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1.
Biomaterials ; 312: 122720, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39084098

ABSTRACT

Mesenchymal stem cells (MSCs) are expected to be useful therapeutics in osteoarthritis (OA), the most common joint disorder characterized by cartilage degradation. However, evidence is limited with regard to cartilage repair in clinical trials because of the uncontrolled differentiation and weak cartilage-targeting ability of MSCs after injection. To overcome these drawbacks, here we synthesized CuO@MSN nanoparticles (NPs) to deliver Sox9 plasmid DNA (favoring chondrogenesis) and recombinant protein Bmp7 (inhibiting hypertrophy). After taking up CuO@MSN/Sox9/Bmp7 (CSB NPs), the expressions of chondrogenic markers were enhanced while hypertrophic markers were decreased in response to these CSB-engineered MSCs. Moreover, a cartilage-targeted peptide (designated as peptide W) was conjugated onto the surface of MSCs via a click chemistry reaction, thereby prolonging the residence time of MSCs in both the knee joint cavity of mice and human-derived cartilage. In a surgery-induced OA mouse model, the NP and peptide dual-modified W-CSB-MSCs showed an enhancing therapeutic effect on cartilage repair in knee joints compared with other engineered MSCs after intra-articular injection. Most importantly, W-CSB-MSCs accelerated cartilage regeneration in damaged cartilage explants derived from OA patients. Thus, this new peptide and NPs dual engineering strategy shows potential for clinical applications to boost cartilage repair in OA using MSC therapy.


Subject(s)
Cell Differentiation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Nanoparticles , Osteoarthritis , Peptides , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Animals , Osteoarthritis/therapy , Osteoarthritis/pathology , Nanoparticles/chemistry , Humans , Cell Differentiation/drug effects , Peptides/chemistry , Mesenchymal Stem Cell Transplantation/methods , Chondrogenesis/drug effects , Mice , SOX9 Transcription Factor/metabolism , SOX9 Transcription Factor/genetics , Cartilage, Articular/pathology , Cartilage, Articular/drug effects , Bone Morphogenetic Protein 7/chemistry , Bone Morphogenetic Protein 7/pharmacology , Tissue Engineering/methods , Regeneration/drug effects
2.
Biomaterials ; 313: 122805, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39250865

ABSTRACT

Copper (Cu), an essential micronutrient with redox properties, plays a pivotal role in a wide array of pathological and physiological processes across virtually all cell types. Maintaining an optimal copper concentration is critical for cellular survival: insufficient copper levels disrupt respiration and metabolism, while excess copper compromises cell viability, potentially leading to cell death. Similarly, in the context of cancer, copper exhibits a dual role: appropriate amount of copper can promote tumor progression and be an accomplice, yet beyond befitting level, copper can bring about multiple types of cell death, including autophagy, apoptosis, ferroptosis, immunogenic cell death, pyroptosis, and cuproptosis. These forms of cell death are beneficial against cancer progression; however, achieving precise copper regulation within tumors remains a significant challenge in the pursuit of effective cancer therapies. The emergence of nanodrug delivery systems, distinguished by their precise targeting, controlled release, high payload capacity, and the ability to co-deliver multiple agents, has revitalized interest in exploiting copper's precise regulatory capabilities. Nevertheless, there remains a dearth of comprehensive review of copper's bidirectional effects on tumorigenesis and the role of copper-based nanomaterials in modulating tumor progression. This paper aims to address this gap by elucidating the complex role in cancer biology and highlighting its potential as a therapeutic target. Through an exploration of copper's dualistic nature and the application of nanotechnology, this review seeks to offer novel insights and guide future research in advancing cancer treatment.


Subject(s)
Copper , Nanostructures , Neoplasms , Copper/chemistry , Humans , Animals , Nanostructures/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Cell Death/drug effects
3.
J Environ Sci (China) ; 148: 476-488, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39095182

ABSTRACT

In this study, non-thermal plasma (NTP) was employed to modify the Cu/TiO2 adsorbent to efficiently purify H2S in low-temperature and micro-oxygen environments. The effects of Cu loading amounts and atmospheres of NTP treatment on the adsorption-oxidation performance of the adsorbents were investigated. The NTP modification successfully boosted the H2S removal capacity to varying degrees, and the optimized adsorbent treated by air plasma (Cu/TiO2-Air) attained the best H2S breakthrough capacity of 113.29 mg H2S/gadsorbent, which was almost 5 times higher than that of the adsorbent without NTP modification. Further studies demonstrated that the superior performance of Cu/TiO2-Air was attributed to increased mesoporous volume, more exposure of active sites (CuO) and functional groups (amino groups and hydroxyl groups), enhanced Ti-O-Cu interaction, and the favorable ratio of active oxygen species. Additionally, the X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) results indicated the main reason for the deactivation was the consumption of the active components (CuO) and the agglomeration of reaction products (CuS and SO42-) occupying the active sites on the surface and the inner pores of the adsorbents.


