Enzymatic Routes for Chiral Amine Synthesis: Protein Engineering and Process Optimization.

Chiral amines are essential motifs in pharmaceuticals, agrochemicals, and specialty chemicals. While traditional chemical routes to chiral amines often lack stereoselectivity and require harsh conditions, biocatalytic methods using engineered enzymes can offer high efficiency and selectivity under sustainable conditions. This review discusses recent advances in protein engineering of transaminases, oxidases, and other enzymes to improve catalytic performance. Strategies such as directed evolution, immobilization, and computational redesign have expanded substrate scope and enhanced efficiency. Furthermore, process optimization guided by techno-economic assessments has been crucial for establishing viable biomanufacturing routes. Combining state-of-the-art enzyme engineering with multifaceted process development will enable scalable, economical enzymatic synthesis of diverse chiral amine targets.

All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.

The Eya family of proteins (consisting of Eyas1-4 in mammals) play vital roles in embryogenesis by regulating processes such as proliferation, migration/invasion, cellular survival and pluripotency/plasticity of epithelial and mesenchymal states. Eya proteins carry out such diverse functions through a unique combination of transcriptional co-factor, Tyr phosphatase, and PP2A/B55α-mediated Ser/Thr phosphatase activities. Since their initial discovery, re-expression of Eyas has been observed in numerous tumor types, where they are known to promote tumor progression through a combination of their transcriptional and enzymatic activities. Eya proteins thus reinstate developmental processes during malignancy and represent a compelling class of therapeutic targets for inhibiting tumor progression.

Sequential Co-Immobilization of Enzymes on Magnetic Nanoparticles for Efficient l-Xylulose Production.

Multi-enzymatic strategies have shown improvement in bioconversion during cofactor regeneration. In this study, purified l-arabinitol 4-dehydrogenase (LAD) and nicotinamide adenine dinucleotide oxidase (Nox) were immobilized via individual, mixed, and sequential co-immobilization approaches on magnetic nanoparticles, and were evaluated to enhance the conversion of l-arabinitol to l-xylulose. Initially, the immobilization of LAD or Nox on the nanoparticles resulted in a maximum immobilization yield and relative activity of 91.4% and 98.8%, respectively. The immobilized enzymes showed better pH and temperature profiles than the corresponding free enzymes. Furthermore, co-immobilization of these enzymes via mixed and sequential methods resulted in high loadings of 114 and 122 mg/g of support, respectively. Sequential co-immobilization of these enzymes proved more beneficial for higher conversion than mixed co-immobilization because of better retaining Nox residual activity. Sequentially co-immobilized enzymes showed a high relative conversion yield with broader pH, temperature, and storage stability profiles than the controls, along with high reusability. To the best of our knowledge, this is the first report on the mixed or sequential co-immobilization of LAD and Nox on magnetic nanoparticles for l-xylulose production. This finding suggests that selecting a sequential co-immobilization strategy is more beneficial than using individual or mixed co-immobilized enzymes on magnetic nanoparticles for enhancing conversion applications.

von Willebrand factor Ristocetin co-factor activity to von Willebrand factor antigen level ratio for diagnosis of acquired von Willebrand syndrome caused by aortic stenosis.

Background: Severe aortic stenosis (AS) causes acquired von Willebrand syndrome by the excessive shear stress-dependent cleavage of high molecular weight multimers of von Willebrand factor (VWF). While the current standard diagnostic method is so-called VWF multimer analysis that is western blotting under nonreducing conditions, it remains unclear whether a ratio of VWF Ristocetin co-factor activity (VWF:RCo) to VWF antigen levels (VWF:Ag) of <0.7, which can be measured with an automated coagulation analyzer in clinical laboratories and is used for the diagnosis of hereditary von Willebrand disease. Objectives: To evaluated whether the VWF:RCo/VWF:Ag is useful for the diagnosis of AS-induced acquired von Willebrand syndrome. Methods: VWF:RCo and VWF:Ag were evaluated with the VWF large multimer index as a reference, which represents the percentage of a patient's VWF high molecular weight multimer ratio to that of standard plasma in the VWF multimer analysis. Results: We analyzed 382 patients with AS having transaortic valve maximal pressure gradients of >30 mmHg, 27 patients with peripheral artery disease, and 46 control patients free of cardiovascular disease with osteoarthritis, diabetes, and so on. We assumed a large multimer index of <80% as loss of VWF large multimers since 59.0% of patients with severe AS had the indices of <80%, while no control patients or patients with peripheral artery disease, except for 2 patients, exhibited the indices of <80%. The VWF:RCo/VWF:Ag ratios, measured using an automated blood coagulation analyzer, were correlated with the indices (rs = 0.470, P < .001). When the ratio of <0.7 was used as a cut-off point, the sensitivity and specificity to VWF large multimer indices of <80% were 0.437 and 0.826, respectively. Conclusion: VWF:RCo/VWF:Ag ratios of <0.7 may indicate loss of VWF large multimers with high specificity, but low sensitivity. VWF:RCo/VWF:Ag ratios in patients with AS having a ratio of <0.7 may be useful for monitoring the loss of VWF large multimers during their clinical courses.

