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1.
Funct Plant Biol ; 512024 05.
Article in English | MEDLINE | ID: mdl-38753957

ABSTRACT

Detrimental effects of salinity could be mitigated by exogenous zinc (Zn) application; however, the mechanisms underlying this amelioration are poorly understood. This study demonstrated the interaction between Zn and salinity by measuring plant biomass, photosynthetic performance, ion concentrations, ROS accumulation, antioxidant activity and electrophysiological parameters in barley (Hordeum vulgare L.). Salinity stress (200mM NaCl for 3weeks) resulted in a massive reduction in plant biomass; however, both fresh and dry weight of shoots were increased by ~30% with adequate Zn supply. Zinc supplementation also maintained K+ and Na+ homeostasis and prevented H2 O2 toxicity under salinity stress. Furthermore, exposure to 10mM H2 O2 resulted in massive K+ efflux from root epidermal cells in both the elongation and mature root zones, and pre-treating roots with Zn reduced ROS-induced K+ efflux from the roots by 3-4-fold. Similar results were observed for Ca2+ . The observed effects may be causally related to more efficient regulation of cation-permeable non-selective channels involved in the transport and sequestration of Na+ , K+ and Ca2+ in various cellular compartments and tissues. This study provides valuable insights into Zn protective functions in plants and encourages the use of Zn fertilisers in barley crops grown on salt-affected soils.


Subject(s)
Homeostasis , Hordeum , Plant Roots , Potassium , Salinity , Zinc , Hordeum/drug effects , Hordeum/growth & development , Hordeum/metabolism , Plant Roots/drug effects , Plant Roots/growth & development , Plant Roots/metabolism , Zinc/pharmacology , Zinc/metabolism , Homeostasis/drug effects , Potassium/metabolism , Reactive Oxygen Species/metabolism , Sodium/metabolism , Salt Stress/drug effects , Photosynthesis/drug effects , Hydrogen Peroxide/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism
2.
ACS Appl Mater Interfaces ; 16(19): 24274-24294, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38699930

ABSTRACT

In the field of bone tissue engineering, recently developed Zn alloy scaffolds are considered potential candidates for biodegradable implants for bone regeneration and defect reconstruction. However, the clinical success of these alloys is limited due to their insufficient surface bioactivities. Further, the higher concentration of Zn2+ produced during degradation promotes antibacterial activity, but deteriorates osteogenic properties. This study fabricated an Azadirachta indica (neem)-assisted brushite-hydroxyapatite (HAp) coating on the recently developed Zn-2Cu-0.5Mg alloy to tackle the above dilemma. The microstructure, degradation behavior, antibacterial activity, and hemocompatibility, along with in vitro and in vivo cytocompatibility of the coated alloys, are systematically investigated. Microstructural analysis reveals flower-like morphology with uniformly grown flakes for neem-assisted deposition. The neem-assisted deposition significantly improves the adhesion strength from 12.7 to 18.8 MPa, enhancing the mechanical integrity. The potentiodynamic polarization study shows that the neem-assisted deposition decreases the degradation rate, with the lowest degradation rate of 0.027 mm/yr for the ZHN2 sample. In addition, the biomineralization process shows the apatite formation on the deposited coating after 21 days of immersion. In vitro cytotoxicity assay exhibits the maximum cell viability of 117% for neem-assisted coated alloy in 30% extract after 5d and the improved cytocompatibility which is due to the controlled release of Zn2+ ions. Meanwhile, neem-assisted coated alloy increases the ZOI by 32 and 24% for Gram-positive and Gram-negative bacteria, respectively. Acceptable hemolysis (<5%) and anticoagulation parameters demonstrate a promising hemocompatibility of the coated alloy. In vivo implantation illustrates a slight inflammatory response and vascularization after 2 weeks of subcutaneous implantation, and neo-bone formation in the defect areas of the rat femur. Micro-CT and histology studies demonstrate better osseointegration with satisfactory biosafety response for the neem-assisted coated alloy as compared to that without neem-assisted deposition. Hence, this neem-assisted brushite-Hap coating strategy elucidates a new perspective on the surface modification of biodegradable implants for the treatment of bone defects.


