The first single crystal structure of the homoleptic copper (II) ML2 complex (M=Cu (II), L=curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since HTT protein is involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations, however, at higher concentrations, can exacerbate HD by disrupting the glial-neuronal communication, and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for development of a new generation of disease-modifying therapies in HD.

Synthesis and antitumour activity of a palladium compound, [Bis (quinoline) palladium (II) chloride] (coded as NH1) alone and in combination along with its proposed mechanism of action has been described in the present study. Antitumour activity has been performed in seven different cancer cell lines using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The investigated palladium compound demonstrated superiority over clinical standard cisplatin against drug resistant ovarian cancer cell lines. NH1 also demonstrates 4.4 times greater activity than cisplatin against breast cancer model. Binary sequenced combination study showed that NH1 in combination with curcumin is mostly additive to antagonistic. However, combination of NH1 with 6-shogaol demonstrated synergism depending on dose and sequence. Proteomic study revealed that changes in expression of 14 proteins were significantly associated with anticancer mechanism of NH1. In vivo anticancer activity of NH1 at a dose of 0.75 mg/kg was also evaluated using Erlich Ascites Carcinoma (EAC) cell lines in Swiss-albino mice model. Preliminary toxicity study in Swiss-albino mice proved that NH1 is comparatively less toxic at both of the administered doses, either 2.5 mg/kg or 5 mg/kg. However, cisplatin demonstrated significant toxicity at both of the administered doses. Biochemical investigations also supported that NH1 demonstrated lesser toxicity profile towards liver or kidney compared to clinical standard cisplatin.

This paper, the second in a series of two, describes the experimental results for removing arsenic from the dust collected in the electrostatic precipitators of a fluidized bed roasting oven (RP dust). The RP dust produced is discharged as a toxic waste, although its copper content is close to 20% by weight. This work aims to process the RP dust; until obtained a material with a low concentration of arsenic, which could be recirculated in smelting operations and recover the valuable metals. Based on the successful experience obtained in the first document with FS dust, this work proposes to use the reduction-sulphidation-volatilization processes to carry out the volatilization of arsenic from RP dust. A set of experiments was realized in the roasting different ratios of the mixture of copper concentrate / RP dust, sulfur / RP dust varying temperature and roasting time; to reach an arsenic concentration <0.5% by weight. The RP dust was characterized using different techniques, that confirmed more than 20% by weight of copper and describing its structure as a small particle agglomerate (<5 µm), with a complex sulfoxide morphology. The main results indicated: that for a 75/25 mixture of the copper concentrate / PR dust under 700 ° C, 15 minutes roasting time with air atmosphere, the arsenic volatilization was 96% by weight. Meanwhile, for a 5/95 mixture of sulfur / RP dust, at 650 ° C, the volatilization of arsenic was 67% by weight.

The study of the inherent factors that influence the isolation of one type of metallosupramolecular architecture over another is one of the main objectives in the field of Metallosupramolecular Chemistry. In this work, we report two new neutral copper(II) helicates, [Cu2(L1)2]·4CH3CN and [Cu2(L2)2]·CH3CN, obtained by means of an electrochemical methodology and derived from two Schiff-based strands functionalized with ortho- and para-t-butyl groups on the aromatic surface. These small modifications let us to explore the relationship between the ligand design and the structure of the extended metallosupramolecular architecture. The magnetic properties of the Cu(II) helicates were explored by EPR spectroscopy and DC magnetic susceptibility measurements.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for the efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1 and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7, with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10−5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via sequestration of bio-relevant metal ions (i.e. Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared to that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

The primary objective of this study is to synthesize, elucidate the structural properties, and ex-plore the biological activity of novel metal complexes derived from 6-methyl-2-thiouracil and 6-propyl-2-thiouracil. The paper outlines a synthesis method and assesses the antimicrobial activ-ity of newly formed Cu(II) and Pd(II) complexes with two substituted 2-thiouracil ligands. The structural attributes of these newly developed compounds are thoroughly discussed based on data derived from melting point analysis, MP-AES for Cu and Pd, UV-Vis, IR, ATR, 1H NMR, 13C NMR and Raman spectroscopy. The interpretation of the complex spectra is assisted by the data for 6-methyl-2-thiouracil and 6-propyl-2-thiouracil obtained from 1H-1H COSY, DEPT-135, HMBC and HMQC spectra. In addition, the antimicrobial activity of these complexes and the free ligands are assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts.

The photophysical properties of Cu(II) complexes with 5,10,15,20-meso-tetrakis(phenyl)porphyrin and 5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin were examined by luminescence and femtosecond time-resolved absorbance methods respectively. These studies were supported by DFT and TD-DFT calculations which highlight the important role played by a ligand-to-metal charge-transfer states in directing the system towards either intersystem crossing to the triplet hypersurface or coordinative expansion to a five-coordinate quasi-stable intermediate. The latter processes occurs when the porphyrin is photolyzed in the presence of suitably located Lewis bases. Femtosecond time resolved absorbance measurements on Cu(II)-5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin confirm that the coordinative expansion in water occurs in approximately 700 fs while crossing to the triplet hypersurface takes approximately 140 fs in the same solvent. These processes are mutually exclusive, but both can occur simultaneously depending on the environment of the porphyrin. The ratio of the two processes depends on the relative orientation of the Lewis base with respect to the copper atom at the time of excitation. As a consequence, copper porphyrins such as these, are excellent probes to the environment of the porphyrin, and can be used to identify the location of the porphyrin when interacting with DNA fragments.

The goal of this study is to synthesize, determine the structure, and examine the antimicrobial properties of novel metal complexes of 2,4-dithiouracil and its derivatives. These complexes were obtained by mixing aqueous solutions of the corresponding metal salts with the ligand dissolved in DMSO and aqueous NaOH, using a metal-to-ligand ratio of 1:4:2. The structures of the new compounds were analyzed by melting point determination, microwave plasma atomic emission spectrometry (MP-AES) for Cu and Au, inductively coupled plasma optical emission spectrometry (ICP-OES) for S, ATR, solution and solid-state NMR and Raman spectroscopy. The interpretation of the complex spectra was aided by data for 2,4-dithiouracil obtained from 1H-1H COSY, DEPT-135, HMBC, and HMQC spectra. Additionally, the antimicrobial activity of these complex-es and the free ligands was evaluated against Gram-positive and Gram-negative bacteria, as well as yeasts.

This article is a continuation of our previous research on the catalytic capability of chiral copper complex based on commercially available (S)-2-aminomethylpyrrolidine and 3,5-di-tert-butylsalicylaldehyde with various counter-anions in the asymmetric Henry reaction. Our findings indicate that depending on the type of base used, chiral nitroalcohols with yields up to 97% and ee values up to 78%, as well as β-nitrostyrenes with yields up to 82% can be produced. Additionally, it has been found that the outcome of the reaction and the catalytic properties of copper(II) complexes (S)-Cu1 and (S)-Cu2 are influenced by the structure of the aldehyde used.

In this review, the following information describes the manifestation of sleep deprivation by human beings and its adverse effect on their health. Sleep deprivation has been demonstrated into namely two types known as REM sleep and NREM sleep affecting our health in so a problematic way that it is making our body immune to many diseases leading to lethal problems. Therefore, great research by many scientists has discovered that the turmeric “Curcuma longa” which is been used in every Indian kitchen since ancient times, has shown a remarkable effect on the problem caused by sleep deprivation but due to its poor solubility and low bioavailability drawn it into a great disadvantage. But the help of the study of nanotechnology and the evolution of curcumin into nano–curcumin made the possibility of the remarkable effect by making the curcumin more potent and enhancing its stability. Immunological changes due to sleep deprivation lead to Alzheimer’s disease, glioma, neuropathic pains, and many more. Therefore, this review has been summarized as it is been providing information related to curcumin and its affection for sleep deprivation.

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties putting them on a new path in medicine. Their conformational rigidity that improves proteolytic stability, leads to rapid penetration into tissues via any possible route of administration and elimination, occurring by renal metabolism, is of great importance for people with a history of liver diseases. In addition, each ring can function independently, making them extremely versatile molecules for further optimization. In this paper we compared the potentiometric and spectroscopic properties studied by UV-Vis, MCD, and EPR, of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH). In particular we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts, with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively, and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2).

A series of Cu(II)-thiocyanato complexes derived from sterically hindered N-donors diamines were synthesized and characterized: catena-[Cu(Me₃en)(μ-NCS)(NCS)] (1), catena-[Cu(NEt₂Meen)(μ-NCS)(NCS)] (2), catena-[Cu(N,N,2,2-Me₄pn)(μ-NCS)(NCS)] (3), the dimeric: [Cu₂(N,N′-isp₂en)₂(μ-NCS)₂(NCS)₂] (4) and the monomeric complex [Cu(N,N′-t-Bu₂en)(NCS)₂] (5), where Me₃en = N,N,N′-Trimethylethylenediamine, NEt₂Meen = N,N-diethyl-N′-methylethylenediamine, N,N,2,2-Me₄pn = N,N,2,2-tetramethylpropylenediamine, N,N′-isp₂en = N,N′-diisopropylethylenediamine and N,N′-t-Bu₂en = N,N′-di(tert-butyl)ethylenediamine. The complexes were characterized by elemental microanalyse, IR and UV-Vis spectroscopy and single crystal X-ray crystallography. Density Functional Theory was used to evaluate the role of steric effects in compounds 4 and 5 and how this may affect the adaption of a specific geometry, NCS-bonding mode and the dimensionality of the resulting complex.

Curcumin, as the main active component of Turmeric (Curcuma Longa), has been demonstrated with various bioactivities. However, its potential therapeutic applications are hindered by challenges such as poor solubility and bioavailability, rapid metabolism, and pan-assay interference properties. Recent advancements have aimed to overcome these limitations by developing novel curcumin analogues and modifications. This brief review critically assesses recent studies on synthesising different curcumin analogues, including metal complexes, nano particulates, and other curcumin derivatives, focused on the antioxidant, anti-inflammatory, and anticancer effects of curcumin and its modified analogues. Exploring innovative curcumin derivatives offers promising strategies to address the challenges associated with its bioavailability and efficacy and valuable insights for future research directions.

Curcumin, a hydrophobic bioactive constituent from Curcuma longa, has several health promoting properties including anti-atherosclerotic properties. Further, curcumin has blood glucose- and lipid-lowering properties, prophylactic, and therapeutic effects in other cardiometabolic diseases. Atherosclerosis is an umbrella term for a series of degenerative and hyperplasic lesions such as thickening or sclerosis in large and medium -sized artery walls that decrease vascular-wall elasticity and lumen diameter. The atherosclerotic cerebro-cardiovascular disease has become a major concern to human health in recent years. Considering the notable cardiovascular actions of curcumin, the present review summarizes the current status and future perspective of research on curcumin and its ability to prevent or treat atherosclerosis

The new diprotic ligand 3,5-di-tert-butylsalicylaldehyde 4-ethyl-3-thiosemicarbazone, abbreviated H2(3,5-t-Bu2)-sal4eT, exists as the thio-keto tautomer and adopts the E-configuration with respect to the imine double bond as evidenced by single-crystal X-ray analysis and corroborated by spectroscopic characterisation. Upon treatment with Cu(OAc)2·H2O in the presence of either 2,9-dimethyl-1,10-phenanthroline (2,9-Me2-phen) or 1,10-phenanthroline (phen) as a co-ligand in MeOH, this thiosemicarbazone undergoes conformational transformation (relative donor-atom orientations: syn,anti → syn,syn) concomitantly with tautomerization and double deprotonation to afford the ternary copper(II) complexes [Cu{(3,5-t-Bu2)-sal4eT}(2,9-Me2-phen)] (1) and [Cu2{3,5-t-Bu2)-sal4eT}2(phen)] (2). Crystallographic elucidation has revealed that complex 1 is a centrosymmetric dimer of mononuclear copper(II) complex molecules brought about by intermolecular H-bonding. The coordination geometry at the copper(II) centre is best described as distorted square pyramidal in accord with the trigonality index (τ = 0.14). The co-ligand adopts an axial-equatorial coordination mode; hence there is a disparity between its two Cu–N coordinate bonds arising from weakening of the apical one as a consequence of the tetragonal distortion. The axial X-band ESR spectrum of complex 1 is consistent with retention of this structure in solution. Complex 2 is a centrosymmetric dimer of dinuclear copper(II) complex molecules exhibiting intermolecular H-bonding and π-π-stacking interactions. The two copper(II) centres, which are 4.8067(18) Å apart and bridged by the thio-enolate nitrogen of the quadridentate thiosemicarbazonate ligand, display two different coordination geometries, one distorted square planar (τ4 = 0.082) and the other distorted square pyramidal (τ5 = 0.33). Such dinuclear copper(II) thiosemicarbazone complexes, which are crystallographically characterised, are extremely rare. In vitro, complexes 1 and 2 outperform cisplatin as antiproliferative agents in terms of potency and selectivity towards HeLa and MCF-7 cancer cell lines.