Metagenome-assembled genomes from High Arctic glaciers highlight the vulnerability of glacier-associated microbiota and their activities to habitat loss.

The rapid warming of the Arctic is threatening the demise of its glaciers and their associated ecosystems. Therefore, there is an urgent need to explore and understand the diversity of genomes resident within glacial ecosystems endangered by human-induced climate change. In this study we use genome-resolved metagenomics to explore the taxonomic and functional diversity of different habitats within glacier-occupied catchments. Comparing different habitats within such catchments offers a natural experiment for understanding the effects of changing habitat extent or even loss upon Arctic microbiota. Through binning and annotation of metagenome-assembled genomes (MAGs) we describe the spatial differences in taxon distribution and their implications for glacier-associated biogeochemical cycling. Multiple taxa associated with carbon cycling included organisms with the potential for carbon monoxide oxidation. Meanwhile, nitrogen fixation was mediated by a single taxon, although diverse taxa contribute to other nitrogen conversions. Genes for sulphur oxidation were prevalent within MAGs implying the potential capacity for sulphur cycling. Finally, we focused on cyanobacterial MAGs, and those within cryoconite, a biodiverse microbe-mineral granular aggregate responsible for darkening glacier surfaces. Although the metagenome-assembled genome of Phormidesmis priestleyi, the cyanobacterium responsible for forming Arctic cryoconite was represented with high coverage, evidence for the biosynthesis of multiple vitamins and co-factors was absent from its MAG. Our results indicate the potential for cross-feeding to sustain P. priestleyi within granular cryoconite. Taken together, genome-resolved metagenomics reveals the vulnerability of glacier-associated microbiota to the deletion of glacial habitats through the rapid warming of the Arctic.

Functional evaluation of complement factor I variants by immunoassays and SDS-PAGE.

Factor I (FI) is an essential regulator of the complement system. Together with co-factors, FI degrades C3b, which inhibits further complement activation. Genetic mutations in FI are associated with pathological conditions like age-related macular degeneration and atypical hemolytic uremic syndome. Here, we evaluated eight recombinant FI genetic variants found in patients. We assessed FI's co-factor activity in the presence of two co-factors; Factor H and soluble CR1. Different analytical assays were employed; SDS-PAGE to evaluate the degradation of C3b, ELISA to measure the generation of fluid phase iC3b and the degradation of surface-bound C3b using a novel Luminex bead-based assay. We demonstrate that mutations in the FIMAC and SP domains of FI led to significantly reduced protease activity, whereas the two analyzed mutations in the LDLRA2 domain did not result in any profound changes in FI's function. The different assays employed displayed a strong positive correlation, but differences in the activity of the genetic variants Ile55Phe and Gly261Asp could only be observed by combining different methods and co-factors for evaluating FI activity. In conclusion, our results provide a new perspective regarding available diagnostic tools for assessing the impact of mutations in FI.

Bothrops atrox and Bothrops lanceolatus Venoms In Vitro Investigation: Composition, Procoagulant Effects, Co-Factor Dependency, and Correction Using Antivenoms.

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.

Dissecting transcription of the 8q24-MYC locus in prostate cancer recognizes the equilibration between androgen receptor direct and indirect dual-functions.

