Injectable, In Situ Self-cross-linking, Self-healing Poly(l-glutamic acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering.

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of -CHO/-NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the hydrogels were examined. The PLGA/PEG hydrogels cross-linked by dynamic Schiff base linkages exhibited good self-healing ability. Additionally, the PLGA/PEG hydrogels had good biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and could effectively support BMSC proliferation and deposition of glycosaminoglycans and upregulate the expression of cartilage-specific genes. In a rat cartilage defect model, PLGA/PEG hydrogels significantly promoted new cartilage formation. The results suggest the prospect of the PLGA/PEG hydrogels in cartilage tissue engineering.

A mutagenic analysis of NahE, a hydratase-aldolase in the naphthalene degradative pathway.

NahE is a hydratase-aldolase that converts o-substituted trans-benzylidenepyruvates (H, OH, or CO2-) to benzaldehyde, salicylaldehyde, or 2-carboxybenzaldehyde, respectively, and pyruvate. The enzyme is in a bacterial degradative pathway for naphthalene, which is a toxic and persistent environmental contaminant. Sequence, crystallographic, and mutagenic analysis identified the enzyme as a member of the N-acetylneuraminate lyase (NAL) subgroup in the aldolase superfamily. As such, it has a conserved lysine (Lys183) and tyrosine (Tyr155), for Schiff base formation, as well as a GXXGE motif for binding of the pyruvoyl carboxylate group. A crystal structure of the selenomethionine derivative of NahE shows these active site elements along with nearby residues that might be involved in the mechanism and/or specificity. Mutations of five active site amino acids (Thr65, Trp128, Tyr155, Asn157, and Asn281) were constructed and kinetic parameters measured in order to assess the effect(s) on catalysis. The results show that the two Trp128 mutants (Phe and Tyr) have the least effect on catalysis, whereas amino acids with bulky side chains at Thr65 (Val) and Asn281 (Leu) have the greatest effect. Changing Tyr155 to Phe and Asn157 to Ala also hinders catalysis, and the effects fall in between these extremes. These observations are put into a structural context using a crystal structure of the Schiff base of the reaction intermediate. Trapping experiments with substrate, Na(CN)BH3, and wild type enzyme and selected mutants mostly paralleled the kinetic analysis, and identified two salicylaldehyde-modified lysines: the active site lysine (Lys183) and one outside the active site (Lys279). The latter could be responsible for the observed inhibition of NahE by salicylaldehyde. Together, the results provide new insights into the NahE-catalyzed reaction.

Kinetic study on the molecular mechanism of light-driven inward proton transport by schizorhodopsins.

Schizorhodopsins (SzRs) are light-driven inward proton pumping membrane proteins. A H+ is released to the cytoplasmic solvent from the chromophore, retinal Schiff base (RSB), after light absorption, and then another H+ is bound to the RSB at the end of photocyclic reaction. However, the mechanistic detail of H+ transfers in SzR is almost unknown. Here we studied the deuterium isotope effect and the temperature dependence of the reaction rate constants of elementary steps in the photocycles of SzRs. The former indicated that deprotonation and reprotonation of RSB is mainly accomplished by H+ hopping between heavy atoms with similar H+ affinity. Furthermore, the temperature dependence of the rate constants revealed that most of H+ transfer events have a high entropy barrier. In contrast, the activation enthalpy and entropy of extremely thermostable SzR (MsSzR) are significantly higher than other types of SzRs (SzR1 and MtSzR) suggesting that its highly thermostable structure is optimized with at the cost of slower reaction rates at ambient temperatures.

Vitamin A aldehyde-taurine adducts function in photoreceptor cells.