Subject(s)
Copper , Hydrogen Sulfide , Oxidation-Reduction , Titanium , Titanium/chemistry , Adsorption , Copper/chemistry , Hydrogen Sulfide/chemistry , Air Pollutants/chemistry , Plasma Gases/chemistry , Models, Chemical
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125008, 2025 Jan 05.
Article in English | MEDLINE | ID: mdl-39182400

ABSTRACT

N-acetyl-L-cysteine (NAC) as a class of thiols is commonly used in the treatment of lung diseases, detoxification and prevention of liver damage. In this paper, 4-mercaptobenzoic acid (4-MBA) coated and polyvinylpyrrolidone (PVP) attached copper nanoclusters (4-MBA@PVP-CuNCs) were successfully synthesized using a simple one-pot method with an absolute quantum yield of 10.98 %, and its synthetic conditions (like effects of single/double ligands and temperature) were studied intensively. Then Hg2+ could quench the fluorescence of the 4-MBA@PVP-CuNCs and its fluorescence was restored with the addition of NAC. Based on the above principles, an off-on switching system was established to detect NAC. That is, the 4-MBA@PVP-CuNCs-Hg probe was prepared by adding Hg2+ to switch off the fluorescence of the CuNCs by static quenching, and then NAC was added to switch on the fluorescence of the probe based on the chelation of NAC and Hg2+. Moreover, the effects of metal ion types and mercury ion doses for the probe construction were also further discussed. The method showed excellent linearity in the range of 0.05-1.25 µM and low detection limit of 16 nM. Meanwhile, good recoveries in real urine, tablets and pellets were observed, which proved the reliability of the method and provided a convenient, fast and sensitive method for NAC detection.


Subject(s)
Acetylcysteine , Copper , Limit of Detection , Metal Nanoparticles , Spectrometry, Fluorescence , Sulfhydryl Compounds , Acetylcysteine/chemistry , Acetylcysteine/urine , Copper/chemistry , Copper/analysis , Spectrometry, Fluorescence/methods , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/analysis , Ligands , Metal Nanoparticles/chemistry , Mercury/analysis , Mercury/urine , Humans , Fluorescent Dyes/chemistry , Povidone/chemistry , Benzoates/chemistry , Polymers/chemistry
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124988, 2025 Jan 05.
Article in English | MEDLINE | ID: mdl-39163772

ABSTRACT

Two quinoxaline dyes utilized in copper-electrolyte-based dye-sensitized solar cells (Cu-DSSCs) are theoretically investigated to analyze the impact of alkyl chains on dye performance. The investigation shows that ZS4, known for its record efficiency of up to 13.2 %, exhibits higher electron coupling and fewer binding sites for dye-[Cu(tmby)2]2+ interaction compared to ZS5. Contrary to common belief, alkyl chains are found to not only provide shielding but also hinder the interaction between dye and [Cu(tmby)2]2+ by influencing the optimal conformation of dyes, thereby impeding the charge recombination process. It is crucial to consider the influence of alkyl chains on dye conformation when discussing the relationship between dye structure and performance, rather than oversimplifying it as often done traditionally. Building on these findings, eight dyes are strategically designed by adjusting the position of the alkyl chain to further decrease charge recombination compared to ZS4. Theoretical evaluation of these dyes reveals that changing the alkyl chain on the nitrogen atom from 2-ethylhexyl (ZS4) to 1-hexylheptyl (D3-2) not only reduces the charge recombination rate but also enhances light harvesting ability. Therefore, D3-2 shows potential as a candidate for experimental synthesis of high-performance Cu-DSSCs with improved efficiency.