Subject(s)
Alloys , Calcium Phosphates , Coated Materials, Biocompatible , Zinc , Alloys/chemistry , Alloys/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Calcium Phosphates/chemistry , Calcium Phosphates/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Humans , Durapatite/chemistry , Durapatite/pharmacology , Materials Testing , Mice , Green Chemistry Technology , Absorbable Implants
3.
ACS Appl Mater Interfaces ; 16(22): 28041-28055, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38767982

ABSTRACT

Bacterial infection poses a significant challenge to wound healing and skin regeneration, leading to substantial economic burdens on patients and society. Therefore, it is crucial to promptly explore and develop effective methodologies for bacterial infections. Herein, we propose a novel approach for synthesizing nanostructures based on antisense oligonucleotides (ASOs) through the coordination-driven self-assembly of Zn2+ with ASO molecules. This approach aims to provide effective synergistic therapy for chronic wound infections caused by Staphylococcus aureus (S. aureus). The resulting hybrid nanoparticles successfully preserve the structural integrity and biological functionalities of ASOs, demonstrating excellent ASO encapsulation efficiency and bioaccessibility. In vitro antibacterial experiments reveal that Zn-ASO NPs exhibit antimicrobial properties against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. This antibacterial ability is attributed to the high concentration of metal zinc ions and the generation of high levels of reactive oxygen species. Additionally, the ftsZ-ASO effectively inhibits the expression of the ftsZ gene, further enhancing the antimicrobial effect. In vivo antibacterial assays demonstrate that the Zn-ASO NPs promote optimal skin wound healing and exhibit favorable biocompatibility against S. aureus infections, resulting in a residual infected area of less than 8%. This combined antibacterial strategy, which integrates antisense gene therapy and metal-coordination-directed self-assembly, not only achieves synergistic and augmented antibacterial outcomes but also expands the horizons of ASO coordination chemistry. Moreover, it addresses the gap in the antimicrobial application of metal-coordination ASO self-assembly, thereby advancing the field of ASO-based therapeutic approaches.


Subject(s)
Anti-Bacterial Agents , Oligonucleotides, Antisense , Staphylococcus aureus , Zinc , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Zinc/chemistry , Zinc/pharmacology , Oligonucleotides, Antisense/chemistry , Oligonucleotides, Antisense/pharmacology , Animals , Mice , Escherichia coli/drug effects , Microbial Sensitivity Tests , Staphylococcal Infections/drug therapy , Bacillus subtilis/drug effects , Humans , Wound Healing/drug effects
4.
Plant Physiol Biochem ; 211: 108693, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38714130

ABSTRACT

Abiotic stresses like salinity and micronutrient deficiency majorly affect wheat productivity. Applying mesoporous silica nanoparticles (MSiNPs) as a smart micronutrient delivery system can facilitate better stress management and nutrient delivery. In this purview, we investigated the potential of MSiNPs and Zn-loaded MSiNPs (Zn-MSiNPs) on the growth and physiology of wheat seedlings exposed to salinity stress (200 mM NaCl). Initially, the FESEM, DLS, and BET analysis portrayed nanoparticles' spherical shape, nano-size, and negatively charged mesoporous surface. A sustained release of Zn+2 from Zn-MSiNPs at 30 °C, diffused light, and pH 7 was perceived with a 96.57% release after 10 days. Further, the mitigation of NaCl stress in the wheat seedlings was evaluated with two different concentrations, each of MSiNPs and Zn-MSiNPs (1 g/L and 5 g/L), respectively. A meticulous improvement in the germination and growth of wheat seedlings was observed when treated with both MSiNPs and Zn-MSiNPs. A considerable increase in chlorophyll, total protein, and sugar content was in consort with a substantial decline in MDA, electrolyte leakage, and ROS accumulation, showcasing the nanomaterials' palliating effects. Most importantly, the K+/Na+ ratio in shoots increased significantly by 3.43 and 4.37 folds after being treated with 5 g/L Zn-MSiNPs, compared to their respective control sets (0 and 200 mM NaCl). Therefore, it can be concluded that the Zn-MSiNPs can effectively restrain the effects of salinity stress on wheat seedlings.


Subject(s)
Nanoparticles , Reactive Oxygen Species , Seedlings , Silicon Dioxide , Triticum , Zinc , Triticum/drug effects , Triticum/metabolism , Triticum/growth & development , Silicon Dioxide/chemistry , Seedlings/drug effects , Seedlings/metabolism , Seedlings/growth & development , Zinc/metabolism , Zinc/pharmacology , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Salt Stress/drug effects , Porosity , Osmosis/drug effects
5.
Int J Nanomedicine ; 19: 4163-4180, 2024.
Article in English | MEDLINE | ID: mdl-38751660