To facilitate the movement of retinoids through the visual cycle and to limit nonspecific chemical reaction, multiple mechanisms are utilized to handle these molecules when not contained within the binding pocket of opsin. Vitamin A aldehyde is sequestered by reversible Schiff base formation with phosphatidylethanolamine (PE) and subsequently undergoes NADPH-dependent reduction. Otherwise inefficient handling of retinaldehyde can lead to the formation of fluorescent di-retinal compounds within the outer segments of photoreceptor cells. These bisretinoid fluorophores initiate photooxidative processes having adverse consequences for retina. Various carrier proteins confer water solubility and maintain the 11-cis-retinoid configuration. Mechanisms for sequestration of retinoid include the formation of a reversible Schiff base between retinaldehyde and taurine (A1-taurine, A1T), the most abundant amino acid in photoreceptor cells. Here we have undertaken to examine the effects of taurine depletion using the transport inhibitors guanidinoethyl sulfonate (GES) and ß-alanine. Oral treatment of BALB/cJ mice with ß-alanine reduced ocular A1T and the mice exhibited significantly lower scotopic and photopic a-wave amplitudes. As a secondary effect of retinal degeneration, A1T was not detected and taurine was significantly reduced in mice carrying a P23H opsin mutation. The thinning of ONL that is indicative of reduced photoreceptor cell viability in albino Abca4-/- mice was more pronounced in ß-alanine treated mice. Treatment of agouti and albino Abca4-/- mice with ß-alanine and GES was associated with reduced bisretinoid measured chromatographically. Consistent with a reduction in carbonyl scavenging activity by taurine, methylglyoxal-adducts were also increased in the presence of ß-alanine. Taken together these findings support the postulate that A1T serves as a reservoir of vitamin A aldehyde, with diminished A1T explaining reduced photoreceptor light-sensitivity, accentuated ONL thinning in Abca4-/- mice and attenuated bisretinoid formation.

Supramolecular Arrangement and DFT analysis of Zinc(II) Schiff Bases: An Insight towards the Influence of Compartmental Ligands on Binding Interaction with Protein.

We report, for the first time, a detailed crystallographic study of the supramolecular arrangement for a set of zinc(II) Schiff base complexes containing the ligand 2,6-bis((E)-((2-(dimethylamino)ethyl)imino)methyl)-4-R-phenol], where R=methyl/tert-butyl/chloro. The supramolecular study acts as a pre-screening tool for selecting the compartmental ligand R of the Schiff base for effective binding with a targeted protein, bovine serum albumin (BSA). The most stable hexagonal arrangement of the complex [Zn-Me] (R=Me) stabilises the ligand with the highest FMO energy gap (ΔE=4.22 eV) and lowest number of conformations during binding with BSA. In contrast, formation of unstable 3D columnar vertebra for [Zn-Cl] (R=Cl) tend to activate the system with lowest FMO gap (3.75 eV) with highest spontaneity factor in molecular docking. Molecular docking analyses reported in terms of 2D LigPlot+ identified site A, a cleft of domains IB, IIIA and IIIB, as the most probable protein binding site of BSA. Arg144, Glu424, Ser428, Ile455 and Lys114 form the most probable interactions irrespective of the type of compartmental ligands R of the Schiff base whereas Arg185, Glu519, His145, Ile522 act as the differentiating residues with ΔG=-7.3 kcal mol-1 .

Pd-Immobilized Schiff Base Double-Layer Macrocycle: Synthesis, Structures, Peroxidase Mimic Activity, and Antibacterial Performance.

Di-, tri-, and tetra-aldehydes have been employed to access new [2 + 2] [2 + 3] and [2 + 4] double-layer Schiff base macrocycles. The [2 + 3] compound has been used for the immobilization of Pd and the resulting composite has been employed as a peroxidase-like mimetic using 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate; the optimum conditions together with the catalytic kinetics of the enzyme-like activity is discussed. Based on the peroxidase-like catalytic activity, the Pd@Schiff base composite was found to exhibit excellent bactericidal activity against both Escherichia coli (Gram-negative bacterium) and Staphylococcus aureus (Gram-positive bacterium) in the presence of relatively low concentrations of H2O2. Furthermore, cytotoxicity measurements illustrate the biosafety of the Pd composite. The above-mentioned findings have the potential to guide the innovation of new Pd-based composites as enzyme mimetics and antibacterial materials.

Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes.

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the Kb values ranged from 1 × 106 to 3.33 × 105 M-1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

A medium-firm drug-candidate library of cryptand-like structures on T7 phage: design and selection of a strong binder for Hsp90.

We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 109 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (KD = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD).

Hypothalamic MC4R regulates glucose homeostasis through adrenaline-mediated control of glucose reabsorption via renal GLUT2 in mice.

