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1.
Med Sci Monit ; 30: e942946, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698627

RESUMO

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.


Assuntos
Criopreservação , Crioprotetores , Fragmentação do DNA , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Zinco , Masculino , Criopreservação/métodos , Humanos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Crioprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Preservação do Sêmen/métodos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Zinco/farmacologia , Zinco/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Análise do Sêmen , Sobrevivência Celular/efeitos dos fármacos , Adulto , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Acrossomo/efeitos dos fármacos , Acrossomo/metabolismo , Congelamento
2.
ACS Biomater Sci Eng ; 10(5): 3438-3453, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38564666

RESUMO

Despite being a weaker metal, zinc has become an increasingly popular candidate for biodegradable implant applications due to its suitable corrosion rate and biocompatibility. Previous studies have experimented with various alloy elements to improve the overall mechanical performance of pure Zn without compromising the corrosion performance and biocompatibility; however, the thermal stability of biodegradable Zn alloys has not been widely studied. In this study, TiC nanoparticles were introduced for the first time to a Zn-Al-Cu system. After hot rolling, TiC nanoparticles were uniformly distributed in the Zn matrix and effectively enabled phase control during solidification. The Zn-Cu phase, which was elongated and sharp in the reference alloy, became globular in the nanocomposite. The strength of the alloy, after introducing TiC nanoparticles, increased by 31% from 259.7 to 340.3 MPa, while its ductility remained high at 49.2% elongation to failure. Fatigue performance also improved greatly by adding TiC nanoparticles, increasing the fatigue limit by 47.6% from 44.7 to 66 MPa. Furthermore, TiC nanoparticles displayed excellent phase control capability during body-temperature aging. Without TiC restriction, Zn-Cu phases evolved into dendritic morphologies, and the Al-rich eutectic grew thicker at grain boundaries. However, both Zn-Cu and Al-rich eutectic phases remained relatively unchanged in shape and size in the nanocomposite. A combination of exceptional tensile properties, improved fatigue performance, better long-term stability with a suitable corrosion rate, and excellent biocompatibility makes this new Zn-Al-Cu-TiC material a promising candidate for biodegradable stents and other biodegradable applications.


Assuntos
Implantes Absorvíveis , Cobre , Stents , Zinco , Zinco/química , Zinco/farmacologia , Cobre/química , Cobre/farmacologia , Ligas/química , Humanos , Titânio/química , Titânio/farmacologia , Alumínio/química , Alumínio/farmacologia , Teste de Materiais , Corrosão , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Nanopartículas/química , Nanocompostos/química
3.
ACS Biomater Sci Eng ; 10(5): 2967-2982, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38632925

RESUMO

In recent years, nanomaterials have gained widespread use in the biomedical field, with ZIF-8 and ZnO emerging as promising candidates due to their remarkable performance in osteogenesis, angiogenesis, and antimicrobial therapy. However, before advancing these nanomaterials for clinical applications, it is imperative to evaluate their biocompatibility. In particular, comparing nanomaterials with similar biomedical functions is crucial for identifying the most suitable nanomaterials for further development and market entry. Our study aimed to compare the biocompatibility of nano-ZIF-8 and nano-ZnO under the same conditions. We found that nano-ZIF-8 exhibited lower toxicity both in vitro and in vivo compared to nano-ZnO. To gain insights into the underlying mechanisms responsible for this difference, we conducted further experiments to investigate lysosome damage, mitochondrial change, and the occurrence of ferroptosis. Additionally, we performed transcriptome sequencing to analyze the expression of relevant genes, thereby providing robust validation for our findings. In summary, our study highlighted the importance of evaluating nanomaterials with similar biomedical effects. Through this comparative study, we have not only shed light on the superior biocompatibility of nano-ZIF-8 over nano-ZnO, but also contributed valuable insights and methodological references for future material screening endeavors. Ultimately, our study served as a stepping stone toward the development of safer and more effective nanomaterials for various biomedical applications.


Assuntos
Materiais Biocompatíveis , Óxido de Zinco , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Animais , Camundongos , Humanos , Zinco/química , Zinco/farmacologia , Ferroptose/efeitos dos fármacos , Teste de Materiais , Nanoestruturas/química , Nanoestruturas/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Zeolitas/química , Zeolitas/farmacologia
4.
J Colloid Interface Sci ; 668: 88-97, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38669999

RESUMO

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.