6.
J Environ Sci (China) ; 149: 476-487, 2025 Mar.
Article in English | MEDLINE | ID: mdl-39181660

ABSTRACT

Herein, three supported catalysts, CuO/Al2O3, CeO2/Al2O3, and CuO-CeO2/Al2O3, were synthesized by the convenient impregnation method to reveal the effect of CeO2 addition on catalytic performance and reaction mechanism for toluene oxidation. Compared with CuO/Al2O3, the T50 and T90 (the temperatures at 50% and 90% toluene conversion, respectively) of CuO-CeO2/Al2O3 were reduced by 33 and 39 °C, respectively. N2 adsorption-desorption experiment, XRD, SEM, EDS mapping, Raman, EPR, H2-TPR, O2-TPD, XPS, NH3-TPD, Toluene-TPD, and in-situ DRIFTS were conducted to characterize these catalysts. The excellent catalytic performance of CuO-CeO2/Al2O3 could be attributed to its strong copper-cerium interaction and high oxygen vacancies concentration. Moreover, in-situ DRIFTS proved that CuO-CeO2/Al2O3 promoted the conversion of toluene to benzoate and accelerated the deep degradation path of toluene. This work provided valuable insights into the development of efficient and economical catalysts for volatile organic compounds.


Subject(s)
Cerium , Copper , Oxidation-Reduction , Toluene , Toluene/chemistry , Catalysis , Copper/chemistry , Cerium/chemistry , Models, Chemical , Air Pollutants/chemistry
7.
Angew Chem Int Ed Engl ; : e202414810, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322938

ABSTRACT

Developing ionic copper-iodine clusters with multiple emitting is crucial for enriching lighting and display materials with various colors. However, the luminescent properties of traditional ionic copper-iodine clusters are often closely associated with low-energy cluster-centered triplet emission, which will redshift further as the Cu···Cu bond length decreases. This article utilizes a pressure-treated strategy to achieve an anomalous pressure-induced blue-shifted luminescence phenomenon in ionic Cu4I6(4-dimethylamino-1-ethylpyridinium)2 crystals for the first time, which is based on dominant through-space charge-transfer (TSCT). Herein, we reveal that the more advantageous through-space interactions in the competition between coprophilic interactions and through-space interactions can lead to a blue-shifted luminescence. High-pressure angle-dispersive X-ray diffraction and high-pressure infrared experiments show that the enhanced through-space interactions mainly originate from forming new intermolecular C-H···I hydrogen bonds and the enhancement of van der Waals interactions between organic cations and anionic clusters. Theoretical calculations and experimental studies of excited-state dynamics confirm that the blue-shifted emission is due to the increased energy gap between the excited triplet and ground states caused by the electron delocalization under stronger through-space interactions. This work deepens previous understanding and provides a new avenue to design and synthetic ionic copper-iodine clusters with high-energy TSCT emission.

8.
Int J Biol Sci ; 20(12): 4872-4887, 2024.
Article in English | MEDLINE | ID: mdl-39309446

ABSTRACT

Breast cancer (BC) persists as a highly prevalent malignancy in females, characterized by diverse molecular signatures and necessitating personalized therapeutic approaches. The equilibrium of copper within the organism is meticulously maintained through regulated absorption, distribution, and elimination, underpinning not only cellular equilibrium but also various essential biological functions. The process of cuproptosis is initiated by copper's interaction with lipoylases within the tricarboxylic acid (TCA) cycle, which triggers the conglomeration of lipoylated proteins and diminishes the integrity of Fe-S clusters, culminating in cell demise through proteotoxic stress. In BC, aberrations in cuproptosis are prominent and represent a crucial molecular incident that contributes to the disease progression. It influences BC cell metabolism and affects critical traits such as proliferation, invasiveness, and resistance to chemotherapy. Therapeutic strategies that target cuproptosis have shown promising antitumor efficacy. Moreover, a plethora of cuproptosis-centric genes, including cuproptosis-related genes (CRGs), CRG-associated non-coding RNAs (ncRNAs), and cuproptosis-associated regulators, have been identified, offering potential for the development of risk assessment models or diagnostic signatures. In this review, we provide a comprehensive exposition of the fundamental principles of cuproptosis, its influence on the malignant phenotypes of BC, the prognostic implications of cuproptosis-based markers, and the substantial prospects of exploiting cuproptosis for BC therapy, thereby laying a theoretical foundation for targeted interventions in this domain.