AIMS/HYPOTHESIS: Melanocortin 4 receptor (MC4R) mutation is the most common cause of known monogenic obesity in humans. Unexpectedly, humans and rodents with MC4R deficiency do not develop hyperglycaemia despite chronic obesity and insulin resistance. To explain the underlying mechanisms for this phenotype, we determined the role of MC4R in glucose homeostasis in the presence and absence of obesity in mice. METHODS: We used global and hypothalamus-specific MC4R-deficient mice to investigate the brain regions that contribute to glucose homeostasis via MC4R. We performed oral, intraperitoneal and intravenous glucose tolerance tests in MC4R-deficient mice that were either obese or weight-matched to their littermate controls to define the role of MC4R in glucose regulation independently of changes in body weight. To identify the integrative pathways through which MC4R regulates glucose homeostasis, we measured renal and adrenal sympathetic nerve activity. We also evaluated glucose homeostasis in adrenaline (epinephrine)-deficient mice to investigate the role of adrenaline in mediating the effects of MC4R in glucose homeostasis. We employed a graded [13C6]glucose infusion procedure to quantify renal glucose reabsorption in MC4R-deficient mice. Finally, we measured the levels of renal glucose transporters in hypothalamus-specific MC4R-deficient mice and adrenaline-deficient mice using western blotting to ascertain the molecular mechanisms underlying MC4R control of glucose homeostasis. RESULTS: We found that obese and weight-matched MC4R-deficient mice exhibited improved glucose tolerance due to elevated glucosuria, not enhanced beta cell function. Moreover, MC4R deficiency selectively in the paraventricular nucleus of the hypothalamus (PVH) is responsible for reducing the renal threshold for glucose as measured by graded [13C6]glucose infusion technique. The MC4R deficiency suppressed renal sympathetic nerve activity by 50% in addition to decreasing circulating adrenaline and renal GLUT2 levels in mice, which contributed to the elevated glucosuria. We further report that adrenaline-deficient mice recapitulated the increased excretion of glucose in urine observed in the MC4R-deficient mice. Restoration of circulating adrenaline in both the MC4R- and adrenaline-deficient mice reversed their phenotype of improved glucose tolerance and elevated glucosuria, demonstrating the role of adrenaline in mediating the effects of MC4R on glucose reabsorption. CONCLUSIONS/INTERPRETATION: These findings define a previously unrecognised function of hypothalamic MC4R in glucose reabsorption mediated by adrenaline and renal GLUT2. Taken together, our findings indicate that elevated glucosuria due to low sympathetic tone explains why MC4R deficiency does not cause hyperglycaemia despite inducing obesity and insulin resistance. Graphical abstract.

Synthesis, design, and assessment of novel morpholine-derived Mannich bases as multifunctional agents for the potential enzyme inhibitory properties including docking study.

The synthesized Schiff Bases were reacted with formaldehyde and secondary amine such as 2,6-dimethylmorpholine to afford N-Mannich bases through the Mannich reaction. 3-Substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4) were treated with 2,6-dimethylmorpholine in the presence of formaldehyde to synthesize eight new 1-(2,6-dimethylmorpholino-4-yl-methyl)-3-substitued-4-(4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a-h). The structures of the synthesized eight new compounds were characterized using IR, 1H NMR, 13C NMR, and HR-MS spectroscopic methods. Synthesized compounds inhibitory activity determined against the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione S-transferase (GST) enzymes with Ki values in the range 25.23-42.19 µM for AChE, 19.37-34.22 µM for BChE, and 21.84-41.14 µM for GST, respectively. Binding scores of most active inhibitors against AChE, BChE, and GST enzymes were detected as -10.294 kcal/mol, -9.562 kcal/mol, and -7.112 kcal/mol, respectively. The hydroxybenzylidene moiety of the most active inhibitors caused to inhibition of the enzymes through hydrophobic interaction and hydrogen bond.

Pt(II) and Au(III) complexes containing Schiff-base ligands: A promising source for antitumor treatment.

The effective application of cisplatin in the clinic as an antitumor treatment has stimulated widespread interest in inorganic metal drugs. In particular, complexes containing the transition metals platinum and gold have attracted considerable attention due to their antitumor effects. The Pt(II) and Au(III) Schiff-base complexes are potential antitumor agents because of their remarkable biological activities and good stability, lipophilicity, and electroluminescent properties. These complexes act via various antitumor mechanisms that are unlike those of the classic platinum drugs, providing a feasible solution for improving the serious side effects caused by metal chemotherapy. In this review, promising antitumor agents based on Pt(II) and Au(III) complexes containing Schiff-base ligands, and their biological targets, including G-quadruplex DNA and thioredoxin reductase, are comprehensively summarized.