BACKGROUND: Androgen receptor (AR) activation and repression dual-functionality only became known recently and still remains intriguing in prostate cancer (PCa). MYC is a prominent oncogene that functionally entangles with AR signaling in PCa. Further exploration of AR regulatory mechanisms on MYC gene transcription bears clinical and translation significance. METHODS: Bioinformatics analysis of PCa cell line and clinical RNA-Seq and ChIP-Seq (chromatin immunoprecipitation-sequencing) datasets to anchor interactions of AR and MYC transcriptional networks. ChIP-qPCR and 3C (chromosome conformation capture) analyses to probe MYC distal regulation by AR binding sites (ABSs). CRISPR/Cas9-mediated genome-editing to specify functions of ABS within the 8q24-MYC locus on androgen-mediated MYC transcription. Global FoxA1 and HoxB13 distribution profiling to advance AR transcriptional mechanisms. RESULTS: Here we recognize AR bi-directional transcription mechanisms by exploiting the prominent 8q24-MYC locus conferring androgen hyper-sensitivity. At ~ 25 Kb downstream of the MYC gene, we identified an undefined ABS, P10. By chromatin analyses, we validated androgen-dependent spatial interaction between P10 and MYC-Promoter (MYC-Pro) and temporal epigenetic repression of these MYC-proximal elements. We next designed a CRISPR/Cas9-mediated double genomic knock-out (KO) strategy to show that P10-KO slightly lessened androgen-elicited MYC transrepression in LNCaP-AR cells. In similar genomic editing assays, androgen-mediated MYC repression became slightly deepened upon KO of P11, an ABS in the PVT1 gene locus highly enriched in AR-binding motifs and peaks. We also investigated multiple ABSs in the established PCAT1 super-enhancer that distally interacts with MYC-Pro for transactivation, with each KO pool consistently shown to relieve androgen-elicited MYC repression. In the end, we systemically assessed androgen effects in the 8q24-MYC locus and along PCa genome to generalize H3K27ac and BRD4 re-distribution from pioneer factors (FoxA1 and HoxB13) to AR sites. CONCLUSION: Together, we reconciled these observations by unifying AR dual-functions that are mechanistically coupled to and equilibrated by co-factor redistribution.

Factors and co-factors influencing clinical manifestations in nsLTPs allergy: between the good and the bad.

Non-specific lipid transfer proteins (nsLTPs) are a family of plant pan-allergens that represent the primary cause of food allergies in the Mediterranean area, characterized by a wide range of clinical manifestations, ranging from the total absence of symptoms up to anaphylaxis. This wide variety of symptoms is related to the intrinsic capacity of nsLTPs to cause an allergic reaction in a specific subject, but also to the presence of co-factors exacerbating (i.e., exercise, NSAIDs, PPIs, alcohol, cannabis, prolonged fasting, menstruation, acute infections, sleep deprivation, chronic urticaria) or protecting from (i.e., co-sensitization to PR10, profilin or polcalcin) severe reactions. In this picture, recognizing some nsLTPs-related peculiarities (i.e., route, type and number of sensitizations, concentration of the allergen, cross-reactions) and eventual co-factors may help the allergist to define the risk profile of the single patient, in order to promote the appropriate management of the allergy from dietary advices up to the prescription of life-saving epinephrine autoinjector.

Chromatin regulator Ahc1p co-regulates nitrogen metabolism via interactions with multiple transcription factors in Saccharomyces cerevisiae.

Chromatin regulation is an important gene expression/regulation system, but little is known about how it affects nitrogen metabolism in Saccharomyces cerevisiae. A previous study demonstrated the regulatory role of the chromatin regulator Ahc1p on multiple key genes of nitrogen metabolism in S. cerevisiae, but the regulatory mechanism remains unknown. In this study, multiple key nitrogen metabolism genes directly regulated by Ahc1p were identified, and the transcription factors interacting with Ahc1p were analyzed. It was ultimately found that Ahc1p may regulate some key nitrogen metabolism genes in two ways. First, Ahc1p acts as a co-factor and is recruited with transcription factors such as Rtg3p or Gcr1p to facilitate transcription complex binding to target gene core promoters and promote transcription initiation. Second, Ahc1p binds at enhancers to promote the transcription of target genes in concert with transcription factors. This study furthers the understanding of the regulatory network of nitrogen metabolism in S. cerevisiae from an epigenetic perspective.

Metabolic engineering and fermentation optimization strategies for producing organic acids of the tricarboxylic acid cycle by microbial cell factories.