Assuntos
Doxorrubicina , Peróxido de Hidrogênio , Oxigênio , Fotoquimioterapia , Nanomedicina Teranóstica , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Animais , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Oxigênio/química , Oxigênio/metabolismo , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Tamanho da Partícula , Propriedades de Superfície , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Peróxidos/química , Peróxidos/farmacologia , Nanopartículas/química , Camundongos Endogâmicos BALB C , Zinco/química , Zinco/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem
5.
Colloids Surf B Biointerfaces ; 238: 113880, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581836

RESUMO

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.


Assuntos
Ligas , Cálcio , Magnésio , Zinco , Ligas/química , Ligas/farmacologia , Corrosão , Animais , Zinco/química , Zinco/farmacologia , Magnésio/química , Camundongos , Cálcio/química , Cálcio/metabolismo , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Propriedades de Superfície , Teste de Materiais , Proliferação de Células/efeitos dos fármacos , Hidroxiapatitas/química , Linhagem Celular , Durapatita/química , Durapatita/farmacologia
6.
Int J Biol Macromol ; 267(Pt 2): 131477, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604430

RESUMO

Salt stress severely limits the growth and yield of wheat in saline-alkali soil. While nanozymes have shown promise in mitigating abiotic stress by scavenging reactive oxygen species (ROS) in plants, their application in alleviating salt stress for wheat is still limited. This study synthesized a highly active nanozyme catalyst known as ZnPB (Zn-modified Prussian blue) to improve the yield and quality of wheat in saline soil. According to the Michaelis-Menten equation, ZnPB demonstrates exceptional peroxidase-like enzymatic activity, thereby mitigating oxidative damage caused by salt stress. Additionally, studies have shown that the ZnPB nanozyme is capable of regulating intracellular Na+ efflux and K+ retention in wheat, resulting in a decrease in proline and soluble protein levels while maintaining the integrity of macromolecules within the cell. Consequently, field experiments demonstrated that the ZnPB nanozyme increased winter wheat yield by 12.15 %, while also significantly enhancing its nutritional quality. This research offers a promising approach to improving the salinity tolerance of wheat, while also providing insights into its practical application.


Assuntos
Ferrocianetos , Tolerância ao Sal , Sementes , Triticum , Zinco , Triticum/efeitos dos fármacos , Ferrocianetos/química , Zinco/química , Zinco/farmacologia , Tolerância ao Sal/efeitos dos fármacos , Sementes/efeitos dos fármacos , Peroxidase/metabolismo , Sódio/metabolismo , Espécies Reativas de Oxigênio/metabolismo
7.
Pol Merkur Lekarski ; 52(2): 178-188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38642353

RESUMO

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.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias do Colo , Isatina , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Vorinostat/farmacologia , Isatina/farmacologia , Linhagem Celular Tumoral , Amidas/farmacologia , Desenho de Fármacos , Antineoplásicos/farmacologia , Sulfonamidas/farmacologia , Zinco/metabolismo , Zinco/farmacologia , Proliferação de Células , Estrutura Molecular
8.
Int J Mol Sci ; 25(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38612821

RESUMO

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.


Assuntos
Complexos de Coordenação , Zinco , Zinco/farmacologia , Ligantes , Bases de Schiff/farmacologia , Nitratos , Complexos de Coordenação/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Plâncton
9.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673887

RESUMO

Zinc is an essential trace element that plays a crucial role in T cell immunity. During T cell activation, zinc is not only structurally important, but zinc signals can also act as a second messenger. This research investigates zinc signals in T cell activation and their function in T helper cell 1 differentiation. For this purpose, peripheral blood mononuclear cells were activated via the T cell receptor-CD3 complex, and via CD28 as a costimulatory signal. Fast and long-term changes in intracellular zinc and calcium were monitored by flow cytometry. Further, interferon (IFN)-γ was analyzed to investigate the differentiation into T helper 1 cells. We show that fast zinc fluxes are induced via CD3. Also, the intracellular zinc concentration dramatically increases 72 h after anti-CD3 and anti-CD28 stimulation, which goes along with the high release of IFN-γ. Interestingly, we found that zinc signals can function as a costimulatory signal for T helper cell 1 differentiation when T cells are activated only via CD3. These results demonstrate the importance of zinc signaling alongside calcium signaling in T cell differentiation.