4-Amino-1,2,4-triazole-3-thione-derived Schiff bases as metallo-ß-lactamase inhibitors.

Resistance to ß-lactam antibiotics in Gram-negatives producing metallo-ß-lactamases (MBLs) represents a major medical threat and there is an extremely urgent need to develop clinically useful inhibitors. We previously reported the original binding mode of 5-substituted-4-amino/H-1,2,4-triazole-3-thione compounds in the catalytic site of an MBL. Moreover, we showed that, although moderately potent, they represented a promising basis for the development of broad-spectrum MBL inhibitors. Here, we synthesized and characterized a large number of 4-amino-1,2,4-triazole-3-thione-derived Schiff bases. Compared to the previous series, the presence of an aryl moiety at position 4 afforded an average 10-fold increase in potency. Among 90 synthetic compounds, more than half inhibited at least one of the six tested MBLs (L1, VIM-4, VIM-2, NDM-1, IMP-1, CphA) with Ki values in the µM to sub-µM range. Several were broad-spectrum inhibitors, also inhibiting the most clinically relevant VIM-2 and NDM-1. Active compounds generally contained halogenated, bicyclic aryl or phenolic moieties at position 5, and one substituent among o-benzoic, 2,4-dihydroxyphenyl, p-benzyloxyphenyl or 3-(m-benzoyl)-phenyl at position 4. The crystallographic structure of VIM-2 in complex with an inhibitor showed the expected binding between the triazole-thione moiety and the dinuclear centre and also revealed a network of interactions involving Phe61, Tyr67, Trp87 and the conserved Asn233. Microbiological analysis suggested that the potentiation activity of the compounds was limited by poor outer membrane penetration or efflux. This was supported by the ability of one compound to restore the susceptibility of an NDM-1-producing E. coli clinical strain toward several ß-lactams in the presence only of a sub-inhibitory concentration of colistin, a permeabilizing agent. Finally, some compounds were tested against the structurally similar di-zinc human glyoxalase II and found weaker inhibitors of the latter enzyme, thus showing a promising selectivity towards MBLs.

A novel hydrazide Schiff base self-assembled nanoprobe for selective detection of human serum albumin and its applications in renal disease surveillance.

Human serum albumin (HSA) is considered as a biomarker for the early diagnosis of renal disease, therefore identifying and detecting HSA in biological fluids (especially urine) with an easy method is of great importance. Herein, we report a novel hydrazide Schiff base fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)pyrazine-2-carbohydrazide (NPC), which self-assembled into nanoparticles in aqueous solution. Based on disassembly-induced emission and the site-specific recognition mechanism, the binding of NPC with HSA resulted in a fluorescence "turn-on" response. Probe NPC exhibited superior selectivity and sensitivity toward HSA with a detection limit of 0.59 mg L-1 in PBS and 0.56 mg L-1 in the urine sample. The site-binding mechanism of NPC with HSA was explored by fluorescence quenching study, Job's plot analysis, HSA destruction, site marker displacement and molecular docking. Fluorescence imaging of HSA in MCF-7 cells was achieved by using a non-toxic NPC probe, suggesting that NPC could be applied to visualize the level of HSA in vivo. More importantly, further practical applications of probe NPC in human urine samples were achieved with satisfactory results by using a fluorometer or test paper, which could provide extensive application in clinical diagnosis.

The Role of Glyoxalase in Glycation and Carbonyl Stress Induced Metabolic Disorders.