The organic acids of the tricarboxylic acid (TCA) pathway are important platform compounds and are widely used in many areas. The high-productivity strains and high-efficient and low-cost fermentation are required to satisfy a huge market size. The high metabolic flux of the TCA pathway endows microorganisms potential to produce high titers of these organic acids. Coupled with metabolic engineering and fermentation optimization, the titer of the organic acids has been significantly improved in recent years. Herein, we discuss and compare the recent advances in synthetic pathway engineering, cofactor engineering, transporter engineering, and fermentation optimization strategies to maximize the biosynthesis of organic acids. Such engineering strategies were mainly based on the TCA pathway and glyoxylate pathway. Furthermore, organic-acid-secretion enhancement and renewable-substrate-based fermentation are often performed to assist the biosynthesis of organic acids. Further strategies are also discussed to construct high-productivity and acid-resistant strains for industrial large-scale production.

Xylose isomerase from Piromyces sp. E2 is a promiscuous enzyme with epimerase activity.

Xylose isomerase catalyzes the isomerization of D-xylose to D-xylulose with promiscuous activity for other saccharides including D-glucose, D-allose, and L-arabinose. The xylose isomerase from the fungus Piromyces sp. E2 (PirE2_XI) is used to engineer xylose usage by the fermenting yeast Saccharomyces cerevisiae, but its biochemical characterization is poorly understood with divergent catalytic parameters reported. We have measured the kinetic parameters of the PirE2_XI and analyzed its thermostability and pH-dependence towards different substrates. The PirE2_XI shows promiscuous activity towards D-xylose, D-glucose, D-ribose and L-arabinose with variable effects depending on different divalent ions and epimerizes D-xylose at C3 to produce D-ribulose in a substrate/product dependent ratio. The enzyme follows Michaelis-Menten kinetics for the substrates used and although KM values for D-xylose are comparable at 30 and 60 °C, the kcat/KM is three-fold greater at 60 °C. The purified PirE2_XI shows maximal activity at 65 °C in the pH range of 6.5-7.5 and is a thermostable enzyme, maintaining full activity over 48 h at 30 °C or 12 h at 60 °C. This is the first report demonstrating epimerase activity of the PirE2_XI and its ability to isomerize D-ribose and L-arabinose, and provides a comprehensive in vitro study of substrate specificity, effect of metal ions and temperature on enzyme activity and these findings advance the knowledge of the mechanism of action of this enzyme.

Identification of HSPA8 as an interacting partner of MAB21L2 and an important factor in eye development.

BACKGROUND: Pathogenic variants in human MAB21L2 result in microphthalmia, anophthalmia, and coloboma. The exact molecular function of MAB21L2 is currently unknown. We conducted a series of yeast two-hybrid (Y2H) experiments to determine protein interactomes of normal human and zebrafish MAB21L2/mab21l2 as well as human disease-associated variant MAB21L2-p.(Arg51Gly) using human adult retina and zebrafish embryo libraries. RESULTS: These screens identified klhl31, tnpo1, TNPO2/tnpo2, KLC2/klc2, and SPTBN1/sptbn1 as co-factors of MAB21L2/mab21l2. Several factors, including hspa8 and hspa5, were found to interact with MAB21L2-p.Arg51Gly but not wild-type MAB21L2/mab21l2 in Y2H screens. Further analyses via 1-by-1 Y2H assays, co-immunoprecipitation, and mass spectrometry revealed that both normal and variant MAB21L2 interact with HSPA5 and HSPA8. In situ hybridization detected co-expression of hspa5 and hspa8 with mab21l2 during eye development in zebrafish. Examination of zebrafish mutant hspa8hi138Tg identified reduced hspa8 expression associated with severe ocular developmental defects, including small eye, coloboma, and anterior segment dysgenesis. To investigate the effects of hspa8 deficiency on the mab21l2Arg51_Phe52del allele, corresponding zebrafish double mutants were generated and found to be more severely affected than single mutant lines. CONCLUSION: This study identifies heat shock proteins as interacting partners of MAB21L2/mab21l2 and suggests a role for this interaction in vertebrate eye development.

Secretory co-factors in next-generation cellular therapies for cancer.