ABSTRACT

Purpose: The study aimed to address the non-specific toxicity of cytotoxins (CTX) in liver cancer treatment and explore their combined application with the photosensitizer Ce6, co-loaded into carbonized Zn/Co bimetallic organic frameworks. The goal was to achieve controlled CTX release and synergistic photodynamic therapy, with a focus on evaluating anti-tumor activity against human liver cancer cell lines (Hep G2). Methods: Purified cobra cytotoxin (CTX) and photosensitizer Ce6 were co-loaded into carbonized Zn/Co bimetallic organic frameworks, resulting in RGD-PDA@C-ZIF@(CTX+Ce6). The formulation was designed with surface-functionalization using polydopamine and tumor-penetrating peptide RGD. This approach aimed to facilitate controlled CTX release and enhance the synergistic effect of photodynamic therapy. The accumulation of RGD-PDA@C-ZIF@(CTX+Ce6) at tumor sites was achieved through RGD's active targeting and the enhanced permeability and retention (EPR) effect. In the acidic tumor microenvironment, the porous structure of the metal-organic framework disintegrated, releasing CTX and Ce6 into tumor cells. Results: Experiments demonstrated that RGD-PDA@C-ZIF@(CTX+Ce6) nanoparticles, combined with near-infrared laser irradiation, exhibited optimal anti-tumor effects against human liver cancer cells. The formulation showcased heightened anti-tumor activity without discernible systemic toxicity. Conclusion: The study underscores the potential of utilizing metal-organic frameworks as an efficient nanoplatform for co-loading cytotoxins and photodynamic therapy in liver cancer treatment. The developed formulation, RGD-PDA@C-ZIF@(CTX+Ce6), offers a promising avenue for advancing the clinical application of cytotoxins in oncology, providing a solid theoretical foundation for future research and development.


Subject(s)
Indoles , Liver Neoplasms , Metal-Organic Frameworks , Photochemotherapy , Photosensitizing Agents , Zinc , Humans , Photochemotherapy/methods , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Liver Neoplasms/drug therapy , Zinc/chemistry , Zinc/pharmacology , Indoles/chemistry , Indoles/pharmacology , Indoles/administration & dosage , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/administration & dosage , Animals , Hep G2 Cells , Cobalt/chemistry , Cobalt/pharmacology , Oligopeptides/chemistry , Oligopeptides/pharmacology , Oligopeptides/pharmacokinetics , Polymers/chemistry , Mice , Cytotoxins/chemistry , Cytotoxins/pharmacology , Cytotoxins/pharmacokinetics , Mice, Nude , Mice, Inbred BALB C , Cell Survival/drug effects
6.
ACS Appl Bio Mater ; 7(5): 3316-3329, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38691017

ABSTRACT

Basic fibroblast growth factor (bFGF) plays an important role in active wound repair. However, the existing dosage forms in clinical applications are mainly sprays and freeze-dried powders, which are prone to inactivation and cannot achieve a controlled release. In this study, a bioactive wound dressing named bFGF-ATP-Zn/polycaprolactone (PCL) nanodressing with a "core-shell" structure was fabricated by emulsion electrospinning, enabling the sustained release of bFGF. Based on the coordination and electrostatic interactions among bFGF, ATP, and Zn2+, as well as their synergistic effect on promoting wound healing, a bFGF-ATP-Zn ternary combination system was prepared with higher cell proliferation activity and used as the water phase for emulsion electrospinning. The bFGF-ATP-Zn/PCL nanodressing demonstrated improved mechanical properties, sustained release of bFGF, cytocompatibility, and hemocompatibility. It increased the proliferation activity of human dermal fibroblasts (HDFs) and enhanced collagen secretion by 1.39 and 3.45 times, respectively, while reducing the hemolysis rate to 3.13%. The application of the bFGF-ATP-Zn/PCL nanodressing in mouse full-thickness skin defect repair showed its ability to accelerate wound healing and reduce wound scarring within 14 days. These results provide a research basis for the development and application of this bioactive wound dressing product.


Subject(s)
Adenosine Triphosphate , Biocompatible Materials , Cell Proliferation , Emulsions , Fibroblast Growth Factor 2 , Materials Testing , Wound Healing , Zinc , Wound Healing/drug effects , Emulsions/chemistry , Animals , Zinc/chemistry , Zinc/pharmacology , Humans , Fibroblast Growth Factor 2/chemistry , Fibroblast Growth Factor 2/pharmacology , Mice , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Proliferation/drug effects , Adenosine Triphosphate/metabolism , Particle Size , Fibroblasts/drug effects , Polyesters/chemistry , Polyesters/pharmacology , Bandages
7.
J Dent ; 145: 105033, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697505

ABSTRACT

OBJECTIVES: This study aimed to enhance gingival fibroblast function and to achieve antibacterial activity around the implant abutment by using a zinc (Zn)-containing bioactive glass (BG) coating. METHODS: 45S5 BG containing 0, 5, and 10 wt.% Zn were coated on zirconia disks. The release of silica and Zn ions in physiological saline and their antibacterial effects were measured. The effects of BG coatings on human gingival fibroblasts (hGFs) were assessed using cytotoxicity assays and by analyzing the gene expression of various genes related to antioxidant enzymes, wound healing, and fibrosis. RESULTS: BG coatings are capable of continuous degradation and simultaneous ion release. The antibacterial effect of BG coatings increased with the addition of Zn, while the cytotoxicity remained unchanged compared to the group without coatings. BG coating enhances the expression of angiogenesis genes, while the Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CONCLUSIONS: The antibacterial effect of BG improved with the increase in Zn concentration, without inducing cytotoxicity. BG coating enhances the expression of angiogenesis genes, and Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CLINICAL SIGNIFICANCE: Adding 10 wt% Zn to BG could enhance the environment around implant abutments by providing antibacterial, antioxidant, and anti-fibrotic effects, having potential for clinical use.