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

Glioblastoma (GBL) is one of the more malignant primary brain tumors, currently treated by a multimodality strategy including surgery, radio- and chemotherapy, mainly consisting of Temozolomide(TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival <2 years. The identification of natural molecules having strong anti-tumor activity, led to combine these compounds with conventional chemotherapeutic agents, developing protocols of integrated anticancer therapies. Curcumin (CUR), Resveratrol (RES), and its glucoside Polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies demonstrated that the combination of these natural products was more cytotoxic than the single compound alone in different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To deepen some mechanistic aspects of these results, we investigated if the pretreatment with a combination of CUR+PLD, can improve TMZ cytotoxicity on GBL cells, by analyzing the effects on cell cycle, viability and morphology, on proteins related to cell proliferation, differentiation, apoptosis or autophagy, and on actin network. Cell viability was assessed by MTT or by the cell counter CytoSmart. CalcuSyn software was used to study the CUR+PLD synergism. Morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western Blot. Flow cytometry was used for cell cycle, autophagic flux, and apoptosis analyses. The results obtained provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating antitumor agents such as TMZ, also in drug-resistant GBL cells, through their abilities to affect survival, differentiation, and tumor invasiveness.

Information taken from David A. Scott’s book “Copper and Bronze in Art” was crucial for research on copper corrosion products in Stuttgart. Examples discussed are the nature and variability of ‘Black Spots’ (aka ‘Brown Fuzzies’); cupric hydroxide by cleaning, patination, and pigment synthesis; the wondrous phenomenon of curly malachite; chalconatronite formed by contact to soda glass; the formation of copper formates by glass-induced metal corrosion; and synthesis and X-ray diffraction of basic copper acetates (‘verdigris’).

Copper, along with gold, was among the first metals that humans employed. Thus, copper pol-lution of the world's water resources is escalating, posing a significant threat to human health and aquatic ecosystems. It is crucial to develop a detection technology that is both low-cost and fea-sible, as well as ultra-selective and sensitive. This study explores the use of the NH2-Xxx-His motif-derived peptide from phage display technology for ultra-selective Cu2+ detection. Various Cu-binding M13 phage clones were isolated, and their affinity and cross-reactivity for different metal ions were determined. A detailed analysis of the amino acid sequence of the unique Cu-binding peptides was employed. For the development of an optical chemosensor, a peptide with an NH2-Xxx-His motif was selected. The dansyl group was incorporated during solid phase peptide synthesis, and fluorescence detection assays were employed. The efficacy of the Cu2+-binding peptide was verified through spectroscopic measurements. In summary, we de-veloped a highly selective and sensitive fluorescent chemosensor for Cu2+ detection based on a peptide sequence from phage display library that carries the N-terminal Xxx-His motif.

Millions of people worldwide are affected by diabetes, a chronic disease that continuously grows due to abnormal glucose concentration levels present in the blood. Monitoring blood glucose concentrations is therefore an essential diabetes indicator to aid in the management of the disease. Enzymatic electrochemical glucose sensors presently account for the bulk of glucose sensors in the market. However, their disadvantages are that they are expensive and are dependent on environmental conditions, hence affecting their performance and sensitivity. To meet the increasing demand, non-enzymatic glucose sensors based on chemically modified electrodes for the direct electrocatalytic oxidation of glucose are a good alternative to the costly enzymatic-based sensors currently on the market, and the research thereof continues to grow. Nanotechnology-based biosensors have been explored for their electronic and mechanical properties, resulting in enhanced biological signalling through the direct oxidation of glucose. Copper oxide and copper sulfide exhibit attractive attributes for sensor application, due to their non-toxic nature, abundance, and their unique properties. Thus, in this review, copper oxide and copper sulfide-based materials, are evaluated based on their chemical structure, morphology, and fast electron mobility as suitable electrode materials for non-enzymatic glucose sensors. The review highlights the present challenges of non-enzymatic glucose sensors that have limited their deployment into the market.

Curcumin has attracted attention for its nontoxic chemopreventive effects; however, the specific pathways underlying its anticancer effects in colon cancer remain unclear. This study investigated the potential interplay between curcumin and integrin β1 in colon cancer. HCT116 and fibroblast cells were treated with curcumin, and cell proliferation was assessed using MTT assay and western blotting. We analyzed integrin β1 expression after curcumin treatment of HCT116 cells using western blotting and confocal microscopy. The roles of talin and rab25 in integrin β1 activation by curcumin were investigated using the same methods. Curcumin treatment significantly decreased the survival of HCT 116 cells but did not significantly affect the survival of fibroblast cells. Moreover, curcumin significantly increased integrin β1 expression in HCT 116 cells, which was primarily mediated by talin. In contrast, rab25 expression remained unchanged after curcumin treatment. Using rab25-specific siRNA knockdown experiments, we confirmed that curcumin increased integrin β1 expression even in the absence of rab25. Confocal microscopy revealed a dose-dependent increase in integrin β1 and talin expression, with consistent spatial distribution patterns in response to curcumin. This study highlights the clinical significance of curcumin as a selective anticancer agent in colon cancer by modulating integrin β1 expression through a talin-mediated pathway rather than through rab25.

Incorporating nanoparticles into plant cultivation has been shown to improve growth parameters and alter the bioactive component compositions of many plant species, including Curcumin longa. The aim of the current study was to investigate the effects of foliar application of zinc oxide na-noparticles on the content of bioactive compounds and their antibacterial activities against poten-tial bacterial pathogens. To this end, C. longa leaves were treated with different doses of ZnO NPs to see how they affected bioactive component composition. The effect of different doses of ZnO NPs on the accumulation of bisdemethoxycurcumin, demethoxycurcumin, and curcumin in etha-nolic extracts of C. longa rhizomes was evaluated using high-performance liquid chromatography (HPLC). When compared to the control treatment, foliar spraying with (5 and 40 mgL-1) ZnO NPs increased bisdemethoxycurcumin, demethoxycurcumin, and curcumin levels by approximately (2.69 and 2.84), (2.61 and 3.22), and (2.90 and 3.45) fold, respectively. It was looked at to see if the ethanolic extracts made from the plantlets might change in terms of their phytochemical makeup and antibacterial properties. Furthermore, the results revealed that C. long-ZnO-NPs displayed antibacterial activity against S. aureus and P. aeruginosa tested bacterium strains, but made little attempt against E. coli. The MIC for P. aeruginosa was 100 g/mL. Time-kill studies also revealed that ZnO-NPs at 4 MIC killed P. aeruginosa, Actinobacteria baumannii, and Bacillus sp. after 2 hours, while S. aureus did not grow when treated with 4xMIC of the extract for 6 hours. The strongest antibacterial activity was seen with extract from plantlets grown without nanoparticles for P. aeruginosa, whereas it was seen with extract from plantlets grown in the presence of 5 mg/L ZnO-NPs for E. coli, S. aureus, and P. aeruginosa. These findings show that ZnO-NPs are a pow-erful enhancer of bioactive compound production in C. longa, a trait that can be used to combat antibiotic resistance in pathogenic bacterial species.

The frequent occurrence of rib fractures in slaughtered lambs results in significant economic loss to producers and processors in South Australia and raises concerns about the welfare of the animals. The prevalence of rib fractures became evident through the Enhanced Abattoir Surveillance (EAS) program introduced in 2007. The present study aimed to investigate the association between rib fracture prevalence in lambs at slaughter and their nutrition and management on the farm of origin. The slaughter of 30,055 lambs from 60 farms was monitored at a South Australian abattoir in November 2016. Rib fracture prevalence was 4% (range 0 - 18% per consignment), with all consignments of more than 240 lambs having at least one with fractured ribs. Traceback investigation on 56 of the 60 farms suggests that rib fractures most probably occur during routine husbandry procedures and, based on soil mineral analysis, are associated with calcium inadequacy. There was substantial variation between lines of lambs from different farms, and factors contributing to the differences included line size, region, and soil characteristics, including available calcium. There is a need to modify sheep husbandry and management practices to improve sheep welfare and reduce the cost of rib fractures to the sheep industry.

Heat pumps are increasingly becoming a key solution in the quest for decarbonization, offering a significant advantage over traditional boilers due to their superior energy efficiency. Not only can heat pumps provide both heating and cooling, but they also achieve thermal efficiencies exceeding 500%, which can seem to defy conventional expectations. The outdoor unit of a heat pump consists of about twenty main components, one of which is a complex network of copper pipes and sheets welded to valves, connectors, and other fittings. This set involves over thirty welded joints, highlighting a significant opportunity for reducing manufacturing time through process optimization. Copper is a critical material extensively used in various applications due to its excellent thermal and electrical conductivity. However, these very properties make welding copper particularly challenging, especially when aiming to automate and streamline industrial processes. Traditionally, connecting copper pipes and fittings is done through brazing, yet, alternative methods such as LASER welding, electron beam welding, resistance welding, friction welding, and ultrasonic welding also exist. This study focuses on the ultrasonic welding of copper, aiming to identify the optimal parameters that maximize the mechanical strength of overlapping joints and ensure effective tube sealing. Experimental results showed that for copper sheets, the best outcomes were achieved with a welding time of 3 s and a pressure of 6 bar. For tube sealing, the optimal conditions were a welding time of 3 s and a pressure of 4 bar. For both scenarios, the same variables were used, retention time of 0.62 s, initial pressure of 2 bar, retention pressure of 2 bar and sonotrode rising pressure of 3 bar. The analysis reveals that ultrasonic welding of copper can achieve both robust mechanical strength and reliable sealing, making it a promising technique for industrial applications.

Type 2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders, with a major involvement of oxidative stress in its onset and progression. Pioglitazone (Pio) is an antidiabetic drug which primarily works by reducing insulin resistance while Curcumin (Cur) is powerful antioxidant with o important hypoglycemic effect, also. The both drugs are associated with several drawbacks, such as reduced bioavailability, a short half-life time (Pio) as well as instability and poor water solubility (Cur), which limit their therapeutic use. In order to overcome these disadvantages, a new co-delivery (Pio, Cur) nanosystem based chitosan (CS) (CS-Pio-Cur NPs), was developed, and characterized in reference with simple nanosystems (CS-Pio NPs, CS-Cur NPs). The developed CS-based NPs (CS-Pio-Cur NPs, CS-Pio NPs, CS-Cur NPs) were physico-chemical characterized in terms of particle size (PS), entrapment efficiency (EF%) and loading capacity (LC%). The CS-Pio-Cur NPs proved increased or similar values of EE (88.95% ± 7.79 for Cur; 94.83% ± 9.89 for Pio) and LC% (24.25 % ± 1.62 for Cur; 3.5% ± 0.98 for Pio), in reference with simple nanosystems, CS-Cur NPs (EE = 82.46% ± 1.74; LC = 20.34% ± 0.94) and CS-Pio NPs) (EE = 96.31% ± 0.68; LC = 4.11% ± 0.47), respectively. The identification of APIs (Cur, Pio) loaded into CS matrix was performed using FR-IR spectroscopy and for simultaneously quantification of APIs (Cur, Pio) released from CS-Pio-Cur NPs, a HLPC method was developed and validated. Based on release study performed in different simulated fluids (SGF, SIF, SCF) it can be appreciated that developed CS-APIs NPs have favorable pharmacokinetic profile with good release in gastrointestinal tract.