Subject(s)
Breast Neoplasms , Copper , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Copper/metabolism , Disease Progression
9.
Acta Pharm Sin B ; 14(9): 4059-4072, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39309486

ABSTRACT

Copper-based nanomaterials demonstrate promising potential in cancer therapy. Cu+ efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione, initiating chemical dynamic therapy (CDT) and ferroptosis. Cuproptosis, a newly identified cell death modality that represents a great prospect in cancer therapy, is activated. However, active homeostatic systems rigorously keep copper levels within cells exceptionally low, which hinders the application of cooper nanomaterials-based therapy. Herein, a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is developed. The Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment, further releasing RNP and Cu+. The liberated Cu+ triggered a Fenton-like reaction for CDT and partially transformed to Cu2+, consuming intracellular GSH and initiating cuproptosis and ferroptosis efficiently. Meanwhile, the release of RNP effectively reduced the expression of copper transporter ATP7A, subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT, cuproptosis, and ferroptosis. Such tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

10.
Theranostics ; 14(14): 5371-5387, 2024.
Article in English | MEDLINE | ID: mdl-39310112

ABSTRACT

Somatostatin type 2 receptor (SSTR2) radionuclide therapy using ß- particle-emitting radioligands has entered clinical practice for the treatment of neuroendocrine neoplasms (NENs). Despite the initial success of [177Lu]Lu­DOTA-TATE, theranostic SSTR2 radioligands require improved pharmacokinetics and enhanced compatibility with alternative radionuclides. Consequently, this study evaluates the pharmacokinetic effects of the albumin-binding domain cLAB4 on theranostic performance of copper­67-labeled NODAGA-TATE variants in an SSTR2-positive mouse pheochromocytoma (MPC) model. Methods: Binding, uptake, and release of radioligands as well as growth-inhibiting effects were characterized in cells grown as monolayers and spheroids. Tissue pharmacokinetics, absorbed tumor doses, and projected human organ doses were determined from quantitative SPECT imaging in a subcutaneous tumor allograft mouse model. Treatment effects on tumor growth, leukocyte numbers, and renal albumin excretion were assessed. Results: Both copper­64- and copper­67-labeled versions of NODAGA-TATE and NODAGA-cLAB4­TATE showed similar SSTR2 binding affinity, but faster release from tumor cells compared to the clinical reference [177Lu]Lu­DOTA-TATE. The bifunctional SSTR2/albumin-binding radioligand [67Cu]Cu­NODAGA-cLAB4­TATE showed both an improved uptake and prolonged residence time in tumors resulting in equivalent treatment efficacy to [177Lu]Lu­DOTA-TATE. Absorbed doses were well tolerated in terms of leukocyte counts and kidney function. Conclusion: This preclinical study demonstrates therapeutic efficacy of [67Cu]Cu­NODAGA-cLAB4­TATE in SSTR2-positive tumors. As an intrinsic radionuclide theranostic agent, the radioligand provides stable radiocopper complexes and high sensitivity in SPECT imaging for prospective determination and monitoring of therapeutic doses in vivo. Beyond that, copper­64- and copper­61-labeled versions offer possibilities for pre- and post-therapeutic PET. Therefore, NODAGA-cLAB4-TATE has the potential to advance clinical use of radiocopper in SSTR2-targeted cancer theranostics.


Subject(s)
Copper Radioisotopes , Heterocyclic Compounds, 1-Ring , Radiopharmaceuticals , Receptors, Somatostatin , Animals , Receptors, Somatostatin/metabolism , Mice , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/pharmacology , Radiopharmaceuticals/therapeutic use , Humans , Albumins , Cell Line, Tumor , Pheochromocytoma/radiotherapy , Pheochromocytoma/diagnostic imaging , Pheochromocytoma/metabolism , Acetates/chemistry , Theranostic Nanomedicine/methods , Tissue Distribution , Female , Disease Models, Animal
11.
Heliyon ; 10(18): e36445, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39315182