Since chimeric antigen receptor (CAR) T-cell therapies for hematologic malignancies were approved by the U.S. Food and Drug Administration, numerous "next-generation" CAR T cells have been developed to improve their safety, efficacy, and applicability. Although some of these novel therapeutic strategies are promising, it remains difficult to apply these therapies to solid tumors and to control adverse effects, such as cytokine release syndrome and neurotoxicity. CAR T cells are generated using highly scalable genetic engineering techniques. One of the major strategies for producing next-generation CAR T cells involves the integration of useful co-factor(s) into the artificial genetic design of the CAR gene, resulting in next-generation CAR T cells that express both CAR and the co-factor(s). Many soluble co-factors have been reported for CAR T cells and their therapeutic effects and toxicity have been tested by systemic injection; therefore, CAR T cells harnessing secretory co-factors could be close to clinical application. Here, we review the various secretory co-factors that have been reported to improve the therapeutic efficacy of CAR T cells and ameliorate adverse events. In addition, we discuss the different co-factor expression systems that have been used to optimize their beneficial effects. Altogether, we demonstrate that combining CAR T cells with secretory co-factors will lead to next-generation CAR T-cell therapies that can be used against broader types of cancers and might provide advanced tools for more complicated synthetic immunotherapies.

Metabolic engineering of E. coli for ß-alanine production using a multi-biosensor enabled approach.

ß-alanine is an important biomolecule used in nutraceuticals, pharmaceuticals, and chemical synthesis. The relatively eco-friendly bioproduction of ß-alanine has recently attracted more interest than petroleum-based chemical synthesis. In this work, we developed two types of in vivo high-throughput screening platforms, wherein one was utilized to identify a novel target ribonuclease E (encoded by rne) as well as a redox-cofactor balancing module that can enhance de novo ß-alanine biosynthesis from glucose, and the other was employed for screening fermentation conditions. When combining these approaches with rational upstream and downstream module engineering, an engineered E. coli producer was developed that exhibited 3.4- and 6.6-fold improvement in ß-alanine yield (0.85 mol ß-alanine/mole glucose) and specific ß-alanine production (0.74 g/L/OD600), respectively, compared to the parental strain in a minimal medium. Across all of the strains constructed, the best yielding strain exhibited 1.08 mol ß-alanine/mole glucose (equivalent to 81.2% of theoretic yield). The final engineered strain produced 6.98 g/L ß-alanine in a batch-mode bioreactor and 34.8 g/L through a whole-cell catalysis. This approach demonstrates the utility of biosensor-enabled high-throughput screening for the production of ß-alanine.

Heme Interferes With Complement Factor I-Dependent Regulation by Enhancing Alternative Pathway Activation.

Hemolysis, as a result of disease or exposure to biomaterials, is characterized by excess amounts of cell-free heme intravascularly and consumption of the protective heme-scavenger proteins in plasma. The liberation of heme has been linked to the activation of inflammatory systems, including the complement system, through alternative pathway activation. Here, we investigated the impact of heme on the regulatory function of the complement system. Heme dose-dependently inhibited factor I-mediated degradation of soluble and surface-bound C3b, when incubated in plasma or buffer with complement regulatory proteins. Inhibition occurred with factor H and soluble complement receptor 1 as co-factors, and the mechanism was linked to the direct heme-interaction with factor I. The heme-scavenger protein hemopexin was the main contaminant in purified factor I preparations. This led us to identify that hemopexin formed a complex with factor I in normal human plasma. These complexes were significantly reduced during acute vasoocclusive pain crisis in patients with sickle cell disease, but the complexes were normalized at their baseline outpatient clinic visit. Hemopexin exposed a protective function of factor I activity in vitro, but only when it was present before the addition of heme. In conclusion, we present a mechanistic explanation of how heme promotes uncontrolled complement alternative pathway amplification by interfering with the regulatory capacity of factor I. Reduced levels of hemopexin and hemopexin-factor I complexes during an acute hemolytic crisis is a risk factor for heme-mediated factor I inhibition.

Reliance of Host-Encoded Regulators of Retromobility on Ty1 Promoter Activity or Architecture.