This study explores the cocrystallization between the drug praziquantel (PZQ) and the nutraceutical curcumin (CU). The investigation revealed two novel solid forms: a cocrystal solvate with ethyl acetate and a non-solvated cocrystal. This novel drug-nutraceutical cocrystal is identi-fied as “generally recognized as safe” (GRAS) praziquantel-curcumin-ethyl acetate (2:1:1) co-crystal solvate. This latter undergoes desolvation, leading to the formation of the praziquan-tel-curcumin (2:1) cocrystal. The cocrystal solvate has ethyl acetate molecules occupying the voids with minimal interactions within the crystal lattice. The application of heat treatment induces solvent removal and prompts the transition to the non-solvated cocrystal, as highlighted by VT-XRD. Thermal analyses demonstrate the stability of the cocrystal solvate up to approximately 100°C, beyond which it transforms into the non-solvated phase, which eventually melts at 130°C.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP) as cross-linking agents. The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied. All formulations showed excellent CUR trapping efficiency, exceeding 90%. In particular, the TPP-crosslinked macrobeads released 34 wt% of the charged CUR within minutes, while the remaining 66 wt% was released slowly due to the biodegradation of CS. The results indicate that the correct choice of gelling agent and its concentration leads to spherical particles capable of encapsulating CUR and releasing it in a wide range of kinetics depending on the specific application.

Curcumin (CUR) is a phytochemical with potent anticancer activities as demonstrated by both preclinical and clinical studies. CUR bioformulations, including loading in biodegradable polymers, have been explored to increase CUR’s solubility and chemical stability, control its release, and improve its delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their curcumin delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. Our characterization indicated that the microsphere copolymers were synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-curcumin showed a significant increase in cell death in MCF-7 cancer cells (IC50 = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Our study integrates in vitro and in silico approaches to identify an optimal co-polymer for the delivery of CUR to cancer cells.

The ameliorative effect ethanolic extract of M. oleifera (MO) leaves in combination of curcumin against seizures, cognitive impairment & oxidative stress PTZ-induced kindled rats. Molecular docking was performed to predict the potential phytochemical of MO and curcumin against Epilepsy. The effect of pretreatment with leaves of M. oleifera ethanolic extracts (MOEE) (250, 500mg/kg, orally), curcumin (200 and 300 mg/kg, orally), valproic acid used as standards (100mg/kg) and combined effect of MOEE (250mg/kg) and curcumin (200mg/kg) at low dose, on pentylenetetrazole (PTZ)-induced kindling. For the development of kindling the individual Wistar rats (Male) were injected pentyletetrazole (40 mg/kg, i.p.) on every alternate day. Molecular Docking has been done by AutoDock4.2 tool to merge the ligand orientations in the binding cavity. From the RCSB website, the crystal structure of Human Glutathione reductase (PDB ID: 3DK9) was obtained. Curcumin and MOEE showed dose-dependent effect. The combined effects of leaves of MOEE & curcumin significantly improved the seizure score and decreased the number of myo-clonic jerks in compare with standard dose of valproic acid. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with MOEE & curcumin. Glutathione reductase (GR) is an enzyme, which plays key role in the cellular control of reactive oxygen species (ROS). Therefore, activating GR can uplift the antioxidant property, which leads to the inhibition of ROS induced cell death in brain. The combination of ethanolic extract of M. oleifera (MOEE) leaves and curcumin have shown better result than any other combination for antiepileptic effect by virtue of antioxidant effects. As per docking study showed that the chloro-genic acid and quercetin is treated with the combination of curcumin can be much more potential.

Wound healing is a process through which skin maintains itself. Once a wound occurs, the inflammatory and proliferative stages are instigated in reaction to injury. It is established that wound restorative comprises four stages including haemostasis, inflammation, proliferation, and remodeling. The amelioration of wound healing is very challenging as tumors can develop at the site of chronic injury. There are numerous plants, plant extracts and plant based natural products were widely used by tribal communities from ancient times for the treatment of cuts, burns, scars, burns and wounds. The therapeutic potential of these plants is recognized due to the presence of phytomolecules such as phenolic compounds, flavonoids, triterpenoids, saponins, tannins, alkaloids and glycosides. The plant used for the treatments of wound healing includes Achillea millefolium, Andrographis paniculata, Boswellia sacra, Calendula officinalis, Crocus sativus, Curcuma longa, Ehretia laevis, Ehretia microphylla, Glycyrrhiza glabra, Malva sylvestris, Rosmarinus officinalis and Salvia officinalis. This assemblage comprises the structures of phytomolecules isolated from the different extracts of these plants, mechanistic insights and important key findings responsible for wound healing. The mechanistic insights involved in wound healing are similar to cytotoxic, anti-inflammatory and antioxidant agents such as ROS generation, DNA fragmentation and western blotting. This review article is an effort to bridge the gaps in the prevailing literature and thus offers gigantic scope for researchers and academicians betrothed in validation of the customary claims and development of safer and efficient and worldwide recognized natural potential candidates as drugs for healing of wounds, burns and cuts.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

Feruloylacetone (FER) is a natural degradant of curcumin after heating, which structurally reserves some functional groups of curcumin. It is not as widely discussed as its original counterpart in previous studies and, therefore, its anti-cancer efficacy is investigated herein. This study focuses on the suppressive effect of FER on colon cancer, as the efficacious effect of curcumin on this typical cancer type has been well evidenced. In addition, demethoxy-feruloylacetone (DFER) was applied to compare the effect that might be brought on by the structural differences of the methoxy group. It was revealed that both FER and DFER inhibited the proliferation of HCT116 cells, possibly via suppression of the phosphorylated mTOR/STAT3 pathway. Notably, FER could significantly repress both the STAT3 phosphorylation and protein levels. Furthermore, both samples showed the capability of arresting HCT116 cells at the G2/M phase via the activation of p53/p21 and upregulation of cyclin-B. In addition, ROS elevation and changes in mitochondrial membrane potential were revealed, as indicated by p-atm elevation. The apoptotic rate rised to 36.9% and 32.2% after being treated by FER and DFER, respectively. In summary, both compounds exhibited an anti-cancer effect, and FER showed a greater pro-apoptotic effect, possibly due to the presence of the methoxy group on the aromatic ring.

Biphasic oily/water nanoemulsions have been proposed as delivery systems for the intranasal administration of curcumin (CUR) and quercetin (QU), due to their high drug entrapment efficiency, the possibility of simultaneous drug administration and protection of the encapsulated compounds from the degradation. To better understand the physicochemical and biological performance of the selected formulation simultaneously co-encapsulating CUR and QU, a stability test of the compounds mixture was firstly carried out using X-ray powder diffraction and thermal analyses, such as differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The determination and quantification of the encapsulated active compounds was then required being an essential tool for the development of innovative nanomedicines. Thus, a new HPLC–UV/Vis method for the simultaneous determination of CUR and QU in the nanoemulsions and their evaluation in stability studies in simulated biological fluids was developed and validated. The X-ray diffraction analyses demonstrated that no interaction between the mixture of active ingredients, if any, is strong enough to take place in the solid state. Moreover, the thermal analysis demonstrated that the CUR and QU are stable in the nanoemulsion production temperature range. The proposed analytical method for the simultaneous quantification of the two actives was selective and linear for both compounds in the range of 0.5 – 12.5 µg/mL (R2 &gt; 0.9997), precise (RSD below 3%), robust and accurate (recovery 100 ± 5 %). The method was validated in accordance with ICH Q2 R1 “Validation of Analytical Procedures” and CDER-FDA 2validation of chromatographic methods” guideline. Furthermore, the low detection (LOD &lt; 0.005 µg/mL for CUR and &lt;0.14 µg/mL for QU) and quantification limits (LOQ &lt; 0.017 µg/mL for CUR and &lt; 0.48 µg/mL for QU) of the method were suitable for the application to drug release and permeation studies planned for the development of the nanoemulsions. The method was then applied for the determination of nanoemulsions CUR and QU encapsulation efficiencies (&gt; 99%), as well as for the stability studies of the two compounds in simulated biological fluids over time. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of CUR, and QU in nanoemulsions.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

Curcumin has restrained clinical applications due to poor bioavailability. This study aimed to synthesize cockle shell-derived calcium carbonate (aragonite) nanoparticles (CSCaCO3NP) for delivery of curcumin and to evaluate its kinetic release in vitro. CSCaCO3NP was synthesized and conjugated with curcumin (Cur-CSCaCO3NP) using a simple top down approach and characterized for its physicochemical properties as a potential curcumin carrier. In vitro release profile was assessed using dialysis bag membrane method. The release data were fitted to Korsmeyer-Peppas, Zero order and Higuchi models to evaluate the mechanism of release pattern. A spherical shaped CSCaCO3NP with a surface area of 14.48±0.1 m2/g, average mean diameter size of 21.38±2.7 nm and a zeta potential of -18.7 mV was synthesized which has a high loading content and encapsulation efficiency. The FT-IR and XRD revealed less observable changes on the peaks after conjugation. In vitro kinetic release profile demonstrated sustained release and best fitted to the Higuchi equation model. The results of this study showed the capacity of the synthesized CSCaCO3NP to encapsulate curcumin efficiently with a stable release in vitro. This could give an insight and supportive ideas on the potentials of CSCaCO3NP for curcumin delivery. Therefore, CSCaCO3NP holds future prospects in preclinical framework to enhance curcumin efficacy for oral therapeutic applications.

This research aimed to establish the relationship between carbon-nitrogen nutritional factors and copper sulfate on laccase activity (LA) by Pleurotus ostreatus. Culture media composition was tested to choose the nitrogen source. Yeast extract (YE) was selected as a better nitrogen source than ammonium sulfate. Then, the effect of glucose and YE concentrations on biomass production and LA as response variables was evaluated using central composite experimental designs with and without copper. The results showed that the best culture medium composition was glucose 45 gL-1 and YE 15 gL-1, simultaneously optimizing these two response variables. The fungal transcriptome was obtained in this medium with or without copper, and the differentially expressed genes were found. Main up-regulated transcripts included three laccase genes (lacc2, lacc6, and lacc10) regulated by copper, whereas the principal down-regulated transcripts included a copper transporter (ctr1) and a regulator of nitrogen metabolism (nmr1). These results suggest that Ctr1, which facilitates the entry of copper in the cell, is regulated by nutrient-sufficiency conditions. Once inside, copper induces transcription of laccase genes. This finding could explain why a 10 to 20-fold increase in LA occurs with copper compared to cultures without copper when using the optimal concentration of YE as nitrogen sources.

Computational investigations on the BPE-ligated Cu-catalysed enantioselective addition of enynes to ketones were performed with DFT method. Two BPE-CuMes catalysts, BPE-CuMes and (S,S)-Ph-BPE–CuMes, were employed to probe the reaction mechanism with the emphasis on stereoselectivity. The calculations on the BPE-CuMes system indicate that the actvie metallized enyne intermediate acts as the catalyst for the catalytic cycle. The catalytic cycle involves two steps: 1) the ketone addition to the alkene moiety of the metallized enyne; 2) the metallization of enyne followed by the release of product with the recovery of the active metallized enyne intermediate. The first step accounts for the distribution of the products, and therefore is the stereo-controlling step in chiral systems. In the chiral (S,S)-Ph-BPE–CuMes system, the steric hindrance is vital for the distribution of products and responsible for the stereoselectivity of this reaction. The steric hindrance between the phenyl ring of the two substrates and groups at the chiral centers in the ligand skeleton is identified as the original of the stereoselectivity for the titled reaction.

Considering Cu(tda) chelate is a receptor for adenine and related 6-aminopurines, now we report the synthesis, molecular and crystal structures, thermal stability, spectral properties and DFT calculations on the [Cu(tda)(9heade)(H2O)]•2H2O (1). N7 is found to be the preferred donor atom of 9heade, that can favor the cooperation of a Cu-N7(9heade) bond and an (9heade)N6-H•••O(tda) interligand interaction. But unprecedentedly, the Cu(tda)-9heade molecular recognition in 1 is essentially featured the Cu-N1(9heade), without any N6-H•••O(carboxyl tda) interligand interaction. Nevertheless, being N1 the most basic donor for N9-substituted adenines, this Cu-N1 bond is now assisted by an O2-water mediated interaction (N6-H•••O2 and O2•••Cu weak contact). Also in the crystal packing, the O-H(ol) of 9heade interacts with its own adenine moiety by an O3-water mediated interaction (O(ol)-H•••O3 plus O3-H36•••π(adenine moiety). In turn these water-mediated interactions seems to be responsible to serious alterations on the physical properties of crystalline or grounded samples. Density functional theory calculations were used to evaluate the interactions energetically. Moreover, the quantum theory of atoms-in-molecules (QTAIM) in combination with the noncovalent interaction plot (NCIPlot) were used to analyze the interactions and rationalize the existence and relative importance of hydrogen bonding, chalcogen bonding and π-stacking interactions.