ABSTRACT

Objectives: To comprehensively analyze the copper metabolism in Breast cancer, we established a prognostic signature for breast cancer (BC) related to copper metabolism. Methods: Copper metabolism-related genes were sourced from previous literatures and were selected by the Univariate Cox regression. Cu-enrichment scores were calculated via ssGSEA. Differentially expressed genes were identified with limma between high and low Cu-enrichment scores group, then we used the Random Survival Forest and LASSO to build the CuScore for BC. Kaplan-Meier analysis, ROC curves, and Cox regression were used to evaluate CuScore. Genomic mutations were analyzed with GISTIC. Immune cells were examined using ESTIMATE, ssGSEA and TIMER. Enrichment analysis used clusterProfiler and GSVA. The GDSC database and oncoPredict package analyzed chemotherapeutic sensitivity. MMP13 was selected for in vitro assays. Results: Four copper metabolism-related genes (UBE2D2, SLC31A1, ATP7A, and MAPK1) with prognostic value were identified. Higher expression levels of these genes were associated with higher Cu-enrichment scores, a factor of malignancy in breast cancer. Among 115 differentially expressed genes, 19 prognostic genes were identified, with three (CEACAM5, MMP13, and CRISP3) highlighted by Random Survival Forest and LASSO. Higher CuScores correlated with worse prognoses and were effective in predicting breast cancer outcomes. CuScore and metastasis were independent prognostic factors. Tumor-infiltrating immune cells were associated with lower CuScores. GO-GSEA analysis indicated six immune-related pathways might be regulated by CuScore. Patients with higher CuScores had lower TMB and were more sensitive to Sapitinib and LCL161, while those with lower CuScores might respond better to anti-PD1 therapy. High MMP13 expression in breast cancer was linked to malignancy, affecting cell proliferation and migration. Conclusion: The identified copper metabolism-related gene signature has the potential to predict prognosis and guide clinical treatment for BC. Among these genes, MMP13 may act as a malignant factor in BC.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125154, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39316859

ABSTRACT

Tracing copper ions levels in the environment and subcellular microenvironment is crucial due to the key role copper ions play in physiological and pathological processes. Herein, a novel naphthalimide-fused rhodamine probe Rh-Naph-Cu was prepared through modification with phenylhydrazine to produce a closed and non-fluorescent spirolactam. Based on the copper-induced spirolactam ring-opening and hydrolysis process, Rh-Naph-Cu can be employed as a fluorescence off-on probe for copper ions with high selectivity, high sensitivity (limit of detection: 33.0 nM), broad pH-response range (pH: 5.0-10.0), and color change visible with the naked eye. Rh-Nap-Cu could be made into test strips for the in-situ chromogenic detection of Cu2+. Significantly, Rh-Naph-Cu can be utilized for the detection of copper ions in living HeLa cells and zebrafish, and exhibits excellent lysosomal-targeting ability with high Pearson's correlation coefficient (PCC) of 0.96.

13.
Angew Chem Int Ed Engl ; : e202415792, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39317646

ABSTRACT

This integrated computational and experimental study comprehensively examines the viability of competing inner-sphere electron transfer (ISET) and outer-sphere electron transfer (OSET) processes in [Cu(dap)2]+-mediated atom-transfer radical additions (ATRA) of olefins and CF3SO2Cl that can deliver both R-SO2Cl and R-Cl products. Five sterically- and electronically-varied representative alkenes were selected from which to explore and reconcile the range of experimentally observed outcomes. Findings are consistent with photoexcited [Cu(dap)2]+ initiating photoelectron transfer via ISET and the subsequent regeneration of the oxidized catalyst via single-electron transfer in the ground state via ISET to close the catalytic cycle and liberate products. R-SO2Cl/R-Cl product ratios appear to be primarily governed by the relative rates of direct catalyst regeneration {i.e., [Cu(dap)2SO2Cl]•+ + R•} and ligand exchange {i.e., [Cu(dap)2SO2Cl]•+ + Cl- }. Through this work, a more consistent and more complete conceptual framework has been developed to better understand this chemistry and how catalyst regeneration occurs. It is this important ground state process, which closes the catalytic cycle, and ultimately controls the enantioselectivity of ATRA reactions employing chiral copper photocatalysts.

14.
Avian Pathol ; : 1-33, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39319416

ABSTRACT

ABSTRACTThe use of copper nanoparticles (CuNP) in the diet of broiler chickens has been studied as a potential alternative to antibiotic growth promoters. This study aimed to analyze the antimicrobial properties of CuNP in the feed and water of broiler chickens against Salmonella Enteritidis and to assess the intestinal integrity and toxicity of CuNP supplementation in their diet. The antimicrobial activity of CuNP against S. Enteritidis was tested in microplates to evaluate three water samples with different mineral compositions and in an in vitro digestibility model that simulated the three primary intestinal compartments of birds to assess feed samples. To evaluate in vivo intestinal integrity and toxicity, the birds were divided into four groups (30 birds per group): (1) basal diet (control); (2) basal diet + CuNP (100 ppm); (3) basal diet + enramycin (10 ppm); and (4) basal diet + CuNP (100 ppm) + enramycin (10 ppm). Intestinal samples were collected for histomorphometric evaluation and lactic acid bacteria count, while chest muscle and whole blood samples were collected to determine copper content. A significant reduction in the S. Enteritidis count was observed in both in vitro treatments (water and feed) with CuNP inclusion, compared to the control group. No significant differences histomorphometric measurements, weight gain, or total lactic acid bacterial counts were found compared to those in the control. These results demonstrate the effectiveness of CuNP in reducing the occurrence of S. Enteritidis and their non-interference with the intestinal integrity of broiler chickens, highlighting the potential of CuNP as an alternative antimicrobial agent in the poultry production chain.