The Ty1 retrotransposon family is maintained in a functional but dormant state by its host, Saccharomyces cerevisiae. Several hundred RHF and RTT genes encoding co-factors and restrictors of Ty1 retromobility, respectively, have been identified. Well-characterized examples include MED3 and MED15, encoding subunits of the Mediator transcriptional co-activator complex; control of retromobility by Med3 and Med15 requires the Ty1 promoter in the U3 region of the long terminal repeat. To characterize the U3-dependence of other Ty1 regulators, we screened a library of 188 known rhf and rtt mutants for altered retromobility of Ty1his3AI expressed from the strong, TATA-less TEF1 promoter or the weak, TATA-containing U3 promoter. Two classes of genes, each including both RHFs and RTTs, were identified. The first class comprising 82 genes that regulated Ty1his3AI retromobility independently of U3 is enriched for RHF genes that restrict the G1 phase of the cell cycle and those involved in transcriptional elongation and mRNA catabolism. The second class of 51 genes regulated retromobility of Ty1his3AI driven only from the U3 promoter. Nineteen U3-dependent regulators (U3DRs) also controlled retromobility of Ty1his3AI driven by the weak, TATA-less PSP2 promoter, suggesting reliance on the low activity of U3. Thirty-one U3DRs failed to modulate P PSP2 -Ty1his3AI retromobility, suggesting dependence on the architecture of U3. To further investigate the U3-dependency of Ty1 regulators, we developed a novel fluorescence-based assay to monitor expression of p22-Gag, a restriction factor expressed from the internal Ty1i promoter. Many U3DRs had minimal effects on levels of Ty1 RNA, Ty1i RNA or p22-Gag. These findings uncover a role for the Ty1 promoter in integrating signals from diverse host factors to modulate Ty1 RNA biogenesis or fate.

The Impact of Genital Ulcers on HIV Transmission Has Been Underestimated-A Critical Review.

In the early 1990s, several observational studies determined that genital ulcer disease (GUD), in either the index or the exposed person, facilitates HIV transmission. Several meta-analyses have since presented associated risk ratios (RR) over the baseline per-act transmission probability (PATP) usually in the range of 2-5. Here we review all relevant observational studies and meta-analyses, and show that the estimation of RRs was, in most cases, biased by assuming the presence of GUD at any time during long follow-up periods, while active genital ulcers were present in a small proportion of the time. Only two studies measured the GUD co-factor effect in PATPs focusing on acts in which ulcers were present, and both found much higher RRs (in the range 11-112). We demonstrate that these high RRs can be reconciled with the studies on which currently accepted low RRs were based, if the calculations are restricted to the actual GUD episodes. Our results indicate that the effect of genital ulcers on the PATP of HIV might be much greater than currently accepted. We conclude that the medical community should work on the assumption that HIV risk is very high during active genital ulcers.

Zinc in soil-plant-human system: A data-analysis review.

Zinc (Zn) plays an important role in the physiology and biochemistry of plants due to its established essentiality and toxicity for living beings at certain Zn concentration i.e., deficient or toxic over the optimum range. Being a vital cofactor of important enzymes, Zn participates in plant metabolic processes therefore, alters the biophysicochemical processes mediated by Zn-related enzymes/proteins. Excess Zn can provoke oxidative damage by enhancing the levels of reactive radicals. Hence, it is imperative to monitor Zn levels and associated biophysicochemical roles, essential or toxic, in the soil-plant interactions. This data-analysis review has critically summarized the recent literature of (i) Zn mobility/phytoavailability in soil (ii) molecular understanding of Zn phytouptake, (iii) uptake and distribution in the plants, (iv) essential roles in plants, (v) phyto-deficiency and phytotoxicity, (vi) detoxification processes to scavenge Zn phytotoxicity inside plants, and (vii) associated health hazards. The review especially compares the essential, deficient and toxic roles of Zn in biophysicochemical and detoxification processes inside the plants. To conclude, this review recommends some Zn-related research perspectives. Overall, this review reveals a thorough representation of Zn bio-geo-physicochemical interactions in soil-plant system using recent data.

Protective Role of the Essential Trace Elements in the Obviation of Cadmium Toxicity: Glimpses of Mechanisms.

Cadmium (Cd) is toxic non-essential heavy metal that precipitates adverse health effects in humans and animals. Chelation therapy, the typical treatment for cadmium toxicity, has certain safety and efficacy issues to treat long term cadmium toxicity, in particular. Recent studies have shown that essential trace elements can play important roles in obviating experimental Cd toxicity. This study organizes and reviews the prototypical evidences of the protective effects of essential trace elements against Cd toxicity in animals and attempts to point out the underlying mechanisms. Zinc, selenium, iron, and combinations thereof are reported to be active. The major mechanisms elucidated inter alia are-induction of metallothionein (MT) synthesis and Cd-MT binding (for zinc), modulation of oxidative stress and apoptosis, interference in cadmium absorption and accumulation from body-thereby maintenance of essential metal homeostasis and cytoprotection. Based on the findings, essential trace elements can be recommended for the susceptible population. The application of these trace elements appears beneficial for both the prevention and remediation of long-term Cd toxicity operative via multiple mechanisms with no or minimal adverse effects as compared to the conventional chelation therapy.