Copper, the highly toxicity micronutrient, plays two essential roles: it is a catalytic and structural cofactor for Cu-dependent enzymes, and it acts as a secondary messenger. In the cells, copper is imported by CTR1, a transmembrane high-affinity copper importer, and DMT1 (divalent metal transporter). In cytosol, enzyme-specific chaperones receive copper from CTR1 C-terminus and deliver it to their apoenzymes. DMT1 cannot be a donor of catalytic copper because it does not have cytosol domain which is required for copper transfer to the Cu-chaperons and following to cuproenzymes. Here we assume that DMT1 can mediate copper way required for regulatory copper pool. To verify this thought, we used CRISPR/Cas9 to generate H1299 cell line with CTR1 or DMT1 single knockout (KO) and CTR1/DMT1 double knockout (DKO). To confirm KOs of the genes qRT-PCR were used. Two independent clones for each gene were selected for further studies. In CTR1-KO cells, expression of the DMT1 gene was significantly increased. In subcellular compartments, copper concentration decreased dramatically in DKO cells. CTR1-KO cells, but not DMT1-KO, demonstrated reduced sensitivity to cisplatin and silver ions, agents that enter the cell through CTR1. The expression of genes, whose protein products require copper: HIF1α, XIAP, COMMD1, CCS, Cp, but not SOD1 and NF-kB, changed their level. Perhaps these data will help to understand how the disturbances of copper homeodynamics lead to the development of neurodegenerative and oncological disorders. Possibility of using CTR1 KO and DMT1 KO cells to study homeodynamics of catalytic and signaling copper selectively is discussed.

Copper (Cu)-based fungicides are widely used in agriculture, but excessive Cu accumulation in soils threatens crop performance, particularly in perennial fruit crops like apples. This study investigated the effects of varying Cu concentrations on the physiological responses of three apple varieties—Braeburn, Fuji, and Cripps Pink—using a callus-media system. Callus cultures were exposed to Cu concentrations ranging from 0 to 20 mg Cu kg⁻¹ to assess traits such as growth, fresh and dry weight, copper accumulation, and bioconcentration factor (BCF). Results revealed that media Cu concentration had a stronger effect than variety on most traits, especially above 10 mg Cu kg⁻¹, where copper stress reduced genetic variability. At lower Cu concentrations, varietal differences were more apparent, with Cripps Pink showing greater copper tolerance. These findings suggest that high Cu levels suppress varietal differences, leading to a uniform stress response. This study provides valuable insights into copper toxicity in apple varieties and highlights the need to maintain soil Cu levels below critical thresholds to preserve varietal performance, with potential implications for soil-plant systems.

In recent years, foodborne biomaterials have been widely used in wound healing, and they have attracted much attention because of their advantages of green, environmental protection and pollution-free. Therefore ，in this study, ginger, a commonly used medicine in traditional Chinese medicine, was used to prepare ginger extract (Ginger E) as wound healing dressing, and its effect was comprehensively compared with curcumin. The results showed that Ginger E and curcumin had excellent biocompatibility and bioactivity. Among them, Ginger E showed better ability to promote cell migration, angiogenesis and intracellular reactive oxygen species (ROS) clearance than curcumin. And Ginger E behaved better anti-inflammatory and antioxidant activity. The results of animal experiments further demonstrate that Ginger E can promote angiogenesis and collagen deposition, promote the expression of anti-inflammatory factors, and refrain from the expression of pro-inflammatory factors, thus showing great potential in wound healing.

Treatment with herbal medicine continues to enjoy widespread popularity not only in the developing world, because of low costs, easy availability, and low risk of adverse effects. One such plant is Curcumin longa L., or turmeric, which has a long history of both culinary and medicinal uses throughout Asia, spanning thousands of years. In addition to traditionally being used as a dye, as a flavouring and colouring agent in foods, and, e.g., marriage rituals, turmeric is also notable for its long history of use to treat a variety of medical conditions, including inflammatory, bacterial, and fungal diseases and infections, jaundice, tumours, and ulcers among others. In light of this long history of use, it is not surprising to find that also modern biochemistry and clinical research studies show that a significant component of turmeric, curcumin, may have a multitude of therapeutic benefits, much of it attributed to the herb’s antioxidant qualities which are crucial for the prevention and treatment of, e.g., chronic inflammatory illnesses, conditions that often act as precursors for other serious diseases, including cancer and neurological disorders, such as Parkinsons and Alzheimer’s. Furthermore, investigations on the safety profile and toxicity of curcumin have shown that it is generally safe even at large dosages, although caution is necessary as curcumin also have documented anticoagulant effects. This article is focused on providing a better perspective into molecular mechanisms for possible actions along with an in-depth review of recent studies of curcumin, its beneficial role and therapeutic applications in chronic health conditions, with a focus on its cancer, inflammatory bowel disease, osteoarthritis, atherosclerosis, peptic ulcer, Covid19, psoriasis, vitiligo, and depression.

Background: Inflammatory bowel diseases (IBD) present chronic inflammatory challenges marked by increased oxidative stress. This study assessed the collective impact of Curcumin plus piperine on oxidative stress and inflammation biomarkers in mild to moderate IBD patients. Methods Patients diagnosed with CD or UC, aged ≥18 years with preserved kidney and liver functions, were randomized into three groups: placebo, Curcumin (1000 mg/day), and Curcumin plus piperine (1000 mg + 10 mg/day) for 12 weeks. Blood and fecal samples were collected to analyze oxidative stress and inflammatory markers, before and after the intervention period. Results: Curcumin plus piperine group had significantly higher serum SOD compared to the placebo group, after adjusting for sex, age, and type of IBD (4346.9 ± 879.0 vs 3614.5 ± 731.5; p=0.041). There were no significant differences in the other oxidative stress or inflammatory markers between groups. Conclusions: This study suggests that 12 weeks of Curcumin plus piperine supplementation effectively enhances the enzymatic antioxidant defense, particularly SOD, in IBD patients. These findings hold promise for managing redox imbalance in individuals with IBD, highlighting potential therapeutic benefits.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

Curcumin attracts a huge attention because of its biological properties: antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the suspension method and were characterized by dynamic and electrophoretic light scattering, transmission electron microscopy and atomic force microscopy. The average particle size was 200 nm, and ζ-potential was -4 mV. Curcumin release studies showed that nanoparticles are stable in water solution. In vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to pure curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. Median lethal dose was determined in acute toxicity assay on Zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.

The number of published studies on curcuminoids in cancer research, including its lead molecule curcumin and synthetic analogs, has been increasing substantially during the past two decades. Insights on the diversity of inhibitory effects they produced on a multitude of pathways involved in carcinogenesis and tumor progression were provided. As this wealth of data was obtained in a setting of various experimental and clinical data, this review first aimed at presenting a chronology of discoveries and an update on their complex in vivo effects. Secondly, there are many interesting questions linked to their pleiotropic effects. One of them, which is a growing research topic, relates to their ability to modulate metabolic reprogramming. This review will also cover the use of curcuminoids as chemosensitizing molecules, that can be combined with several anticancer drugs for reversing the phenomenon of multidrug resistance. Finally, current investigations in these three complementary research fields raise several important questions that will be put in the prospects for the future research related to the importance of these molecules in cancer research.

Background and Aim: Pancreatic cancer (PC) is a highly aggressive malignancy associated with low survival rates. Many chemotherapeutic regimens have been investigated for advanced unresectable and metastatic PC, but with only minimal improvement in survival and prognosis. The present study aimed to investigate the anti-cancer function of free and nano-encapsulated hydroxytyrosol (Hyd) and curcumin (Cur), and its combinations (Hyd-Cur) on the PANC-1 cell line.Methods: The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hyd and Cur were synthesized, and MTT assay was performed to evaluate cytotoxic effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur. Moreover, effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur were evaluated on viability, migration, morphological alterations, colony formation, and apoptosis on PANC-1 cell line. The mRNA expression levels of MMP2, MMP9, BAX, BCL-2, and Cas9 genes were assessed after treated PANC-1 cells with free and nano-encapsulated Hyd, Cur, and Hyd-Cur.Results: The obtained results showed that free and nano-encapsulated Hyd, Cur, and Hyd-Cur treatments significantly decreased the viability, migration, and colony formation in the PANC-1 cells. Furthermore, apoptosis rates in PANC-1 cells were increased in a concentration and time dependent manner in all of the treatment groups. Moreover, anti-proliferative activity of nano-encapsulated Hyd-Cur was significantly more than other treatments.Conclusion: According to our results, Hyd-Cur combination and nano-encapsulation therapy exerts more profound apoptotic and anti-proliferative effects on PANC-1 cell line than free Hyd or Hyd monotherapy.

We have successfully developed curcumin nanosuspension aimed for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) has shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of target site of the drug.

Furazolidone (FZD) is a synthetic nitrofuran with the antiprotozoal and antibacterial activity. The proper mechanism of FZD induced toxicity is still unclear. This study aimed to investigate the protective effect of curcumin on FZD induced oxidative stress, DNA injury and apoptosis in human hepatocyte L02 cells. The results showed that curcumin treatment significantly ameliorated FZD induced cytotoxicity, characterized by decreasing the production of reactive oxygen species (ROS) and malondialdehyde, as well as increasing superoxide dismutase, catalase activities and glutathione contents. Moreover, curcumin pretreatment significantly inhibited FZD induced the loss of mitochondrial membrane potential, the activation caspase-9 and -3 and apoptosis. Comet assay showed that curcumin attenuated FZD induced DNA injury in a dose-dependent manner. Correspondingly, curcumin markedly reversed the up-regulation of p53, Bax, caspase-9 and -3 mRNA expressions and the down-regulation of Bcl-2 mRNA (all p<0.05 or 0.01). These results reveal that curcumin protects against FZD induced oxidative stress, DNA injury and cell apoptosis via inhibiting oxidative stress and mitochondrial pathway, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, our study highlights that curcumin may be a potential way to prevent FZD-mediated oxidative DNA injury and apoptosis in human or animals.

Gold is a significant revenue source for custom copper smelters facing profitability challenges due to low treatment and refining charges, stricter regulations, and rising costs. Gold is also often blended with copper concentrates, but precise recovery rates from smelting processes are poorly documented despite gold critical economic importance. This paper aims to provide the first comprehensive estimates of gold first-pass recovery across various operational units within the copper sulfide concentrate processing flowsheet. It evaluates the effectiveness of different copper smelting and converting technologies in recovering gold. Optimizing gold first-pass recovery is especially important to enhance immediate financial returns and responsiveness to market dynamics, allowing companies to capitalize on favorable gold prices without delays. Given the absence of direct measurements for gold recovery rates, this research develops an estimation method based on understanding gold loss mechanisms during smelting. The study identifies and analyzes key input and output parameters by examining data from various copper producers. By correlating these parameters with gold loss, the research estimates gold first-pass recovery rates within the copper smelting process. Among integrated smelting-converting routes, the flash smelting to Peirce-Smith converting route achieves the highest gold first-pass recovery (98.8–99.5%), followed by the Mitsubishi continuous smelting and converting process (94.3–99.8%), bottom-blowing smelting to bottom-blowing converting (95.8%), flash smelting to flash converting (95.5%), Teniente smelting to Peirce-Smith converting (95.2%), and the Noranda continuous smelting and converting process (94.8%). The final recovery rates are expected to be higher considering the by-products internal recirculation and post-processing within the copper flowsheet. Additionally, superior gold recoveries are attributed to advanced metallurgical practices and control systems, which vary even among companies with similar technologies. The research demonstrates that copper smelting can effectively recover over 99% of gold from sulfide concentrates. Gold accumulates up to 1000 times its original concentration in anode slime during electrolytic refining, generating 5-10 kilograms of slime per ton of copper, which is further processed to recover gold and other by-products. Major smelters operate precious metal plants where recovering gold from highly concentrated anode slime is both cost-effective and efficient.

