is linked to the development of pathology in disease states such as Alzheimer's disease when metal homeostasis is not restored; and potentially provide novel targets and approaches to improve therapies.