Glycation refers to the covalent binding of sugar molecules to macromolecules, such as DNA, proteins, and lipids in a non-enzymatic reaction, resulting in the formation of irreversibly bound products known as advanced glycation end products (AGEs). AGEs are synthesized in high amounts both in pathological conditions, such as diabetes and under physiological conditions resulting in aging. The body's anti-glycation defense mechanisms play a critical role in removing glycated products. However, if this defense system fails, AGEs start accumulating, which results in pathological conditions. Studies have been shown that increased accumulation of AGEs acts as key mediators in multiple diseases, such as diabetes, obesity, arthritis, cancer, atherosclerosis, decreased skin elasticity, male erectile dysfunction, pulmonary fibrosis, aging, and Alzheimer's disease. Furthermore, glycation of nucleotides, proteins, and phospholipids by α-oxoaldehyde metabolites, such as glyoxal (GO) and methylglyoxal (MGO), causes potential damage to the genome, proteome, and lipidome. Glyoxalase-1 (GLO-1) acts as a part of the anti-glycation defense system by carrying out detoxification of GO and MGO. It has been demonstrated that GLO-1 protects dicarbonyl modifications of the proteome and lipidome, thereby impeding the cell signaling and affecting age-related diseases. Its relationship with detoxification and anti-glycation defense is well established. Glycation of proteins by MGO and GO results in protein misfolding, thereby affecting their structure and function. These findings provide evidence for the rationale that the functional modulation of the GLO pathway could be used as a potential therapeutic target. In the present review, we summarized the newly emerged literature on the GLO pathway, including enzymes regulating the process. In addition, we described small bioactive molecules with the potential to modulate the GLO pathway, thereby providing a basis for the development of new treatment strategies against age-related complications.

The DNA repair enzyme MUTYH potentiates cytotoxicity of the alkylating agent MNNG by interacting with abasic sites.

Higher expression of the human DNA repair enzyme MUTYH has previously been shown to be strongly associated with reduced survival in a panel of 24 human lymphoblastoid cell lines exposed to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The molecular mechanism of MUTYH-enhanced MNNG cytotoxicity is unclear, because MUTYH has a well-established role in the repair of oxidative DNA lesions. Here, we show in mouse embryonic fibroblasts (MEFs) that this MNNG-dependent phenotype does not involve oxidative DNA damage and occurs independently of both O6-methyl guanine adduct cytotoxicity and MUTYH-dependent glycosylase activity. We found that blocking of abasic (AP) sites abolishes higher survival of Mutyh-deficient (Mutyh-/-) MEFs, but this blockade had no additive cytotoxicity in WT MEFs, suggesting the cytotoxicity is due to MUTYH interactions with MNNG-induced AP sites. We found that recombinant mouse MUTYH tightly binds AP sites opposite all four canonical undamaged bases and stimulated apurinic/apyrimidinic endonuclease 1 (APE1)-mediated DNA incision. Consistent with these observations, we found that stable expression of WT, but not catalytically-inactive MUTYH, enhances MNNG cytotoxicity in Mutyh-/- MEFs and that MUTYH expression enhances MNNG-induced genomic strand breaks. Taken together, these results suggest that MUTYH enhances the rapid accumulation of AP-site intermediates by interacting with APE1, implicating MUTYH as a factor that modulates the delicate process of base-excision repair independently of its glycosylase activity.

Rational Identification of Hsp90 Inhibitors as Anticancer Lead Molecules by Structure Based Drug Designing Approach.

BACKGROUND: Heat shock protein 90 (Hsp90) is an encouraging anticancer target for the development of clinically significant molecules. Schiff bases play a crucial role in anticancer research because of their ease of synthesis and excellent antiproliferative effect against multiple cancer cell lines. Therefore, we started our research work with the discovery of resorcinol/4-chloro resorcinol derived Schiff bases as Hsp90 inhibitors, which resulted in the discovery of a viable anticancer lead molecule. OBJECTIVE: The objective of the study is to discover more promising lead molecules using our previously established drug discovery program, wherein the rational drug design is achieved by molecular docking studies. METHODS: The docking studies were carried out by using Surflex Geom X programme of Sybyl X-1.2 version software. The molecules with good docking scores were synthesized and their structures were confirmed by IR, 1H NMR and mass spectral analysis. Subsequently, the molecules were evaluated for their potential to attenuate Hsp90 ATPase activity by Malachite green assay. The anticancer effect of the molecules was examined on PC3 prostate cancer cell lines by utilizing 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methodology. RESULTS: Schiff bases 11, 12, 20, 23 and 27 exhibiting IC50 value below 1µM and 15µM, in malachite green assay and MTT assay, respectively, emerged as viable lead molecules for future optimization. CONCLUSION: The research work will pave the way for the rational development of cost-effective Schiff bases as Hsp90 inhibitors as the method employed for the synthesis of the molecules is simple, economic and facile.