This paper (the first of a series of two) seeks to describe the experimental results of removing arsenic from dust collected in electrostatic precipitators of copper into the pyro-metallurgy gas cleaning systems. The first work corresponds to the treatment of dust contained in gas off generated in the copper Flash Smelting Furnace process (FS dust), while the second focuses on the treatment of dust generated from a Fluidized Bed Roasting Furnace (RP dust). The dust is complex sulphur-oxide-metals with concentrations of copper above 10 wt % and relatively high concentrations of silver. Due to the dust has an arsenic’s concentration above 5 wt %, makes it difficult to recover valuable metals through hydro-metallurgical processes or by direct recirculation of the dust into a smelting furnace. Thus, the development of pyrometallurgical processes aimed to reduce the concentration of arsenic in dust is the main purpose of this study, particularly the production of a material suitable for recirculation in smelting operations. The works conducted provide a detailed characterization of the dust, including Quantitative Evaluation of Minerals by Scanning Electron Microscopy (QEMSCAN), Scanning electron microscope-Energy Dispersive X-ray analysis (SEM/EDS), X-ray diffraction (XR-D), elemental chemical analysis using Atomic Adsorption (A. A.) and X-Ray Fluorescence (X-RF). By considering that arsenic volatilization requires a process of reduction-sulphidation-volatilization, the works explore the roasting of mixtures of copper concentrate/dust, sulphur/dust and pyrrhotite/dust. The degree of volatilization was determined by elemental chemical analysis of arsenic in the mixture after and before the roasting process. The results indicated the effect of parameters such as temperature, gas flow, gas composition and the ratio of mixtures (concentrate, sulphur or pyrrhotite)/dust on the volatilization of arsenic. The findings indicate that the concentration of arsenic in the FS dust can be reduced to a relatively low level (<0.5 wt %), allowing to the material to be recirculated into smelting processes.

Background: Previous studies have highlighted that copper supplementation at 200% of the recommended daily dietary allowance modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle-aged Wistar rats. Methods: In this study, young (1 month old) male Wistar rats (n/group = 10) received a diet supplemented with 6.45 mg copper/kg (100% of daily recommendation—Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200% of the daily recommendation—Group B). Results: Experimental supplementation with 200% copper modified the copper concentration in the blood (1.21-fold, p = 0.04), liver (1.15-fold, p = 0.032), and kidneys (1.23-fold, p = 0.045), potentiated the ROS formation in the aortic rings, and enhanced the sensitivity of the aortic rings to the vasodilator acetylcholine. We observed an increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase-2 in vascular relaxation. In rat kidneys, the concentrations of potassium (1.08-fold, p = 0.001) and iron (1.13-fold, p = 0.046) were higher, while, calcium (0.88-fold, p = 0.001) and chromium (0.77-fold, p = 0.005) concentrations were lower. In the rat liver, magnesium (1.06-fold, p = 0.012) was higher. No differences were observed in the concentrations of sodium, zinc, manganese, selenium, cobalt, molybdenum, and vanadium. The antioxidant activity of water- and lipid-soluble compounds; total antioxidant status in the blood; and superoxide dismutase, catalase, and malondialdehyde levels in the heart did not change. Conclusions: In young rats, prolonged supplementation with 200% copper had a lesser effect than anticipated on oxidative stress and vascular reactivity. Detailed data on the status of trace elements and their interactions in patients of different age groups are strongly required for effective nutritional and therapeutic intervention.

Impure and pure casts have collected reasonable attentions over all the world. In this paper, Aluminum (Al) and Copper (Cu) cast alloys are considered to be studied. Multiple impure and pure Al-Cu cast alloys are established under the condition of very high temperatures. Then, all of the established alloys are examined by applying mechanical tests. More specifically, tests of hardness are exploited. Moreover, different quenching conditions are employed and analyzed. These are the water, air and oil. Consistent results are separately obtained for the impure and pure materials.

The excavations carried out by the Ephorate of Antiquities of Piraeus and Islands at the cemetery in the Phaleron Delta, Attica (late 8th - 4th century B.C.), have uncovered in total 1961 burials of various types, among which the Burial 923 is of particular importance as it is the only case of secondary cremation inside a copper alloy lebes. The use of such a valuable bronze vessel, symbolizing prestige, social status and wealth, as a cinerary urn indicates the importance of this find for the interpretation of issues related to the use of the cemetery and the ritual customs of the period and makes imperative the need to preserve the object despite its significant erosion. In this paper, we will present issues related to the lifting and conservation of the bronze vessel, that was found buried within a coastal and sandy depositional environment. Also, the condition of the vessel was scientifically investigated using optical microscopy (OM), portable X-ray fluorescence (p-XRF) and X-ray diffraction (XRD) techniques. The results showed a completely mineralized bronze artefact with tin corrosion products in the core, which indicate decuprification of the copper alloy.

In this study, hybrid materials were synthesized incorporating curcumin, Cu²⁺ or Fe³⁺, and Kappa-carrageenan as a reducing agent to improve its stability, considering that curcumin has low thermal and solution stability, which limits its applications. Colorimetric analysis showed color changes in the hybrids, ultraviolet-visible spectroscopy revealed band shifts in the hybrids, and infrared analysis indicated shifts in wavenumbers, suggesting changes in the vibrational state of curcumin after bonding with metal ions. These techniques confirmed the formation of the hybrid materials. Thermogravimetric and chromatographic analyses demonstrated greater thermal and solution stability for the hybrids compared to curcumin. Additionally, the hybrid composites effectively developed natural and sebaceous latent fingerprints with good clarity and contrast on glass surfaces. Both composites performed similarly to commercial gold powder. When applied to surfaces representative of forensic scenarios, the composites were versatile, revealing sufficient fingerprint details for human identification on both porous and non-porous surfaces. Scanning electron microscopy images showed greater clarity in sebaceous and natural fingerprints developed with the Fe composite compared to the Cu composite, due to minimal interaction of Fe with the glass surface.

Curcumin is a nutraceutical known to have numerous medicinal effects including anticancer activity. However, due to its poor water solubility and bioavailability, the therapeutic impact of curcumin against cancer, especially breast cancer, has been constrained. Encapsulating curcumin into chitosan nanoparticles (CHNPs) is an effective method to increase its bioavailability as well as antitumorigenic activity. In the present study, the effect of curcumin encapsulated CHNPs (Cur-CHNPs) on cell migration, targeted homing and tumour growth was examined using in vitro and in vivo breast cancer models. Cur-CHNPs possessed monodispersed nature with long term colloidal stability, and demonstrated significant inhibition of cell viability in vitro, which was potentiated by 5-fluorouracil (5-FU). Outcomes of the in vivo imaging studies confirmed effective tumour targeting and retention ability of Cur-CHNPs, thereby suppressing breast tumour growth in mice models. Overall, the results demonstrated that Cur-CHNPs, could be an effective candidate drug formulation for management of breast cancer.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Although conventional chemotherapeutic drugs are the first line of treatment for cancer, they have numerous side effects. One of the emerging challenges in cancer treatment is drug resistance. Nat-ural compounds have proven effective against various hallmarks of cancer for their multi-target inhibition properties, but especially for their ability to synergistically bypass low bioavailability. Methods: The present study investigated the in vivo antitumor effects of a combination of two natural dietary agents, epigallocatechin-3-gallate (EGCG) from Camelia Sinensis and curcumin, a component of turmeric (Curcuma longa). We aimed to compare, for the first time in vivo, the antiangiogenic and antitumor effects of sunitinib with the combination of curcumin and EGCG in a mouse model of renal cell carcinoma (ccRCC). It was shown that they are able to inhibit cell survival, proliferation of several type of cancer, including renal cell carcinoma (ccRCC), by mod-ulating different signaling pathways and that their combination respect to single compound syn-ergistically decreased angiogenesis. Results: Herein, we highlighted that these compounds inhib-ited the growth of xenografted renal cancer in nude mice by significant inhibition of tumor vol-ume, tumor weight and CD31 expression with no signs of hepatic toxicity. Moreover, mice treated with these natural compounds showed a significant reduction in angiogenesis and an improve-ment in survival rate with p<0.05. Finally, pretreatment of mice with a diet containing 0.6% curcumin before injection of tumor cells showed a significant inhibition of tumor engraftment in 60% of mice with respect to controls and other groups. Conclusions: Taken together, our data in-dicate, for the first time, that the combination of curcumin and EGCG acts in a synergistic manner to inhibit the growth and angiogenesis of ccRCC and with less toxicity than sunitinib and provide an important rationale for future clinical development for chemoprevention and treatment of re-nal cancer.

Management of chronic inflammation and wounds has always been a key issue in the pharmaceutical and healthcare sector. Curcumin (CCM) is an active ingredient extracted from turmeric rhizomes that has antioxidant, anti-inflammatory, and antibacterial activities, thus showing significant effectiveness toward wound healing. However, its shortcomings such as poor water solubility, poor chemical stability and fast metabolic rate limit its bioavailability and long-term use. In this context, hydrogels appear to be a versatile matrix for carrying and stabilizing drugs due to the biomimetic structure, soft porous microarchitecture, and pleasant biomechanical properties. The drug loading/releasing efficiencies can also be controlled by use of highly crystalline and porous metal organic frameworks (MOFs). Here, a flexible hydrogel composed of sodium alginate (SA) matrix and CCM-loaded MOFs was constructed for long-term drug release and antibacterial activity. The morphology and physicochemical properties of composite hydrogels were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet visible spectroscopy (UV-Vis), Raman spectroscopy and mechanical property tests. The results showed that the composite hydrogel was highly twistable and bendable to mechanically comply with human skin. The as-prepared hydrogel could capture efficient CCM for slow drug release as well as effective killing of bacteria. Therefore, such composite hydrogel is expected to provide a new management system for chronic wound dressings.

Nowadays, there is evidence that bacteria can contribute to cancer formation and interfere with therapy by mediating its carcinogenesis and related infection. Moreover, it is acknowledged that microbial infections and antibiotic resistance represent severe economic and health risks to society. These facts have led to the developing of several new techniques for impeding crucial biological processes in microbial cells. One of these techniques centers on using metal-chelating agents, which can disrupt the microorganism's vital metal metabolism by obstructing metal uptake and bioavailability for critical reactions. Additionally, nanotechnology has made a wide range of nanomaterials available for possible uses in the antibacterial industry. This complex field is shaped by antimicrobial nanoparticles, also investigated as therapeutic and drug-delivery tools. Halloysite nanotubes (HNTs) are naturally occurring tubular clay nanomaterials consisting of aluminosilicate kaolin sheets rolled up several times. The aluminon and siloxane groups on the surface of HNTs facilitate the formation of hydrogen bonds with biomaterials on their surface. These properties make HNTs crucial in a wide range of applications, such as in environmental sciences, wastewater treatment, dye removal, nanoelectronics and nanocomposite fabrication, catalytic studies, coatings for glass or anti-corrosive coatings, cosmetics, flame retardants, stimulus-response, and in forensic sciences. This work aimed to produce an antibacterial material by combining the properties of halloysite nanotubes with the ability of kojic acid to chelate iron. Starting from kojic acid, a simple nucleophilic substitution involving the hydroxyl groups on the surface of the nanotubes was performed. The obtained material was characterized by IR and SEM, and its ability to chelate iron was evaluated. Finally, the capacity to load drugs such as resveratrol and curcumin was also evaluated by UV analysis. In this way, a new bio-based material that can be used as a drug carrier and antimicrobial was produced.

Corona virus disease 2019 (COVID-19) is caused by a Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), which is a positive strand RNA virus. The SARS-CoV-2 genome and its association to SAR-CoV-1 vary from ca. 66% to 96% depending on the type of betacoronavirdeae family members. With several drugs, viz. chloroquine, hydroxychloroquine, ivermectin, artemisinin, remdesivir, azithromycin considered for clinical trials, there has been an inherent need to find distinctive antiviral mechanisms of these drugs. Curcumin, a natural bioactive molecule has been shown to have a therapeutic potential for various diseases, but its effect on COVID-19 has not been explored. In this study, we show the binding potential of curcumin targeted to a variety of SARS-CoV-2 proteins, viz. spike glycoproteins (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17) along with nsp10 (PDB ID: 6W4H) and RNA dependent RNA polymerase (PDB ID: 6M71) structures. Our results indicate that curcumin has high binding affinity towards nucleocapsid and nsp 10 proteins with potential antiviral activity.