15.
Antioxidants (Basel) ; 13(9)2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39334807

ABSTRACT

A series of edaravone derivatives and the corresponding Cu(II) complexes were synthesized and characterized using spectroscopic and analytical techniques such as IR, UV, NMR and elemental analysis. Antioxidant activities of all compounds were examined using free radical scavenging methods such as hydrogen peroxide scavenging activity (HPSA), 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays. All of the tested compounds exhibited good antioxidant activity. Further, the frontier orbital energy levels, as well as various chemical properties, were determined using the density functional theory (DFT) calculations. The MEP maps of all of the derivatives were plotted to identify the nucleophilic and electrophilic reactive sites. Further, binding energies of all of the organic compounds with the protein tyrosinase was investigated to determine their potential anti-melanogenic applications. The selected ligand, L6 was subjected to molecular dynamics simulation analysis to determine the stability of the ligand-protein complex. The MD simulation was performed (150 ns) to estimate the stability of the tyrosinase-L6 complex. Other key parameters, such as, RMSD, RMSF, Rg, hydrogen bonds, SASA and MMPBSA were also analyzed to understand the interaction of L6 with the tyrosinase protein.

16.
Biomolecules ; 14(9)2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39334869

ABSTRACT

A low level of Neurotrophins (NTs), their Tyrosine Kinase Receptors (Trks), Vascular Endothelial Growth Factors (VEGFs) and their receptors, mainly VEGFR1 and VEGFR2, characterizes AD brains. The use of NTs and VEGFs as drugs presents different issues due to their low permeability of the blood-brain barrier, the poor pharmacokinetic profile, and the relevant side effects. To overcome these issues, different functional and structural NT mimics have been employed. Being aware that the N-terminus domain as the key domain of NTs for the binding selectivity and activation of Trks and the need to avoid or delay proteolysis, we herein report on the mimicking ability of two cyclic peptide encompassing the N-terminus of Brain Derived Growth Factor (BDNF), (c-[HSDPARRGELSV-]), cBDNF(1-12) and of Neurotrophin3 (NT3), (c-[YAEHKSHRGEYSV-]), cNT3(1-13). The two cyclic peptide features were characterized by a combined thermodynamic and spectroscopic approach (potentiometry, NMR, UV-vis and CD) that was extended to their copper(II) ion complexes. SH-SY5Y cell assays show that the Cu2+ present at the sub-micromolar level in the complete culture media affects the treatments with the two peptides. cBDNF(1-12) and cNT3(1-13) act as ionophores, induce neuronal differentiation and promote Trks and CREB phosphorylation in a copper dependent manner. Consistently, both peptide and Cu2+ stimulate BDNF and VEGF expression as well as VEGF release; cBDNF(1-12) and cNT3(1-13) induce the expression of Trks and VEGFRs.


Subject(s)
Brain-Derived Neurotrophic Factor , Brain , Copper , Neurotrophin 3 , Signal Transduction , Humans , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/chemistry , Neurotrophin 3/metabolism , Neurotrophin 3/chemistry , Copper/metabolism , Copper/chemistry , Signal Transduction/drug effects , Brain/metabolism , Brain/drug effects , Peptides, Cyclic/pharmacology , Peptides, Cyclic/chemistry , Peptides, Cyclic/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Cell Line, Tumor
17.
Antibiotics (Basel) ; 13(9)2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39335085