Assuntos
Antígenos CD28 , Complexo CD3 , Diferenciação Celular , Interferon gama , Ativação Linfocitária , Zinco , Humanos , Zinco/metabolismo , Zinco/farmacologia , Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Diferenciação Celular/efeitos dos fármacos , Interferon gama/metabolismo , Ionóforos/farmacologia , Linfócitos T/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Transdução de Sinais/efeitos dos fármacos , Cálcio/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/efeitos dos fármacos
10.
Medicina (Kaunas) ; 60(4)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38674257

RESUMO

Background and Objectives: The purpose of this study was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally induced with acetaminophen (AAPh) and potentiated by a ciprofloxacin addition in rats. Material and Methods: The experiment was performed on five animal groups: group 1-control, treated for 6 weeks with normal saline, 1 mL/kg; group 2-AAPh, treated for 6 weeks with AAPh, 100 mg/kg/day; group 3-AAPh + C, treated for 6 weeks with AAPh 100 mg/kg/day and ciprofloxacin 50 mg/kg/day, only in the last 14 days of the experiment; group 4-AAPh + C + Mg, with the same treatment as group 3, but in the last 14 days, MgCl2 10 mg/ kg/day was added; and group 5-AAPh + C + Zn, with the same treatment as group 3, but in the last 14 days, zinc gluconate (ZnG), 10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (p < 0.001 group 2 vs. group 1 for all mentioned parameters). Furthermore, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, at 0.001 < p < 0.01 and 0.01 < p < 0.05, respectively). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days, resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine (0.01 < p < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against the increase in liver enzymes, and a more pronounced protection against the increase in serum urea and creatinine (0.001 < p < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < p < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in the case of ZnG, to a higher extent, especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < p < 0.05 group 5 vs. group 4). Conclusions: This study presents further proof for the beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney's function, and the antioxidant profile improvement has a key role, especially in the case of zinc gluconate.


Assuntos
Acetaminofen , Ciprofloxacina , Gluconatos , Ratos Wistar , Animais , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Ratos , Gluconatos/farmacologia , Gluconatos/uso terapêutico , Masculino , Zinco/farmacologia , Zinco/uso terapêutico , Rim/efeitos dos fármacos , Magnésio/uso terapêutico , Magnésio/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Cloreto de Magnésio/farmacologia , Cloreto de Magnésio/uso terapêutico , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Sinergismo Farmacológico
11.
Redox Rep ; 29(1): 2341537, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38629506

RESUMO

BACKGROUND: Acrylamide is a toxic substance formed in some foods that require high-temperature cooking processes and has been implicated as a gonadotoxic agent. Zinc, on the other hand, is a known antioxidant with fertility-enhancing properties. Hence, this study was designed to explore the possible ameliorative effect of zinc in acrylamide-induced gonadotoxicity. METHODS: Twenty-four male Wistar rats were randomized into control, acrylamide (10 mg/kg of acrylamide), acrylamide + 1 mg/kg of zinc, and acrylamide + 3 mg/kg of zinc. The administration was via the oral route and lasted for 56 days. RESULTS: Zinc treatment ameliorated acrylamide-impaired sperm quality, normal testicular histoarchitecture, and hormonal balance, which was accompanied by increased testicular malondialdehyde and interleukin-1ß and decreased testicular superoxide dismutase (SOD) and catalase (CAT). Furthermore, zinc prevented acrylamide-induced downregulation of testicular nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (BCl2) expression and upregulation of testicular nuclear factor kappa B (NF-κB) and bcl-2-like protein 4 (bax) expression. CONCLUSION: In conclusion, zinc may protect against acrylamide-induced testicular toxicity, mediated by its antioxidant, anti-inflammatory, and antiapoptotic effects.