Subject(s)
Anti-Bacterial Agents , Ceramics , Dental Abutments , Fibroblasts , Gingiva , Glass , Surface Properties , Zinc , Zirconium , Zirconium/pharmacology , Zirconium/chemistry , Humans , Zinc/pharmacology , Fibroblasts/drug effects , Anti-Bacterial Agents/pharmacology , Gingiva/cytology , Gingiva/drug effects , Glass/chemistry , Ceramics/pharmacology , Ceramics/chemistry , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Antioxidants/pharmacology , Materials Testing , Collagen , Wound Healing/drug effects , Dental Materials/pharmacology , Dental Materials/chemistry , Cells, Cultured
8.
Bioorg Chem ; 147: 107422, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705106

ABSTRACT

Two acylhydrazone based zinc(II) complexes [Zn(HL)2Cl2(CH3OH)2] (Zn1) and [ZnL(AC)]2 (Zn2) were synthesized from 3-(1-(salicyloylhydrazono)ethyl) pyridine (HL). Single crystal X-ray structure analyses showed that complexes Zn1 and Zn2 have a zero-dimensional monomer or dimer structure. Antiproliferative activity studies revealed that Zn1 and Zn2 are both more effective against A549 cells than cisplatin. The results of the reactive oxygen species (ROS) generation assay on A549 cells showed that both Zn1 and Zn2 induced apoptosis through ROS accumulation. The apoptosis-inducing and cell cycle arrest effects of Zn1 and Zn2 on A549 cells indicated that the antitumor effect was achieved through apoptosis induction and inhibition of DNA synthesis by blocking the G0/G1 phase of the cell cycle. What's more, the results of wound-healing assay showed that Zn1 and Zn2 could inhibit the migration of A549 cells. Western blot analysis further demonstrated that Zn1 and Zn2 induced cell apoptosis through the mitochondrial pathway, in which process, the expression level of cytochrome C, cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 9 proteins increased while pro-caspase 3 and pro-caspase 9 expression decreased. In vivo anticancer evaluation demonstrated that both Zn1 and Zn2 complexes effectively inhibited tumor growth without causing significant toxicity in systemic organs.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Coordination Complexes , Drug Screening Assays, Antitumor , Hydrazones , Lung Neoplasms , Zinc , Animals , Mice , A549 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Proliferation/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Dose-Response Relationship, Drug , Hydrazones/chemistry , Hydrazones/pharmacology , Hydrazones/chemical synthesis , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Reactive Oxygen Species/metabolism , Structure-Activity Relationship , Zinc/chemistry , Zinc/pharmacology
9.
Nanotechnology ; 35(32)2024 May 24.
Article in English | MEDLINE | ID: mdl-38701766

ABSTRACT

One of the global challenges for living things is to provide pollution and harmful microbes-free environment. In this study, magnetically retrievable spinel-structured manganese zinc ferrite (Mn0.5Zn0.5Fe2O4) (MZF) was synthesized by a facile solvothermal method. Further, the MZF with different weight percentages (10 wt%, 50 wt%, and 80 wt%) were supported on reduced graphene oxide (rGO). The phase purity and morphology of MZF and MZF/rGO nanocomposite were confirmed by x-ray diffraction technique and scanning electron microscopy, respectively. The Fourier transform infrared spectroscopy, Raman, UV-visible spectroscopy, and thermogravimetric analyses of the as-synthesized nanocomposites were examined for the detection of various chemical groups, band gap, and thermal properties, respectively. The MZF/rGO nanocomposite exhibited significant antibacterial and antifungal activity againstEggerthella lenta, Enterococcus faecalis, Klebsiella pneumonia, Pseudomonas aeruginosa,andCandida albicanscompared to bare MZF and rGO. The high surface area of rGO plays a crucible role in antimicrobial analysis. Additionally, the antibacterial and antifungal activity is compared by synthesizing various metal ferrites such as MnFe2O4, ZnFe2O4, and Fe3O4. The 50 wt% MZF/rGO nanocomposite exhibits significantly high antibacterial activity. However, 10 wt% MZF/rGO nanocomposite shows good antifungal activity than Fe3O4, MnFe2O4, ZnFe2O4, MnZnFe2O4, 50 wt%, and 80 wt% MZF/rGO nanocomposites. These findings suggest that the prepared ferrite nanocomposites hold promise for microbial inhibition.