Turmeric is a popular ingredient in the cuisine of many Asian countries. Turmeric is known for its use in Chinese and Ayurvedic medicine and comes from the roots of the Curcuma longa. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin has potent anti-inflammatory and anti-carcinogenic activities. Since many anti-cancer drugs target enzymes from the steroidogenic pathway, we tested the bioactivity of curcuminoids on cytochrome P450 CYP17A1, CYP21A2, and CYP19A1 enzyme activities. Curcuminoids were extracted from turmeric with organic solvents. We conducted a cell-based assay for CYP17A1 and CYP21A2 activities using human adrenal cell line NCI-H295R. 3H-pregnenolone was used for CYP17A1 assays, and 3H-17alpha-hydroxyprogesterone was used as a substrate for CYP21A2. Curcuminoids were added at different concentrations and incubated for 24h. Steroids were separated by thin layer chromatography and analyzed by phosphorimager analysis. For CYP19A1 activity, an in vitro assay using endoplasmic reticulum from JEG3 were used with 3H-androstenedione as the substrate. Curcuminoids were incubated for 1h, and the formation of 3H-water from the androstenedione breakdown was measured by scintillation counting. When using 10 µg/ml of curcuminoids, both the 17-hydroxylase as well as 17,20 lyase activities of CYP17A1 were reduced significantly. On the other hand, CYP21A2 activity was only reduced to ~50% control. Furthermore, CYP19A1 activity was reduced to ~20% of control when using 1-100 µg/ml of curcuminoids in a dose-dependent manner. No effect on the activity of 5alpha reductase for the conversion of androstenedione to androstanedione was observed. Molecular docking studies confirmed that curcumin could dock into the active sites of CYP17A1, CYP19A1 as well as CYP21A2. In CYP17A1 and CYP19A1, curcumin docked within 2.5 Å of central heme while in CYP21A2 the distance from heme was 3.4 Å, which is still in the same range or lower than distances of bound steroid substrates. These studies show that curcuminoids may potentially cause inhibition of steroid metabolism, especially at higher dosages. The activities of CYP17A1 and CYP19A1 were inhibited by curcuminoids, which indicate potential anti-carcinogenic effects in case of prostate cancer as well as breast cancer, which can be targeted by inhibition of steroidogenesis. Also, the recent popularity of turmeric powder/curcumin as a dilatory supplement needs further evaluation for the effect of curcuminoids on steroid metabolism. Curcuminoids present in curcumin may affect activities of multiple steroid metabolizing cytochrome P450 enzymes. Computational docking suggests curcumin binds into the active sites of steroid metabolizing P450s and may serve as a model for lead discovery. Molecular structure of curcuminoids could be modified to generate better lead compounds with inhibitory effects on CYP17A1 and CYP19A1 for potential drugs against prostate cancer and breast cancer.

The latest scientific literature outlines a resilient interconnection between cancer modulation and dietary polyphenols by sphingolipid-mediated mechanisms, usually correlated with a modification of their metabolism. We aim to extensively survey this relation to show how it could be advantageous in cancer treatment or prevention by nutrients. Polyphenols, chemically characterized by polyhydroxylated phenolic structure, are well known for their pervasive pharmacological properties: anti-inflammatory, antibiotic, antiseptic, antitumor, antiallergic, cardioprotective and others. Pervasive is also their distribution in food products especially in plant foods as vegetables, cereals, legumes, fruits, nuts and beverages as wine, cider, beer, tea, cocoa. Recently, sphingolipids have been correlated with cancer by a dysregulation of their rheostat emerging as mediator of cell proliferation in cancer and modulator of chemotherapeutics.

Compounds of natural origin found in varying quantities in plant-based products constitute a highly significant category, possessing structural significance as well as the capacity to regulate oxidative processes. The activity of these compounds may be modulated by the composition of the biological milieu in which they operate, the pH of the environment, or the presence of metal cations in plants or plant extracts. This work shows the synthetic methodology and the optimization process that took place to synthesize a catechin-copper complex which demonstrated antioxidant activity tested for iron chelation ability, hydroxyl radical test and inhibition of lipoxygenase (15-LOX) activity. Antidiabetic assay was performed by determination of the alpha-amylase and alpha-glucosidase inhibition assays and the antibacterial activity showed results against Staphylococcus aureus and Candida albicans. The complex was characterized by FT-IR, UV-VIS and EDX techniques and the biological activity assays were tested in triplicate to fully confirm the activity.

Background: Alzheimer's disease (AD) is the most common cause of dementia and cognitive decline in the elderly. Although the etiology of AD is unknow, the increase of amyloid precursor protein (APP) leads to the toxic aggregation of Aβ plaques. Several factors such as hypertension, diabetes, dyslipidemia, smoking, hormonal changes, and metal exposure could increase the risk of developing AD. In this review, we will examine the role of copper (Cu) in the pathophysiology of AD, as well as the mechanisms involved in neurotoxicity and cognitive decline. Methods: This review was conducted in accordance with PRISMA guidelines. We performed a comprehensive literature analysis of the last ten years on AD and Cu. Only late-onset Alzheimer’s disease was considered; therefore, only studies on elderly people of both sexes were included. Results: A total of seven articles were picked for this review, three studies focused on non-ceruloplasmin bound Copper (non-Cp-Cu) and four on ceruloplasmin bound Copper (Cp-Cu). The results showed higher Cu concentrations in patients compared to healthy controls. Conclusion: Elevated concentrations of Cu may contribute to the progression of AD, potentially interacting with ATP7B mutations, oxidative stress, and amyloid-β plaques. Future research is needed to provide more robust evidence and better characterize the relationships between AD and Cu.

The accumulation of microorganisms, plants, algae, or small animals on wet surfaces that have a mechanical function causes biofouling, which can result in structural or other functional deficiencies. The maritime shipping industry must constantly manage biofouling to optimize operational performance, which is a common and long-lasting problem. It can occur in any metal structure in contact or submerged in ocean water, which represents additional costs in terms of repairs and maintenance. This study is focused on the production of antifouling coatings, made with nanoparticles of copper selenide (CuSe) modified with gum arabic, within a water-base acrylic polymeric matrix. During the curing of the acrylic resin, the CuSe NPs remain embedded in the resin but this does not prevent the release of ions. The coatings presented to release copper and selenium ions for up to 80 days, selenium was the element that was released the most. The adhesion of film coatings to metallic substrates showed good adhesion, scale 5B (ASTM D3359 standard). Antimicrobial activity tests show that the coatings have an inhibitory effect on Escherichia coli and Candida albicans. The effect being more noticeable when the coating is detached from the substrate and placed on a growing medium, than compared to the coating on a substrate. Scanning electron microscopy (SEM) observations show that nanostructured CuSe coatings are made up of rod-shaped and spherical particles whose range ranges from 12 to 25 nm. The Energy Dispersive X-ray spectroscopy (EDS) studies showed that the ratio of selenium nanoparticles is greater than that of copper and that their distribution is homogeneous

The exponential growth in the consumption of electronics, in combination with the reduction in their useful life, leads to a significant increase in the volume of electronic material discarded. Printed Circuit Boards (PCBs) are modules composed of ceramic, polymer and metallic materials of high economic value and with a great potential for damage to biotic and anthropic environments when inadequately discarded. The aims of this work was to study the main environmental impacts and the efficiency of mechanical operations in the electronic waste recycling process in optimizing the concentration of metallic copper. For this, the samples obtained were characterized according to their morphology and chemical composition, and subjected to physical and mechanical treatments: dismantling, grinding, separation by granulometry, density and magnetic property. The environment impacts were estimated by the Life Cycle Assessment of the pre-treatment processes, associated with copper extraction operations in WPCBs. According to the results obtained, it is possible to infer that the NM +1mm Concentrated product presents in its metallic composition around 78% of copper, which contributes to the efficiency of the hydrometallurgical extraction processes. It is noteworthy that the Concentrated class represents about 14% of copper (wt) taking into account the amount of 3.789 kg of PCB waste input material. The potential for reinsertion of the dust in the material recovery process is highlighted, given that the chemical composition of this particulate has a significant presence of metals. In general, it was found that due to the higher concentration (wt %) of the sample being allocated in the range of - 0.15mm + 0.05mm, the elements Fe (18.30%), Si (10.73%), Ca (9.21%) and Cu (8.89%) stand out regarding the participation of the elemental composition of this fraction and also regarding the general composition of the sample. Furthermore, the generation of dust during the fragmentation process, can be associated with occupational respiratory diseases when not managed. About the Life Cycle Assessment, in seven of the nine categories evaluated, crushing and screening activities accounted for more than 90% of the recorded impact values. In general, it is estimated that in the pre-treatment phase be generated 15.4 kg CO2 eq.

The development of oxidation processes with generating powerful radicals is the most interesting and thought-provoking dimension of peroxymonosulfate (PMS) activation. In this study, a magnetic spinel CuFe2O4 was successfully prepared by a facile, non-toxic, cost-efficient co-precipitation method with the synergetic effect of photocatalytic PMS oxidation against recalcitrant benzotriazole (BTA) pollutant. The high particle dispersion and large surface area (201.898 m2/g) provided a high photocatalytic activity with CuFe2O4. The obtained results from the central composite design (CCD) analysis confirmed the optimum degrading rate of BTA reached 81.4% at the optimum operational condition of CuFe2O4= 0.4 g/L, PMS= 2 mM, BTA= 20 mg/L after 70 min irradiation time. As such, the active species capture experiments revealed the presence of •OH, SO4•‒, O2•‒ and h+ species in CuFe2O4/UV/PMS system where SO4•‒ was dominated for BTA photodegradation. The combination of photocatalysis and PMS activation enhanced the consumption of metal ions in redox cycle reactions, thus preventing metal leaching and maintain the recyclability with reasonable mineralization efficiency which achieved more than 40% total organic carbon removal after four batch experiments. A retardant effect on BTA oxidation was observed with comparing the water’s common anion constituents as HCO3‒ > Cl‒ > NO3‒ > SO2‒. Results from intermediates identification showed that the transformation pathway of BTA developed as the deprotonation, hydrolysis and ring cleavage processes promoting the practical potential of photo-absorbing CuFe2O4 catalyzed PMS which can be a promising method due to convenient magnetic separation form the solution.

Metal bioaccumulation and metallothionein (MT) expression were investigated in gills and liver of the red-blooded Antarctic teleost Trematomus hansoni with the aim to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper or cadmium concentrations in the environment. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory condi-tions. The two treatments lead to a significant accumulation of both metals and an increase of gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in speci-mens exposed to Cd, but the majority of these proteins were soon oxidized, probably because they were involved in cell protection against the risk of oxidative stress, by reactive oxygen spe-cies scavenging. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species evolved in an environment characterized by natural high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming every day more toxic.

This work discussed the advantages of reducing copper in molten copper slag with low S content. FactSage calculated the distribution of copper at equilibrium under different sulfur content. The effect of sulfur content on copper recovery under different oxygen partial pressures was pointed out. The effect of sulfur content on copper recovery in the actual reduction process was explored through experimental research. Under the condition of low sulfur, the Recovery of copper and the stability of the experiment have an ideal results.

In the human body, Copper (Cu) is a major and essential player in a large number of cellular mechanisms and signaling pathways. The involvement of Cu in oxidation-reduction reactions requires close regulation of copper metabolism in order to avoid toxic effects. In many types of cancer, variations in copper protein levels have been demonstrated. These variations result in increased concentrations of intra-tumoral Cu and alterations in the systemic distribution of copper. Such alterations in Cu homeostasis may promote tumor growth or invasiveness, or even confer resistance to treatments. Once characterized, the dysregulated Cu metabolism is pinpointing several promising biomarkers for clinical use, with prognostic or predictive capabilities. The altered Cu metabolism in cancer cells and the different responses of tumor cells to Cu are strongly supporting the development of treatments to disrupt, deplete or increase Cu levels in tumors. The metallic nature of Cu, as a chemical element, is key for the development of anticancer agents via the synthesis of nanoparticles or copper-based complexes with antineoplastic properties for therapy. Finally, some of these new therapeutic strategies such as chelators or ionophores have shown promising results in a preclinical setting, while others are already in the clinic.