Assuntos
Antioxidantes , Apoptose , Estresse Oxidativo , Transdução de Sinais , Zinco , Animais , Masculino , Ratos , Acrilamida/toxicidade , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Ratos Wistar , Sêmen/metabolismo , Transdução de Sinais/efeitos dos fármacos , Zinco/farmacologia
12.
Nanotechnology ; 35(30)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38663375

RESUMO

In this research, we utilize porous tantalum, known for its outstanding elastic modulus and biological properties, as a base material in biomedical applications. The human skeletal system is rich in elements like Ca and Zn. The role of Zn is crucial for achieving a spectrum of sterilizing effects, while Ca is known to effectively enhance cell differentiation and boost cellular activity. The focus of this study is the modification of porous tantalum using a hydrothermal method to synthesize Ca2+/Zn2+-doped Ta2O5nanorods. These nanorods are subjected to extensive characterization techniques to confirm their structure and composition. Additionally, their biological performance is evaluated through a range of tests, including antibacterial assessments, MTT assays, and bacteria/cell scanning electron microscopy (SEM) analyses. The objective is to determine the most effective method of surface modification for porous tantalum, thereby laying a foundational theoretical framework for its surface enhancement.


Assuntos
Antibacterianos , Cálcio , Tantálio , Zinco , Tantálio/química , Antibacterianos/farmacologia , Antibacterianos/química , Zinco/química , Zinco/farmacologia , Cálcio/química , Humanos , Staphylococcus aureus/efeitos dos fármacos , Propriedades de Superfície , Porosidade , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana
13.
Biomed Pharmacother ; 174: 116525, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599057

RESUMO

PURPOSE: We previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. METHODS: The streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. RESULTS: The determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. CONCLUSIONS: The results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.


Assuntos
Antioxidantes , Ácido Ascórbico , Glicemia , Diabetes Mellitus Experimental , Resistência à Insulina , Lipídeos , Lisina , Ratos Wistar , Zinco , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Masculino , Ácido Ascórbico/farmacologia , Ácido Ascórbico/administração & dosagem , Lisina/farmacologia , Lisina/administração & dosagem , Zinco/farmacologia , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Ratos , Lipídeos/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estreptozocina , Insulina/sangue , Quimioterapia Combinada
14.
Nat Commun ; 15(1): 3131, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605012

RESUMO

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.


Assuntos
Osteogênese , Alicerces Teciduais , Osteogênese/fisiologia , Alicerces Teciduais/química , Porosidade , Impressão Tridimensional , Zinco/farmacologia
15.
Dalton Trans ; 53(17): 7561-7570, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38606466

RESUMO

This work focuses on the relationship between the coordination chemistry and antimicrobial activity of Zn(II) and Cu(II) complexes of histatin 5 and the products of its hydrolysis: its N-terminal fragment (histatin 5-8) and C-terminal fragment (histatin 8). Cu(II) coordinates in an albumin-like binding mode and Zn(II) binds to up to 3 His imidazoles. The antimicrobial activity of histatins and their metal complexes (i) strongly depends on pH - they are more active at pH 5.4 than at 7.4; (ii) the complexes and ligands alone are more effective in eradicating Gram-positive bacteria than the Gram-negative ones, and (iii) Zn(II) coordination is able to change the structure of the N-terminal region of histatin 5 (histatin 5-8) and moderately increase all of the studied histatins' antimicrobial potency.


Assuntos
Complexos de Coordenação , Cobre , Histatinas , Testes de Sensibilidade Microbiana , Zinco , Histatinas/química , Histatinas/farmacologia , Hidrólise , Concentração de Íons de Hidrogênio , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Cobre/química , Cobre/farmacologia , Zinco/química , Zinco/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Bactérias Gram-Negativas/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química
16.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38430558