Subject(s)
Bacteria , Ferric Compounds , Fungi , Graphite , Nanocomposites , Graphite/chemistry , Graphite/pharmacology , Ferric Compounds/chemistry , Ferric Compounds/pharmacology , Nanocomposites/chemistry , Fungi/drug effects , Bacteria/drug effects , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Zinc/chemistry , Zinc/pharmacology , Aluminum Oxide , Magnesium Oxide
10.
Langmuir ; 40(21): 10992-11010, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38743441

ABSTRACT

The exploration of environmentally friendly, less toxic, sustained-release insecticide is increasing with the growing demand for food to meet the requirements of the expanding population. As a sustained-release carrier, the unique, environmentally friendly intelligent responsive hydrogel system is an important factor in improving the efficiency of insecticide utilization and accurate release. In this study, we developed a facile approach for incorporating the natural compound rosin (dehydroabietic acid, DA) and zinc ions (Zn2+) into a poly(N-isopropylacrylamide) (PNIPAM) hydrogel network to construct a controlled-release hydrogel carrier (DA-PNIPAM-Zn2+). Then, the model insecticide avermectin (AVM) was encapsulated in the carrier at a drug loading rate of 36.32% to form AVM@DA-PNIPAM-Zn2+. Surprisingly, the smart controlled carrier exhibited environmental responsiveness, strongly enhanced mechanical properties, self-healing ability, hydrophobicity, and photostability to ensure a balance between environmental friendliness and the precision of the drug release. The release experiments showed that the carboxyl and amide groups in the polymer chains alter the intermolecular forces within the hydrogel meshes and ingredient diffusion by changing temperatures (25 and 40 °C) and pH values (5.8, 7.4, and 8.5), leading to different release behaviors. The insecticidal activity of the AVM@DA-PNIPAM-Zn2+ against oriental armyworms was good, with an effective minimum toxicity toward aquatic animals. Therefore, AVM@DA-PNIPAM-Zn2+ is an effective drug delivery system against oriental armyworms. We anticipate that this ecofriendly, sustainable, smart-response carrier may broaden the utilization rosin and its possible applications in the agricultural sector.


Subject(s)
Drug Carriers , Hydrogels , Insecticides , Ivermectin , Resins, Plant , Ivermectin/analogs & derivatives , Ivermectin/chemistry , Ivermectin/pharmacology , Ivermectin/toxicity , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Hydrogen-Ion Concentration , Insecticides/chemistry , Insecticides/pharmacology , Resins, Plant/chemistry , Drug Carriers/chemistry , Temperature , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Drug Liberation , Moths/drug effects , Rosaceae/chemistry , Zinc/chemistry , Zinc/pharmacology , Acrylic Resins
11.
Int J Biol Macromol ; 269(Pt 1): 132047, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38702008

ABSTRACT

In our study, we developed a novel nanobiocomposite using graphene oxide (GO), casein (Cas), ZnAl layered double hydroxide (LDH), sodium alginate (Alg), and Fe3O4 magnetic nanoparticles. To synthesize the GO, we used a modified Hummer's method and then covalently functionalized its surface with Cas protein. The functionalized GO was combined with as-synthesized ZnAl LDH, and the composite was conjugated with alginate hydrogel through the gelation process. Finally, we magnetized the nanobiocomposite using in-situ magnetization. The nanobiocomposite was comprehensively characterized using FT-IR, FE-SEM, EDX, and XRD. Its biological potential was assessed through cell viability, hemolysis, and anti-biofilm assays, as well as its application in hyperthermia. The MTT assay showed high cell viability percentages for Hu02 cells after 24, 48, and 72 h of incubation. The nanobiocomposite had a hemolytic effect lower than 3.84 %, and the measured bacterial growth inhibition percentages of E. coli and S. aureus bacteria in the presence of the nanobiocomposite were 52.18 % and 55.72 %, respectively. At a concentration of 1 mg.mL-1 and a frequency of 400 kHz, the nanocomposite exhibits a remarkable specific absorption rate (SAR) of 67.04 W.g-1, showcasing its promising prospects in hyperthermia applications.


Subject(s)
Alginates , Caseins , Graphite , Hydrogels , Hydroxides , Magnetite Nanoparticles , Graphite/chemistry , Graphite/pharmacology , Alginates/chemistry , Caseins/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Hydroxides/chemistry , Magnetite Nanoparticles/chemistry , Humans , Nanocomposites/chemistry , Cell Survival/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Escherichia coli/growth & development , Hemolysis/drug effects , Staphylococcus aureus/drug effects , Zinc/chemistry , Zinc/pharmacology , Biofilms/drug effects
12.
Med Sci Monit ; 30: e942946, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38698627

ABSTRACT

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.