ABSTRACT

Background: The ascomycete Botrytis cinerea is a major pathogen of strawberry, often causing grey mold and significant yield losses. Its management has largely relied on chemical fungicides, which, while effective, can lead to resistant pathogens and harm to non-target organisms and pose health risks. Objectives: This study explored a strategy for minimizing chemical usage by combining biocontrol agents (BCAs) with half-strength fungicide input. Results: In vitro results of fungicide-amended culture plates indicated that the presence of 625 µg mL-1 Azoxystrobin exhibited no growth inhibition of T. atroviride T19 and T. harzianum T16 but increased conidial density of T16 by 90%. Copper (750 µg mL-1) did not suppress the growth of T. virens TVSC or T16 but rather promoted it by 9.5% and 6%, respectively. Additionally, copper increased T16 sporulation by 1.4-fold. Greenhouse trials demonstrated that combining T23 with half-strength Azoxystrobin was as effective as the full dosage in suppressing flower rot. Among the antagonists assessed, Kosakonia sp. exhibited the lowest incidence of fruit rot, whereas T23 resulted in a moderate incidence. Moreover, the combination of T16 or Kosakonia sp. with half-strength copper was almost as effective as the full dosage in reducing fruit rot. Conclusions: Our findings suggest integrating these BCAs in the sustainable management of grey mold in strawberries.

18.
Materials (Basel) ; 17(18)2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39336185

ABSTRACT

The paper presents the results of studying the structure and phase state of tungsten and tungsten-copper alloy after pulsed action of compression plasma flows and irradiation with helium ions. The compression plasma flows were used to modify the surface layer of tungsten, as well as to create an alloy based on tungsten and copper. Using scanning electron microscopy and X-ray structural analysis, the formation of radiation defects on the tungsten surface was detected in the form of local areas of exfoliation and destruction, which begin to form at helium ion irradiation doses of 2 × 1017 cm-2. It is shown that preliminary plasma treatment of the surface in the melting mode leads to the complete disappearance of surface radiation defects up to a dose of 2 × 1017 cm-2, which may be associated with the formation of a fine-crystalline grain structure, the intergranular boundaries of which serve as effective sinks for primary radiation defects.

19.
Materials (Basel) ; 17(18)2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39336404

ABSTRACT

This comprehensive study explores the kinetics of adsorption and its photocatalytic degradation of methyl orange (MO) using an advanced copper-decorated photocatalyst in the form of hollow fibers (HFs). Designed to boost both adsorption capacity and photocatalytic activity, the photocatalyst was tested in batch experiments to efficiently remove MO from aqueous solutions. Various isotherm models, including Langmuir, Freundlich, Sips, Temkin, and Dubinin-Radushkevich, along with kinetic models like pseudo-first and pseudo-second order, Elovich, Bangham, and Weber-Morris, were utilized to assess adsorption capacity and kinetics at varying initial concentrations. The results indicated a favorable MO physisorption on the nanocomposite photocatalyst under specific conditions. Further analysis of photocatalytic degradation under UV exposure revealed that the material maintained high degradation efficiency and stability across different MO concentrations. Through the facilitation of reactive oxygen species generation, oxygen played a crucial role in enhancing photocatalytic performance, while the degradation process following the Langmuir-Hinshelwood model. The study also confirmed the robustness and sustained activity of the nanocomposite photocatalyst, which could be regenerated and reused over five successive cycles, maintaining 92% of their initial performance at concentrations up to 15 mg/L. Overall, this effective nanocomposite photocatalyst structured in the form of HF shows great promise for effectively removing organic pollutants through combined adsorption and photocatalysis, offering valuable potential in wastewater treatment and environmental remediation.

20.
Medicina (Kaunas) ; 60(9)2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39336525

ABSTRACT

Copper is an essential element in the diet of mammals, including humans. It plays an important role in the physiological regulation of various enzymes and is consequently involved in several biological processes such as angiogenesis, oxidative stress regulation, neuromodulation, and erythropoiesis. Copper is essential for facilitating the transfer of iron from cells to the bloodstream, which is necessary for proper absorption of dietary iron and the distribution of iron throughout the body. In particular, patients with end-stage renal failure who require renal replacement therapy are at increased risk for disorders of copper metabolism. Many studies on hemodialysis, peritoneal dialysis, and kidney transplant patients have focused on serum copper levels. Some reported mild deficiency, while others reported elevated levels or even toxicity. In some cases, it has been reported that alterations in copper metabolism lead to an increased risk of cardiovascular disease, malnutrition, anemia, or mielopathy. The aim of this review is to evaluate the role of copper in patients undergoing hemodialysis and its potential clinical implications.


Subject(s)
Copper , Kidney Failure, Chronic , Renal Dialysis , Humans , Copper/blood , Renal Dialysis/adverse effects , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications
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