Understanding the interaction between α-1-acid glycoprotein (AGP) and potential Cu/Zn metallo-drugs of benzimidazole derived organic motifs: A multi-spectroscopic and molecular docking study.

Drug-binding and interactions with plasma proteins strongly affect their efficiency of delivery, hence considered as a key factor in determining the overall pharmacological action. Alpha-1-acid glycoprotein (AGP), a second most abundant plasma protein in blood circulation, has unique drug binding ability and involved in the transportation of various compounds. Here, we have investigated the mechanism of interaction between AGP and potential Cu/Zn metallo-drugs of benzimidazole derived organic motifs (CuL2 and ZnL2, where L is Schiff base ligand) by applying integrated spectroscopic, biophysical techniques and computational molecular docking analyses. We found that both the metallo-drugs (CuL2 and ZnL2) were bound at the central cavity of AGP interacting with the residues of lobe I, lobe II as well as lobe III. The binding of metallo-drugs to AGP occurs in 1:1 M ratios. Hydrogen bonding, electrostatic and hydrophobic interactions played a significant role in stabilizing the AGP-metallo-drug complexes. Binding affinities of both the metallo-drugs towards AGP at 298 K were of the order of 104-105 M-1, corresponding to Gibbs free energy of stabilization of approximately -5.50 to -6.62 kcal mol-1. Furthermore, the spectroscopic investigation by circular dichroism and synchronous fluorescence analyses suggest conformational changes in AGP upon the binding of metallic compounds.

The Use of a Biostimulant Composition to Increase Turkey Viability during the Key Critical Periods of Development.

The paper reports that the treatment of hatching turkey eggs with a mixture composed of colamine, succinic acid, serine, and pyridoxine hydrochloride increased the viability of embryos and reduced incubation wastes. This effect allowed increasing the hatching of turkey poults by 6.73% and the hatchability of eggs, by 4.43%. At the same time, a statistically significant decrease in the key lipid peroxidation products in one-day-old turkey poults was observed. In particular, the content of isolated double bonds decreased 1.47-fold (p < 0.01); diene conjugates, 1.67-fold (p < 0.01); triene conjugates, 1.46-fold (p < 0.05); oxidiene conjugates, 1.48-fold (p < 0.01); and Schiff bases, 1.3-fold compared to the control. All the above-mentioned positively affected survivability in the experimental group, which appeared to be increased by 1% compared to the control.

Assessment of cytotoxic and genotoxic potentials of a mononuclear Fe(II) Schiff base complex with photocatalytic activity in Trigonella.

BACKGROUND: In recent times, coordination complexes of iron in various oxidation states along with variety of ligand systems have been designed and developed for effective treatment of cancer cells without adversely affecting the normal cell and tissues of various organs. METHODS: In this study, we have evaluated the mechanism of action of a Fe(II) Schiff base complex in the crop plant Trigonella foenum-graecum L. (Fenugreek) as the screening system by using morphological, cytological, biochemical and molecular approaches. Further functional characterization was performed using MCF-7 cell line and solid tumour model for the assessment of anti-tumour activity of the complex. RESULTS: Our results indicate efficiency of the Fe(II) Schiff base complex in the induction of double strand breaks in DNA. Complex treatment clearly induced cytotoxic and genotoxic damage in Trigonella seedlings. The Fe-complex treatment caused cell cycle arrest via the activation of ATM-ATR kinase mediated DNA damage response pathway with the compromised expression of CDK1, CDK2 and CyclinB1 protein in Trigonella seedlings. In cultured MCF-7 cells, the complex induces cytotoxicity and DNA fragmentation through intracellular ROS generation. Fe-complex treatment inhibited tumour growth in solid tumour model with no additional side effects. CONCLUSION: The growth inhibitory and cytotoxic effects of the complex result from activation of DNA damage response along with oxidative stress and cell cycle arrest. GENERAL SIGNIFICANCE: Overall, our results have provided comprehensive information on the mechanism of action and efficacy of a Fe(II) Schiff base complex in higher eukaryotic genomes and indicated its future implications as potential therapeutic agent.