Subject(s)
Cryopreservation , Cryoprotective Agents , DNA Fragmentation , Membrane Potential, Mitochondrial , Reactive Oxygen Species , Semen Preservation , Sperm Motility , Spermatozoa , Zinc , Male , Cryopreservation/methods , Humans , Spermatozoa/drug effects , Spermatozoa/metabolism , Cryoprotective Agents/pharmacology , Reactive Oxygen Species/metabolism , Sperm Motility/drug effects , Semen Preservation/methods , Membrane Potential, Mitochondrial/drug effects , DNA Fragmentation/drug effects , Zinc/pharmacology , Zinc/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Semen Analysis , Cell Survival/drug effects , Adult , Mitochondria/drug effects , Mitochondria/metabolism , Acrosome/drug effects , Acrosome/metabolism , Freezing
13.
Dalton Trans ; 53(22): 9416-9432, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38758025

ABSTRACT

Zinc(II)-complexes with the general formula [Zn(L)2] containing 8-hydroxyquinoline Schiff bases functionalized with 1-(3-aminopropyl)imidazole or 1-(3-aminopropyl)-2-methyl-1H-imidazole on 2-position and their respective ligands (HL1 or HL2) were synthesized and characterized by NMR, UV-Vis, FTIR and CD spectroscopies as well as ESI-MS spectrometry. Single crystals of HL2 and [Zn(L1)2]n were analysed by SC-XRD. [Zn(L1)2]n shows a 1D polymeric chain structure of alternating Zn(II) cations and bridging Schiff base ligands, in contrast to previously reported monomeric structures of analogous complexes. DFT calculations were performed to rationalize the polymeric X-ray structure of Zn(L1)2. Results showed that the ligands can bind as bi- or tridentate to Zn(II) and there is the possibility of a dynamic behavior for the complexes in solution. Both ligands and complexes present limited stability in aqueous media, however, in the presence of bovine serum albumin the complexes are stable. Molecular docking simulations and circular dichroism spectroscopic studies suggest binding to this protein in close proximity to the Trp213 residue. Biological studies on a panel of cancer cells revealed that the Zn(II)-complexes have a lower impact on cell viability than cisplatin, except for triple-negative breast cancer cells in which they were comparable. Notwithstanding, they display much higher selectivity towards cancer cells vs. normal cells, than cisplatin. They induce the generation of ROS and DNA double-strand breaks, primarily through apoptosis as the mode of cell death. Overall, the novel Zn(II)-complexes demonstrate improved induction of apoptosis and higher selectivity, particularly for melanoma cells, compared to previously reported analogues, making them promising candidates for clinical application.


Subject(s)
Antineoplastic Agents , Coordination Complexes , Imidazoles , Schiff Bases , Zinc , Schiff Bases/chemistry , Schiff Bases/pharmacology , Zinc/chemistry , Zinc/pharmacology , Humans , Imidazoles/chemistry , Imidazoles/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis , Melanoma/pathology , Melanoma/drug therapy , Density Functional Theory , Apoptosis/drug effects , Molecular Docking Simulation , Cell Line, Tumor , Cell Survival/drug effects , Cell Proliferation/drug effects , Molecular Structure , Drug Screening Assays, Antitumor , Serum Albumin, Bovine/chemistry
14.
Colloids Surf B Biointerfaces ; 239: 113927, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38714078

ABSTRACT

Humans often have bleeding, which exerts substantial selective pressure on the coagulation system to optimize hemostasis in a variety of situations. Uncontrolled hemorrhage due to severe trauma leads to morbidity and mortality. Although nonbiological surfaces such as silicates can activate coagulation factor XII (FXII), the presence of Zn (Zinc) in the material stimulates and activates the various steps in the coagulation cascade. This results in blood clotting. The Zn@SiO2 nanocomposite has an excellent hemostatic property that establishes hemostasis by activating the factors responsible for the formation of a stable clot called fibrin mesh. This can be used as a hemostatic agent during surgeries and in any other trauma condition related to bleeding. Zn@SiO2 was synthesized and characterized with XRD, FTIR and HRTEM. It is analyzed for its RBC (Red Blood Corpuscles) aggregation and Platelet adhesion ability, fibrin formation, thrombus formation and prothrombin time (PT), Activated Partial Thromboplastin Time (aPTT), D-dimer for its ability to activate the coagulation cascade to achieve stable clotting.