Predicting copper price is essential for making decisions that can affect companies and governments dependent on the copper mining industry. Copper prices follow a time series that is non-linear, non-stationary, and which have periods that change as a result of potential growth, cyclical fluctuation and errors. Sometimes the trend and cyclical components together are referred to as a trend-cycle. In order to make predictions, it is necessary to consider the different characteristics of trend-cycle. In this paper, we study a copper price prediction method using Support Vector Regression. This work explores the potential of the Support Vector Regression with external recurrences to make predictions at 5, 10, 15, 20 and 30 days into the future in the copper closing price at the London Metal Exchanges. The best model for each forecast interval is performed using a grid search and balanced cross-validation. In experiments on real data-sets, our results obtained indicate that the parameters (C, ε, γ) of the model Support Vector Regression do not differ between the different prediction intervals. Additionally, the amount of preceding values used to make the estimates does not vary according to the predicted interval. Results show that the support vector regression model has a lower prediction error and is more robust. Our results show that the presented model is able to predict copper price volatilities near reality, being the RMSE equal or less than the 2.2% for prediction periods of 5 and 10 days.

Surface Plasmon Resonance (SPR) is an attracting property of certain transition metals when they are synthesized in nano-range giving rise to promising optical applications. However, most SPR and associated applications are limited to the noble metal nanoparticles, which limits their potential due to high production cost. We report surface plasmon resonance in copper-copper oxide core-shell quantum dots synthesized via chemical route studied by using UV-Visible spectrophotometry. Tuning of the plasmonic resonance with respect to the particle diameter is achieved by an inexpensive all chemical route. Photoluminescence measurements also support the data. This size reduction leads to remarkable changes in its optical response as compared to the bulk metal. The results point towards applications of these materials in tunable SPR based biosensors.

Mining is one of the main economic activities of several developing countries as Chile. Due to the progressive fall of the ore grades and the increasingly refractory composition of minerals, concentrating plants have increased that has led to an increase in the generation of tailings. Tailings, especially those obtained in the past, have remaining copper and other valuable species in quantities that can potentially be recovered, such as gold, silver, vanadium and rare earth elements. This transforms this abundant waste into a potential source of precious or strategic metals for secondary mining. One of the techniques of solid-liquid separation that allows the processing of solutions with low concentrations of metals corresponds to the adsorption, and more recently the biosorption, which is based on the use of biological matrices that do not constitute an environmental liability after application. Biosorption occurs as a consequence of the wide variety of active functional groups present in the different types of biomass. Bacterial, fungal, plant and algal biomasses have been described as biosorbents, mainly for the treatment of diluted and simple solutions. This work aims to recover copper from leached tailings using biomass of the red algae Gracilaria chilensis as a biosorbent. The tailing samples were taken from an abandoned deposit in the north of Chile and after an acid leaching copper was biosorbed, for which the kinetics of adsorption and the equilibrium isotherms were studied, applying the Freundlich and Langmuir models. Operational parameters such as adsorbent dose, pH and initial metal concentration were studied.

This article presents the copper ions adsorption process using an activated carbon from winemaking wastes. The pH, temperature, activated carbon amount and initial copper concentration were varied based on a full factorial 2^k experimental design. Kinetic and thermodynamic studies were also carried out. The adsorption kinetics was found follow a pseudo-second-order model. The adsorption data fit better to the Langmuir isotherm. The ANOVA demonstrated that both pH of the solution and activated carbon dosage had the greatest influence on copper adsorption. The activation energy was -32 kJ·mol^-1 suggesting that the copper adsorption is a physic-sorption process. The best fit to a linear correlation was the moving boundary equation that controls the kinetics for the adsorption copper ions onto the activated carbon. The X-ray photoelectron spectroscopy (XPS) results reveal the existence of different copper species (Cu²⁺, Cu⁺ and or Cu⁰) on the surface of the carbonaceous adsorbent after the adsorption, which could suggest a simultaneous reduction process.

One of the largest in the archipelago silver-copper mineralisation at Mount Sigurdf′ellet in West Spitsbergen Island was found in 1990 by Russian geologists. Firstly genesis was caused exclusively with hydrothermal ore migration of a substance from the enclosing sandstone and siltstone of the Devonian age. But subsequent work on the ore and nearest rocks of the basement gave a new factual material on the geochemical characteristics of potential sources of metals and found new for this mineral occurrence - gold mineralization. Similarity of geochemical associations of Sigurd ore occurrence with nearby upper Proterozoic marble as the first likely source of ore substance and the second - caused by carbonate-containing streaks in Low Devonian sediments. Ore-formation, probably due to repeated hydrothermal processes and was completed in a period of tectono-magmatic activity in Jurassic-Cretaceous time.

In this study, the corrosion performances of ammonium copper quat (ACQ) and boric acid (BA) wood preservatives were investigated, with micronized copper quat (MCQ) and nano boron (NB) used as reference materials. In the study, Scots pine (Pinus sylvestris L.) wood samples were impregnated according to the full-cell process method with ACQ at 2.4% concentration, BA at 4% and MCQ and NB at 1%. The ACQ- and BA-impregnated samples were then impregnated for a second time using five different water-repellent materials: tall oil, linseed oil, sodium silicate, methyl hydrogen silicone and N'-N- (1, 8-Naphthalyl) hydroxylamine. Polyethylene glycol (PEG) 600 and aluminum sulfate were introduced as single impregnations in the form of homogeneous mixtures with the ACQ and BA. The corrosion properties of the impregnated and control samples, including metal weight loss (MWL) and corrosion depth, were examined. As a result, the MWL values of the ACQ-impregnated samples showed an increase compared to the control group. The MWL values of the MCQ-impregnated samples were lower than those of the samples impregnated with ACQ, whilst the MWL values of the BA-impregnated samples were higher than those of the samples impregnated with NB.

Polymeric nanoparticles (NPs) have garnered significant interest due to their potential in drug delivery. Specifically, nanopolymers functionalized with molecules such as proteins or peptides serve as versatile vehicles for this purpose. Curcumin (Cur) is a widely studied anticancer compound known for its positive effects on human health. Nevertheless, its insolubility and low bio-distribution hinder the exploitation of its beneficial traits. In this study, our team developed a nanodelivery system using a nanopolymer called poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG), functionalized with A6 peptide to enable targeted delivery of Cur. The designed system exhibited favorable characteristics, including a stable zeta potential of -13.8 mV, a small size of 76.4 nm, uniform surface morphology, and high hydrophilicity with a contact angle of 31.53°. Additionally, the targeted delivery system demonstrated high encapsulation efficiency (EE%) (93 ± 0.89%), drug loading (DL%) (16.7 ± 0.9%), and a slow and gradual release profile with a release of approximately 83.1 ± 0.12%. The MTT assay results showed significant cell death in MDA-MB-231 cancer cells (IC₅₀ = 21.3 ± 1.57 µM) when treated with the Cur-NPs-A6 formulation, while the toxicity of the designed NPs was reduced on non-cancerous MCF-10A cells. Moreover, both the RT-qPCR and invasion assays demonstrated the system's effectiveness in activating apoptosis pathways and inhibiting cell invasion. These findings suggest that the engineered intelligent delivery system, equipped with the A6 peptide, which has a strong affinity for CD44 (a protein with increased expression in malignancy), could be an exceptionally effective strategy for cancer treatment.

Relapsed leukemia following initial therapeutic response and remission is difficult to treat and causes high patient mortality. Leukemia relapse is due to residual quiescent leukemia cells that escape conventional therapies and later reemerge. Eliminating not only growing but quiescent leukemia cells is critical to effectively treating leukemia and preventing its recurrence. Such therapeutic agents, however, are lacking in the clinic. Here we report that a 4-arylmethyl derivative of the natural anticancer compound curcumin demonstrates a dual effect in eliminating both growing and quiescent leukemia cells. This curcumin derivative, C212, on the one hand, inhibits growing leukemia cells at a higher efficacy than curcumin by inducing apoptosis and cell cycle arrest; it, on the other hand, kills quiescent leukemia cells that are resistant to conventional chemotherapy drugs. Furthermore, C212 drives leukemia cells into and kills them at deep quiescence, avoiding the potential risk associated with awaking therapy-resistant subpopulation of quiescent leukemia cells. Lastly, we show that C212 induces apoptosis and drives cells into deep dormancy at least partially by binding to and inhibiting Hsp90, leading to client protein degradation and protein aggregation. Further elucidating the molecular mechanisms underlying the dual function of C212 in eliminating both growing and quiescent leukemia cells will aid the development of novel therapies against leukemia relapse.

Endogenous androgens are pivotal in the development and progression of prostate cancer (PC). We investigated nanoparticle formulations of curcumin and piperine in modulating steroidogenesis within PC cells. Using multiple PC cell lines (LNCaP, VCaP, DU145 and PC3) we studied the effects of curcumin, piperine, and their nanoparticle formulations—curcumin nanoparticles, piperine nanoparticles, and curcumin-piperine nanoparticles (CPN)—on cell viability, migration, and steroid biosynthesis. Curcumin and its nanoparticle formulations significantly reduced cell viability in PC cells, with curcumin-piperine nanoparticles showing the highest efficacy. These treatments also inhibited cell migration, with CPN exhibiting the most pronounced effect. In assays for steroid biosynthesis, curcumin and its nanoparticle formulations, as well as piperine and its nanoparticles, selectively inhibited 17α-hydroxylase and 17,20-lyase activities of cytochrome P450 17A1 (CYP17A1). Abiraterone, a CYP17A1 inhibitor, displayed a broader inhibition of steroid metabolism including cytochrome P450 21-hydroxylase activity, whereas curcumin and piperine provided a more targeted inhibition profile. Analysis of steroid metabolites by liquid chromatography-mass spectrometry revealed that CPN caused significant reduction of androstenedione and cortisol, suggesting potential synergistic effects. In conclusion, nanoformulations co-loaded with curcumin and piperine offer an effective approach to targeting steroidogenesis and could be promising candidates for therapies aimed at managing androgen-dependent PC.

New allyl derivative of curcumin containing three allyl groups (1E,6E)-4-allyl-1,7-bis(4’-allyloxy-3’-methoxyphenyl)hepta-1,6-diene-3,5-dione was synthesized by the reaction of curcumin with the excess of allyl bromide in the presence of K2CO3 in acetone under reflux. The triple allylated curcumin was characterized by 1H and 13C NMR spectroscopy and single-crystal X-ray diffraction study.

Curcumin, extracted from the Curcuma longa rhizome, has gained substantial attention for its anti-inflammatory, antioxidant, and neuroprotective properties. Despite these potential benefits, its low bioavailability limits its usage and potential in clinical settings. To overcome these limitations, novel formulations have been developed using liposomal, nanoparticular and micellization technologies to improve bioavailability. The current randomized, double-blind, crossover, pharmacokinetic study compared AQUATURM^®, a novel, patented water-soluble formulation, to another commercially available and widely used curcumin supplement in 12 human subjects over a 12-hour period separated by a 7-day washout period. Plasma samples were analyzed by tandem mass spectrometry detection (UPLC-MS/MS). The area under the plasma concentration-time curve indicated that the bioavailability of AQUATURM^® was over 7-fold greater than that of the other curcumin supplement, reaching concentrations up to 20 ng/mL for up to 12-hours. This study demonstrates AQUATURM^®’s superior bioavailability to that of another, conventional, widely used curcumin supplement.

Zein protein (ZP) is the major storage protein of corn (maize). It is safe, biodegradable, edible, and characterized by unique amphiphilic and self-assembly properties. We exploited these properties to prepare stable ZP microcapsules by oil-in-water ultrasound-assisted emulsification. The opti-mal experimental conditions were determined in terms of the sonication frequency, applied acoustic power, sonication time, protein concentration and temperature. The morphology and stability of ZP microcapsules were characterized by optical spectroscopy and microscopy tech-niques. We found that a thick ZP outer layer protects the inner oily phase from internal/external diffusion, and enables the microencapsulation of Curcumin, a very active anti-inflammatory and nutraceutical agent.