RESUMO

To investigate effects of inorganic or complexed trace mineral source (zinc, copper, manganese, and cobalt) on receiving period performance and morbidity, crossbred beef heifer calves (n = 287) arriving on three delivery dates were used in a 42-d receiving trial. Heifers were processed after arrival, stratified by day -1 body weights (BW) and allocated randomly to eight pens (11 to 13 heifers/pen, 24 pens total). Within truckload, pens were assigned randomly to dietary treatment (n = 12 pens/treatment). Heifers were housed on 0.42-ha grass paddocks, provided ad libitum bermudagrass hay and provided dietary treatments in grain supplements fed daily. Treatments consisted of supplemental zinc (360 mg/d), copper (125 mg/d), manganese (200 mg/d), and cobalt (12 mg/d) from complexed (Zinpro Availa 4, Zinpro Corp. Eden Prairie, MN) or inorganic sources (sulfates). Heifers were observed daily for clinical bovine respiratory disease (BRD). If presenting BRD symptoms and rectal temperature ≥ 40 °C, heifers were deemed morbid and treated with antibiotics. Six heifers/pen were bled to determine serum haptoglobin concentrations on days 0, 14, and 28. Liver biopsies were taken on day 5 ±â€…2 and 43 ±â€…1 from three calves selected randomly from each pen for mineral status comparisons. Statistical analyses were performed using the MIXED, GLIMMIX, and repeated measures procedures of SAS 9.4 with truckload as a random effect and pen within truckload specified as subject. There tended to be a treatment by day interaction for BW (P = 0.07). Heifer BW did not differ on day 0 (P = 0.82) and day 14 (P = 0.36), but heifers fed complexed trace minerals had greater BW on day 28 (P = 0.04) and day 42 (P = 0.05). Overall average daily gains were greater for heifers fed complexed trace minerals (P = 0.05; 0.78 vs. 0.70 kg, SE = 0.03). Heifers supplemented with inorganic trace minerals had greater BRD incidence (P = 0.03; 58 vs. 46%, SE = 3.6). Haptoglobin concentrations decreased throughout the trial (P < 0.001), and heifers fed complexed trace minerals tended to have a decrease in haptoglobin concentrations (P = 0.07). The source of trace mineral supplementation had no effect (P ≥ 0.20) on liver mineral concentrations and there were no treatment × day interactions (P ≥ 0.35). In conclusion, supplementing diets for the first 42 d after arrival with complexed trace mineral sources improved heifer performance as compared to heifers supplemented with inorganic trace minerals.


Issues associated with health and management of newly received cattle continue to pose significant animal welfare and economic challenges for the beef industry. Diagnosis of bovine respiratory disease, accompanied with poor growth performance, can be addressed by nutritional intervention in receiving cattle. Trace mineral inclusion in receiving rations is vital to calf performance. There are numerous sources of trace mineral supplements that exist commercially for cattle and their effects on immune function, growth, and performance measures were evaluated. Organic trace mineral supplements are being used in replacement of inorganic salts due to potentially greater bioavailability and functionality. An organic source that is commonly used are amino acid complexes. Replacing inorganic sources with complexed sources of trace minerals (zinc, copper, manganese, and cobalt) improved growth performance and decreased sickness during the 42-d receiving study.


Assuntos
Oligoelementos , Bovinos , Animais , Feminino , Oligoelementos/farmacologia , Manganês/farmacologia , Cobre/farmacologia , Haptoglobinas/análise , Suplementos Nutricionais , Minerais/farmacologia , Zinco/farmacologia , Cobalto/farmacologia , Dieta/veterinária , Peso Corporal , Ração Animal/análise
17.
Genes (Basel) ; 15(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38540393

RESUMO

Lipophagy is a selective autophagy that regulates lipid metabolism and reduces hepatic lipid deposition. However, the underlying mechanism has not been understood in fish. In this study, we used micronutrient zinc (Zn) as a regulator of autophagy and lipid metabolism and found that Ras-related protein 7 (rab7) was involved in Zn-induced lipophagy in hepatocytes of yellow catfish Pelteobagrus pelteobagrus. We then characterized the rab7 promoter and identified binding sites for a series of transcription factors, including Forkhead box O3 (FOXO3). Site mutation experiments showed that the -1358/-1369 bp FOXO3 binding site was responsible for Zn-induced transcriptional activation of rab7. Further studies showed that inhibition of rab7 significantly inhibited Zn-induced lipid degradation by lipophagy. Moreover, rab7 inhibitor also mitigated the Zn-induced increase of cpt1α and acadm expression. Our results suggested that Zn exerts its lipid-lowering effect partly through rab7-mediated lipophagy and FA ß-oxidation in hepatocytes. Overall, our findings provide novel insights into the FOXO3/rab7 axis in lipophagy regulation and enhance the understanding of lipid metabolism by micronutrient Zn, which may help to reduce excessive lipid accumulation in fish.