Subject(s)
Blood Coagulation , Nanocomposites , Silicon Dioxide , Zinc , Nanocomposites/chemistry , Blood Coagulation/drug effects , Zinc/chemistry , Zinc/pharmacology , Silicon Dioxide/chemistry , Humans , Partial Thromboplastin Time , Prothrombin Time , Platelet Adhesiveness/drug effects , Animals , Particle Size , Fibrin Fibrinogen Degradation Products/metabolism , Hemostatics/chemistry , Hemostatics/pharmacology
15.
Bioorg Med Chem Lett ; 108: 129810, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38782078

ABSTRACT

PCI-34051 is a valuable tool to interrogate the therapeutic effects of selective inhibition of HDAC8. However, it has not advanced to clinical trials, perhaps due to poor PK or off-target effects. We hypothesized that the presence of a hydroxamic acid (HA) group in PCI-34051 contributed to its lack of advancement. Therefore, we replaced the HA in the PCI-34051 scaffold with a series of moieties that have the potential to bind to Zn and evaluated their activity in a HDAC8 assay. Surprisingly, none of the replacements effectively mimicked the HA, and analogs lost significant potency. Evaluation of the analogs' affinity to Zn indicated that none had affinity for Zn within the same range as the HA. These studies point to the difficulty in the application of bioisosteric replacements for Zn binding motifs.


Subject(s)
Histone Deacetylase Inhibitors , Histone Deacetylases , Hydroxamic Acids , Repressor Proteins , Histone Deacetylases/metabolism , Hydroxamic Acids/chemistry , Hydroxamic Acids/pharmacology , Hydroxamic Acids/chemical synthesis , Histone Deacetylase Inhibitors/chemistry , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemical synthesis , Humans , Repressor Proteins/antagonists & inhibitors , Repressor Proteins/metabolism , Structure-Activity Relationship , Zinc/chemistry , Zinc/pharmacology , Molecular Structure , Sulfonamides/chemistry , Sulfonamides/pharmacology , Sulfonamides/chemical synthesis , Dose-Response Relationship, Drug , Indoles
16.
Colloids Surf B Biointerfaces ; 239: 113969, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749168

ABSTRACT

In this study, poly (lactic acid)/zinc-doped nano hydroxyapatite (PLA/nano-ZnHA) composite microspheres were prepared and formed into injectable bone paste with sodium alginate (SA) and polyvinyl alcohol (PVA) for bone defect repair. The effect of component of bone paste on injectability and zinc doping content related biological properties were mainly discussed. An injectable bone paste of PLA/nano-ZnHA composite microspheres (CM) was formed in mass ratio of (2.5-25):(0.25-4): (0-2.5):(20-65) of CM, SA, PVA and water with the favorable injectability (average force:4.46±1.72 N). In vitro 5%-10% zinc doping content displayed significantly higher promotion on cell proliferation and osteogenic differentiation than 15%-20% zinc doping content. Furthermore, in vivo the significant promoting effect of 0-5% zinc doping in ZnHA on bone repair was observed. Although 5% zinc doping content did not show a significant enhancement in bone volume/tissue volume (BV/TV), it has the ability to improve the bone mineral density (BMD) in early stage of bone repair compared with the 0% zinc doping content. The PLA/nano-ZnHA composite microsphere injectable paste with convenient surgical operation and well filling ability has the potential to become a competitive tissue repair material.


Subject(s)
Durapatite , Microspheres , Polyesters , Skull , Zinc , Polyesters/chemistry , Durapatite/chemistry , Durapatite/pharmacology , Zinc/chemistry , Zinc/pharmacology , Animals , Skull/drug effects , Skull/pathology , Cell Proliferation/drug effects , Osteogenesis/drug effects , Injections , Cell Differentiation/drug effects
17.
Colloids Surf B Biointerfaces ; 239: 113971, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38759296

ABSTRACT

The optimal material for repairing skull defects should exhibit outstanding biocompatibility and mechanical properties. Specifically, hydrogel scaffolds that emulate the microenvironment of the native bone extracellular matrix play a vital role in promoting osteoblast adhesion, proliferation, and differentiation, thereby yielding superior outcomes in skull reconstruction. In this study, a composite network hydrogel comprising sodium alginate (SA), epigallocatechin gallate (EGCG), and zinc ions (Zn2+) was developed to establish an ideal osteogenic microenvironment for bone regeneration. Initially, physical entanglement and hydrogen bonding between SA and EGCG resulted in the formation of a primary network hydrogel known as SA-EGCG. Subsequently, the inclusion of Zn2+ facilitated the creation of a composite network hydrogels named SA-EGCG-Zn2+ via dynamic coordination bonds with SA and EGCG. The engineered SA-EGCG2 %-Zn2+ hydrogels offered an environment mimicking the native extracellular matrix (ECM). Moreover, the sustained release of Zn2+ from the hydrogel effectively enhanced cell adhesion, promoted proliferation, and stimulated osteoblast differentiation. In vitro experiments have shown that SA-EGCG2 %-Zn2+ hydrogels greatly enhance the attachment and growth of osteoblast precursor cells (MC3T3-E1), while also increasing the expression of genes related to osteogenesis in these cells. Additionally, in vivo studies have confirmed that SA-EGCG2 %-Zn2+ hydrogels promote new bone formation and accelerate the regeneration of bone in situ, indicating promising applications in the realm of bone tissue engineering.