Although there are numerous available immunomodulators, those of natural origin would be preferable based on their safety profile and effectiveness. The research and clinical interest in immunomodulators have increased in the last decades, especially in the immunomodulatory properties of plant-based therapies. Innovative technologies and extensive study on immunomodulatory natural products, botanicals, extracts, and active moieties with immunomodulatory potential could provide us with valuable entities to develop as novel immunomodulatory medicines to enhance current chemotherapies. This review focuses on plant-based immunomodulatory drugs that are currently in clinical studies. However, further studies in this area are of utmost importance to obtain complete information about the positive effects of medicinal plants and their chemical components and molecules as an alternative to combatting various diseases and/or prevention.

Dermal penetration is considered to mainly occur via passive diffusion. Therefore, a high concentration gradient of dissolved active ingredient between formulation and skin is needed to achieve an effective dermal penetration. The concentration gradient between formulation and skin can be changed by changing the amount of dissolved active ingredient in the formulation. In case of poorly soluble active ingredients this can be achieved by using nanosized drug material instead of larger sized material. The smaller size and the resulting larger surface increase the kinetic solubility and thus increase the concentration gradient of dissolved active ingredient between formulation and skin, which then results in an increased dermal penetration. In this study we demonstrated that the concentration gradient between formulation and skin can also be influenced by the number of particles being present in the formulation and by the dose (volume of formulation) applied to the skin. Particles of undissolved active ingredient are known to act as a reservoir by releasing dissolved molecules in the liquid phase of the formulation. It could now be demonstrated that the particles - once the liquid in which they are dispersed evaporates - can connect to the skin via an aqueous meniscus. The aqueous meniscus contains dissolved active ingredient and therefore creates a small local spot with a locally high concentration gradient and improved dermal penetration. Therefore, the dermal penetration can be increased with formulations that contain high amounts of particles. This can be achieved by applying formulations with high numbers of particles and/or by applying larger volumes of particle containing formulations to the skin.

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

Microbial infections in wounds can significantly delay the healing process, with bacteria often forming protective biofilms that shield them from external threats. In this study, we evaluated the impact of copper oxide-impregnated wound dressings (referred to as COD) on a bacterial mixture comprising common gram-positive and gram-negative wound pathogens encased in biofilm. The bacterial mix was exposed to COD or control dressings for 0, 1, 2, and 3 hours, and the effects were analyzed using scanning electron microscopy. After just 1 hour of exposure to COD, notable leakage of bacterial cytoplasmic contents was observed. By the 3-hour mark, the gram-negative bacteria exhibited formation of holes in their cell walls, while gram-positive bacteria showed a reduction in cell width. These findings demonstrate the ability of COD to effectively kill bacteria, even when protected by biofilm, supporting clinical observations of its efficacy in managing infected wounds.

Cyclic voltammetry can be applied as the reliable method for the determination of chloride ions in a range from several to couple hundred ppm. Since the standard potential of chloride ion/gaseous chlorine is 1.36 V vs NHE the efficient oxidation of Cl- ion occurs at very positive electrode potentials, usually higher than + 1.7 V vs NHE electrode. It is possible to observe this phenomenon only at noble-metal or inert carbon electrodes. Many other solutes, usually organic compounds, are often oxidized at this potential. This is the reason why determination of Cl- content directly from increase of the oxidation current is not reliable and can lead to overestimated values. However, gaseous chlorine, generated at positive potential dissolves in the analyzed solution and can be reduced in the reverse scan of cyclic voltammetric curve. Optimization of the experimental procedure using the statistical tools allowed for the development of the improved method for the direct quantification of chloride ions in acid copper electroplating baths. Under the proposed experimental conditions, the calibration curve (Cl2 voltammetric reduction current vs. chloride ions concentration) is represented by the linear model for the concentration of chlorides ranging from 10 to 200 mg/dm3.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

The effects of rare earth Ce on the microstructure and properties of cast pure copper were investigated through thermodynamic calculations, XRD analysis, mechanical testing, metallographic microscopy, and scanning electron microscopy (SEM). The experimental results demonstrate that the reaction between rare earth Ce and oxygen as well as sulfur in copper exhibits a significantly negative Gibbs free energy value, indicating a strong thermodynamic driving force for deoxidation and desulfurization reactions. Ce is capable of removing trace amounts of O and S from copper. Moreover, the maximum solid solubility of Ce in Cu falls within the range of 0.009% to 0.01%. Furthermore, Ce can refine columnar grains while enlarging equiaxed grains in as-cast copper.Upon addition of rare earth Ce, the tensile strength increased by 8.45%, elongation increased by 12.1%, and microhardness rose from 73.5HV to 81.2HV-an increase of 10.5%. Overall, rare earth Ce has been found to enhance both the microstructure and mechanical properties of cast pure copper.

Copper oxide nanoparticles (CuONPs) were synthesized using an eco-friendly method and their antimicrobial and biocompatibility properties were determined. The supernatant and extract of the fungus Ganoderma sessile yielded small, quasi-spherical NPs with an average size of 4.5 ± 1.9 nm and 5.2 ± 2.1 nm, respectively. CuONPs showed antimicrobial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Minimum inhibitory concentration (MIC) for E. coli and S. aureus was 15.9 µg/mL for nanoparticles (NPs) using the supernatant (CuONPs-S) and 16.5 µg/ml for NPs using the extract (CuONPs-E). Lower concentrations were required for P. aeruginosa inhibition. Ultrastructural analysis revealed the presence of the small CuONPs all through the bacterial cells. Finally, the toxicity of CuONPs was analyzed in three mammalian cell lines: hepatocytes (AML-12), macrophages (RAW 264.7) and kidney (MDCK). Low concentrations (<15 µg/ml) of CuONPs-E were non-toxic to kidney cells and macrophages, and the hepatocytes were the most susceptible to CuONPs-S. The results obtained suggest that the CuONPs synthesized using the extract of the fungus G. sessile, could be further evaluated for the treatment of superficial infectious diseases.

Organic Coatings have potential applications in the prevention of metal corrosion in an aqueous solution. The protective effect of SEBS coated copper corrosion in NaCl 3% solution was investigated by using electrochemical methods. The main objective of this work is to find the optimal conditions of the protocol immersion to evaluate the effects of SEBS ratio and two-immersion time on the anticorrosive behaviour of copper in 3 wt % NaCl solution in order to determine the best conditions to produce a protective SEBS film on the copper surface. Response Surface Methodology (RSM) is used as an optimization method. The study’s findings show the combination of three environmental factors that minimize corrosion rate. The Box-Behnken Design (BBD) is working perfectly for the statistical significance of the model (ANOVA test). This analysis calculates the contribution value of each parameter in changing the value of the corrosion rate (CR) in not only individual but also synergistic cases. The optimized parameters were found to be a 2.17% of SEBS ratio, 20 min of immersion 1, and 21 min of immersion 2. The electrochemical impedance spectroscopy tests confirmed the results.

Abstract Purpose Since their introduction, intrauterine devices (IUDs) have been associated with various complications. Avery rare complication is the perforation of the cervix by the strings of the IUD. Purpose of the current study is to present a novel case of cervical perforation by the strings of a copper IUD and to perform a systematic review of the literature. Materials and Methods The patient a 43-year-old attended the gynecology clinic in order to remove her copper IUD. Speculum examination revealed that both the strings of the IUD perforated the anterior lip of the cervix. Management options were offered, the patient opted for a hysteroscopic removal. We searched the electronic databases: MEDLINE, Cochrane Library,Google Scholar,EBSCO for similar cases. Results Electronic search yielded 1821 articles; 8 were selected for inclusion. Mean age of the women was 35,37±7,781, range (26-47) years. One woman (12.5%) was nulligravida;3 women were multigravida (37,5%). Seven women (87,5%) were asymptomatic. Three IUDs (37,5%) were LNG-IUS; 5 IUDs (62,5%) contained copper. Conclusions Cervical perforation by the strings of IUD is an extremely rare clinical entity. It is asymptomatic in general and in most cases the strings of the IUD may be returned back to the endocervical canal after surgical maneuvers.

Copper toxicity has been a selective pressure on the sea-ice bacteria due to its widespread occur-rence in Antarctica. Here, with a combined biochemical and metabolomic approach, the Cu2+ ad-aptation mechanisms of Antarctic bacteria were analyzed. Heavy metal resistance pattern of Pb2+ > Cu2+ > Cd2+ > Hg2+ > Zn2+ was observed. Copper treatment did increase the activity of antioxidants and enzymes, maintaining cellular redox state balance and normal cell division and growth. Metabolomics analysis demonstrated that fatty acids, amino acids, and carbohydrates played dominant roles in copper stress adaptation. The results indicated that the adaptation mechanisms of strain O5 to copper stress included protein synthesis and repair, accumulation of organic per-meable substances, up-regulation of energy metabolism, and formation of fatty acids. This study increases the resistance mechanism understanding of Antarctic strains to heavy metals in extreme environments.

Long-term changes in nanoparticles of copper-silver bimetallic systems on natural clinoptilolite obtained by ion exchange of Cu2+ and Ag+, and then reduced at different temperatures, have been studied. Even after storage under ambient conditions, XRD and UV-Vis diffuse reflectance spectra indicate the presence of nanospecies of reduced copper and silver. Scanning Electron Microscopy of aged bimetallic samples, reduced at the highest temperature (450oC) and the primary samples for their preparation, also aged, showed the presence of silver nanoparticles with a size of about 100 nm. They are formed in the initial ion-exchanged sample (without reduction) due to the degradation of Ag+ ions. The nanoparticles in the reduced sample are larger; in both samples they are evenly distributed over the surface. The presence of silver affects the stability and the mechanism of decomposition/oxidation of reduced copper nanospecies, and this stability is higher in bimetallic systems. The decomposition pattern of recently reduced species includes the formation of smaller nanoparticles and few-atomic clusters. This can occur, preceding the complete oxidation of Cu to ions. Quasi-colloidal silver, which is present in fresh bimetallic samples reduced at lower temperatures, transforms after aging into Ag8 clusters, which indicates the stability of these nanospecies on natural clinoptilolite.

There is an increasing interest in applying environmentally-friendly materials in wood protection technology. This include the use of less toxic active ingredients, as well as better fixation. This study investigates the formulation based on the combination of copper and Saqez resin on the physical and biological resistance properties of poplar wood. Samples were treated by either copper-ethanolamine (Cu/MEA) and/or Saqez resin at various treatment levels. A vacuum pressure procedure was applied. The retention, weight percent gain, water absorption, volumetric swelling, and decay resistance of the samples were then determined. The highest retention and weight percent gain were obtained at the samples treated with the combination of copper-based system and Saqez resin. Additionally, the combination of the copper and Saqez improved the physical properties and decay-resistance against white-rot fungus Trametes versicolor.

Copper smelting slag is a solution of molten oxides created during the copper smelting and refining process, and about 1.5 million tons of copper slag is generated annually in Korea. Oxides in copper smelting slag include ferrous (FeO), ferric oxide (Fe­₂O₃), silica (SiO­₂ from flux), alumina (AI₂O₃), calcia (CaO) and magnesia (MgO). Main oxides in copper slag, which iron oxide and silica, exist in the form of fayalite (2FeO·SiO₂). Since the copper smelting slag contains high content of iron, and copper and zinc. Common applications of copper smelting slag are the value added products such as abrasive tools, roofing granules, road-base construction, railroad ballast, fine aggregate in concrete, etc., as well as the some studies have attempted to recover metal values from copper slag. This research was intended to recovery Fe-Cu alloy, raw material of zinc and produce reformed slag like a blast furnace slag for blast furnace slag cement from copper slag. As a results, it was confirmed that reduction smelting by carbon at temperatures above 1400°С is possible to recover pig iron containing copper from copper smelting slag, and CaO additives in the reduction smelting assist to reduce iron oxide in the fayalite and change the chemical and mineralogical composition of the slag. Copper oxide in the slag can be easily reduced and dissolved in the molten pig iron, and zinc oxide is also reduced to a volatile zinc, which is removed from the furnace as the fumes, by carbon during reduction process. When CaO addition is above 5wt.%, acid slag has been completely transformed to calcium silicate slag and observed like blast furnace slag.