Assuntos
Peixes-Gato , Zinco , Animais , Zinco/farmacologia , Metabolismo dos Lipídeos/genética , Peixes-Gato/genética , Peixes-Gato/metabolismo , Lipídeos , Autofagia/genética , Micronutrientes/metabolismo
18.
Nutrients ; 16(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38542798

RESUMO

A balanced microbiota-microorganisms that live in the gut-is crucial in the early years of a child's life, while dysbiosis-altered microbiota-has been linked to the development of various diseases. Probiotics, such as Alkalihalobacillus clausii, are commonly used to restore the balance of gut microbiota and have shown additional antimicrobial and immunomodulatory properties. Intake of micronutrients can affect the structure and function of the gut barrier and of the microbiota by having multiple effects on cellular metabolism (e.g., immunomodulation, gene expression, and support structure proteins). An inadequate zinc intake increases the risk of deficiency and associated immune dysfunctions; it is responsible for an increased risk of developing gastrointestinal diseases, respiratory infections, and stunting. Paediatric zinc deficiency is a public health concern in many countries, especially in low-income areas. Currently, zinc supplementation is used to treat childhood diarrhoea. This review examines how combining A. clausii and zinc could improve dysbiosis, gut health, and immunity. It suggests that this combination could be used to prevent and treat infectious diseases and diarrhoea in children up to adolescence.


Assuntos
Microbioma Gastrointestinal , Probióticos , Humanos , Criança , Zinco/farmacologia , Disbiose , Diarreia/tratamento farmacológico
19.
Curr Microbiol ; 81(5): 119, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526674

RESUMO

Talaromyces marneffei is an opportunistic pathogenic fungus that mainly affects HIV-positive individuals endemic to Southeast Asia and China. Increasing efforts have been made in the pathogenic mechanism and host interactions understanding of this pathogen in the last two decades; however, there are still no conclusions on how T. marneffei was transmitted from the donor bamboo rats to humans. A perception that the failure of fungus isolation from soil was attributed to the low salt tolerance of T. marneffei. Therefore, the effect of environmental fluctuations in fungal growth and development is fundamental for the characterization of its origin and fungal biology understanding. Herein, we characterized high osmolarity, pH, metal ions, nutrients, and oxidative stress have versatile effects on T. marneffei hyphal or yeast growth, conidia generation, and pigment production. Among these, high pH, low glucose amounts, and the inorganic nitrogen ammonium tartrate stimulated the red pigment production, whereas high osmolarity, high pH, and the inorganic nitrogen sodium nitrate could significantly accelerate the conidia generation. Specifically, zinc starvation repressed conidia generation and prevented the wrinkled yeast colony formation, indicating the function of zinc regulators in pathogenicity regulation. Since conidia are recognized as the infectious propagules, the effects characterization of different environmental factors in T. marneffei morphology in this work will not only expand the growth and pathogenic biology understanding of the fungus but also provide more clues for the T. marneffei infection transmission origin investigation.


Assuntos
Micoses , Saccharomyces cerevisiae , Talaromyces , Humanos , Nitrogênio , Zinco/farmacologia
20.
Int J Biol Macromol ; 265(Pt 2): 131156, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38537862

RESUMO

PTEN-induced putative kinase 1 (PINK1) is a key regulator of mitophagy, however, the relevant information remains poorly understood on aquatic animals. Here, a PINK1 gene was cloned, characterized and functionally studied in yellow catfish. PINK1 encoded a protein containing 570 amino acids, 2 functional domains. High fat (15.66%) fed fish showed a downregulation trend of liver PINK1 expression than that of normal fat (10.14%) group, and was reversed by the addition of Zn. In the in vitro study, high fat (HF) can increase lipid deposition and decrease by addition Zn (HFZ) in hepatocytes, whereas above phenomena reversed by overexpression/interference of PINK1, respectively. In addition, the addition of Zn can significantly affect mitochondrial activity, increase mitophagy, and improve the antioxidant activity of hepatocytes. Together, these findings illustrated that yellow catfish PINK1 is conserve, and it participated in mitochondria control of fish. These findings indicate Zn could alleviate high fat-induced hepatic lipid deposition of fish by activating PINK1-mediated mitophagy and provide basis for further exploring new approach for decreasing lipid deposition in fish products during aquaculture.


Assuntos
Peixes-Gato , Zinco , Animais , Zinco/farmacologia , Zinco/metabolismo , Metabolismo dos Lipídeos , Peixes-Gato/genética , Peixes-Gato/metabolismo , Fígado/metabolismo , Proteínas Quinases/metabolismo , Lipídeos
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