Subject(s)
Alginates , Catechin , Cell Proliferation , Hydrogels , Skull , Tissue Scaffolds , Zinc , Zinc/chemistry , Zinc/pharmacology , Alginates/chemistry , Alginates/pharmacology , Catechin/chemistry , Catechin/analogs & derivatives , Catechin/pharmacology , Skull/drug effects , Skull/injuries , Skull/pathology , Animals , Mice , Hydrogels/chemistry , Hydrogels/pharmacology , Tissue Scaffolds/chemistry , Cell Proliferation/drug effects , Osteoblasts/drug effects , Osteoblasts/cytology , Osteoblasts/metabolism , Cell Differentiation/drug effects , Osteogenesis/drug effects , Bone Regeneration/drug effects , Cell Adhesion/drug effects
18.
Pol Merkur Lekarski ; 52(2): 178-188, 2024.
Article in English | MEDLINE | ID: mdl-38642353

ABSTRACT

OBJECTIVE: Aim: To evaluate the cytotoxic activity of newly synthesized a series of novel HDAC inhibitors comprising sulfonamide as zinc binding group and Isatin derivatives as cap group joined by mono amide linker as required to act as HDAC inhibitors. PATIENTS AND METHODS: Materials and Methods: The utilization of sulfonamide as zinc binding group joined by N-alkylation reaction with ethyl-bromo hexanoate as linker group that joined by amide reaction with Isatin derivatives as cap groups which known to possess antitumor activity in the designed of new histone deacetylase inhibitors and using the docking and MTT assay to evaluate the compounds. RESULTS: Results: Four compounds have been synthesized and characterized successfully by ART-FTIR, NMR and ESI-Ms. the compounds were synthesized and characterized by successfully by ART-FTIR, NMR and ESI- Ms. Assessed for their cytotoxic activity against human colon adenocarcinoma MCF-7 (IC50, I=105.15, II=60.00, III=54.11, IV=56.57, vorinostat=28.41) and hepatoblastoma HepG2 (IC50, I=63.91, II=135.18, III=118.85, IV=51.46, vorinostat=37.50). Most of them exhibited potent HDAC inhibitory activity and significant cytotoxicity. CONCLUSION: Conclusions: The synthesized compounds (I, II, III and IV) showed cytotoxicity toward MCF-7 and HepG2 cancer cell lines and their docking analysis provided a preliminary indication that they are viable [HDAC6] candidates.


Subject(s)
Adenocarcinoma , Antineoplastic Agents , Colonic Neoplasms , Isatin , Humans , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Vorinostat/pharmacology , Isatin/pharmacology , Cell Line, Tumor , Amides/pharmacology , Drug Design , Antineoplastic Agents/pharmacology , Sulfonamides/pharmacology , Zinc/metabolism , Zinc/pharmacology , Cell Proliferation , Molecular Structure
19.
Int J Mol Sci ; 25(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38612821

ABSTRACT

Antibiotic resistance is currently a global health emergency. Metallodrugs, especially metal coordination complexes, comprise a broad variety of candidates to combat antibacterial infections. In this work, we designed a new family of Schiff base zinc(II) complexes with iminopyridine as an organic ligand and different inorganic ligands: chloride, nitrate, and acetate. The antibacterial effect of the Zn(II) complexes was studied against planktonic bacterial cells of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains. The results showed a moderate biocide activity in both types of planktonic bacteria, which arises from the metal complexation to the Schiff base ligand. Importantly, we confirmed the crucial effect of the metal, with Zn(II) improving the activity of Cu(II) counterparts previously reported. On the other hand, the impact of the inorganic ligands was not significant for the antibacterial effect but was relevant for the complex solubility. Finally, as proof of concept of topical antibacterial formulation, we formulated an emulsion containing the most lipophilic Zn(II) complex and confirmed a sustained release for 24 h in a vertical cell diffusion assay. The promising activity of iminopyridine Zn(II) complexes is potentially worth exploring in more detailed studies.


Subject(s)
Coordination Complexes , Zinc , Zinc/pharmacology , Ligands , Schiff Bases/pharmacology , Nitrates , Coordination Complexes/pharmacology , Anti-Bacterial Agents/pharmacology , Escherichia coli , Plankton
20.
Colloids Surf B Biointerfaces ; 238: 113880, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38581836

ABSTRACT

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.


Subject(s)
Alloys , Calcium , Magnesium , Zinc , Alloys/chemistry , Alloys/pharmacology , Corrosion , Animals , Zinc/chemistry , Zinc/pharmacology , Magnesium/chemistry , Mice , Calcium/chemistry , Calcium/metabolism , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Surface Properties , Materials Testing , Cell Proliferation/drug effects , Hydroxyapatites/chemistry , Cell Line , Durapatite/chemistry , Durapatite/pharmacology
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