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1.
Theriogenology ; 221: 18-24, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521006

RESUMO

Zinc (Zn) plays essential roles in numerous cellular processes. However, there is limited understanding of Zn homeostasis within the bovine reproductive system. This study investigated the influence of estradiol (E2) and progesterone (P4) on Zn transporter expression and intracellular free Zn levels in bovine oviduct epithelial cells (BOEC). For this purpose, cells were harvested from slaughtered cows and cultured in vitro. Intracellular Zn concentrations were measured using FluoZin-3AM staining, while real-time polymerase chain reaction assessed Zn transporter gene expression and quantification. Overall, our results confirmed the gene expression of all the evaluated Zn transporters (ZIP6, ZIP8, ZIP14, ZnT3, ZnT7 and ZnT9), denoted and the active role of E2 and P4 in intracellular Zn regulation. Our findings suggest an interaction between Zn, E2 and P4.


Assuntos
Proteínas de Transporte , Progesterona , Zinco , Feminino , Bovinos , Animais , Progesterona/farmacologia , Progesterona/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Oviductos/metabolismo , Células Epiteliais/metabolismo , Estrogênios/farmacologia
2.
Theriogenology ; 221: 47-58, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38554613

RESUMO

Zinc, an essential trace mineral, exerts a pivotal influence in various biological processes. Through zinc concentration analysis, we found that the zinc concentration in the bovine embryo in vitro culture (IVC) medium was significantly lower than that in bovine follicular fluid. Therefore, this study explored the impact of zinc sulfate on IVC bovine embryo development and investigated the underlying mechanism. The results revealed a significant decline in zygote cleavage and blastocyst development rates when zinc deficiency was induced using zinc chelator N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) in culture medium during embryo in vitro culture. The influence of zinc-deficiency was time-dependent. Conversely, supplementing 0.8 µg/mL zinc sulfate to culture medium (CM) increased the cleavage and blastocyst formation rate significantly. Moreover, this supplementation reduced reactive oxygen species (ROS) levels, elevated the glutathione (GSH) levels in blastocysts, upregulated the mRNA expression of antioxidase-related genes, and activated the Nrf2-Keap1-ARE signaling pathways. Furthermore, 0.8 µg/mL zinc sulfate enhanced mitochondrial membrane potential, maintained DNA stability, and enhanced the quality of bovine (in vitro fertilization) IVF blastocysts. In conclusion, the addition of 0.8 µg/mL zinc sulfate to CM could enhance the antioxidant capacity, activates the Nrf2-Keap1-ARE signaling pathways, augment mitochondrial membrane potential, and stabilizes DNA, ultimately improving blastocyst quality and in vitro bovine embryo development.


Assuntos
Antioxidantes , Zinco , Feminino , Animais , Bovinos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Zinco/farmacologia , Zinco/metabolismo , Sulfato de Zinco/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Técnicas de Cultura Embrionária/veterinária , Desenvolvimento Embrionário , Fertilização In Vitro/veterinária , Blastocisto/fisiologia , Glutationa/metabolismo , DNA/metabolismo
3.
J Biomed Mater Res B Appl Biomater ; 112(3): e35395, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38433609

RESUMO

6-Mercaptopurine (6MP) is commonly used in the treatment of acute lymphoblastic leukemia as an important agent in maintenance therapy. Despite its therapeutic benefits, 6MP has some limitations during therapy. Taking into account the disadvantages during 6MP therapy, there is a great need to create an appropriate delivery system for this drug. 6MP contains in its structure nitrogen and sulfur atoms capable of forming coordination compounds with metal ions, for example zinc. Therefore, in this work, we prepared biocompatible hydroxyapatite (HAp) doped with zinc ions, and used it as a carrier for 6MP. Doped HAp has not been used as a carrier for this drug before. The work proved that the prepared carrier-drug system has a particle size of about 130 nm, which indicates its potential for intravenous delivery. In addition, in an acidic environment (imitating cancer cells), the carrier agglomerates allow targeted release of the drug. The drug is evenly distributed, which indicates that the doses released from it will always be comparable. The release of the drug in a neutral environment is long-lasting in controlled doses, whereas in an acidic environment it is immediate. The obtained results indicate the high potential of the material in both slow-release and cancer-targeted release of 6MP.


Assuntos
Antineoplásicos , Mercaptopurina , Mercaptopurina/farmacologia , Zinco/farmacologia , Sistemas de Liberação de Medicamentos , Durapatita/farmacologia , Antineoplásicos/farmacologia , Íons , Concentração de Íons de Hidrogênio
4.
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
5.
Int Immunopharmacol ; 131: 111868, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38493692

RESUMO

Mitochondrial injury, neuronal apoptosis and phenotypic transformation of macrophages are the main mechanisms of spinal cord injury. Based on the Prussian blue nanomase's strong ability to clear free radicals, the treatment of spinal cord injury with nano-zirconium (Pb-Zr) was carried out. The disease treatment strategy based on nanomaterials has excellent therapeutic effect, and Prussian blue analogs have good therapeutic properties, so the application prospects of Prussian blue analogs is broad. From the point of view of Prussian blue content, improving the presence of zirconium in the microenvironment significantly increased the activity of Prussian blue. Prussian Blue zirconium significantly improved lipopolysaccharide (LPS) and interferon (IFN-γ) induced neuronal cell (pc12 cells) and macrophage dysfunction by improving oxidative stress, inflammation, and apoptosis in the microenvironment. It can promote the recovery of motor function after spinal cord injury. In vivo experiments, it shows that Prussian blue zirconium can improve inflammation, apoptosis and oxidative stress of spinal cord tissue, promote regenerative therapy after spinal cord injury, and improve motor function. Moreover, it has been reported that high-priced Zr4+ cations can regulate the deposition and nucleation behavior of Zn2+ in high-performance zinc metal anodes. Therefore, we propose the hypothesis that Pb-Zr modulates Zn2+ be used to promote recovery from spinal cord injury. The results show that nanomaterial is beneficial in the treatment of spinal cord injury. This study provides a good prospect for the application of spinal cord injury treatment. It also provides an important feasibility for subsequent clinical conversions.


Assuntos
Ferrocianetos , Chumbo , Traumatismos da Medula Espinal , Ratos , Animais , Chumbo/farmacologia , Chumbo/uso terapêutico , Zircônio/uso terapêutico , Zircônio/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal , Inflamação/tratamento farmacológico , Zinco/uso terapêutico , Zinco/farmacologia
6.
Biomed Mater ; 19(3)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38518361

RESUMO

Rapid bone regeneration in implants is important for successful transplantation. In this regard, we report the development of calcium silicate/zinc silicate (CS/ZS) dual-compound-incorporated calcium phosphate cement (CPC) scaffolds with a three-dimensional poly (lactic-co-glycolic acid) network that synergistically promote bone regeneration.In vitroresults demonstrated that the incorporation of CS/ZS dual compounds into the CPC significantly promoted the osteogenic differentiation of stem cells compared to the addition of CS or ZS alone. Moreover, the bone-regeneration efficacy of the composite scaffolds was validated by filling in femur condyle defects in rabbits, which showed that the scaffolds with CS and ZS possessed a great bone repair effect, as evidenced by more new bone formation and a faster scaffold biodegradation compared to the scaffold with CS alone.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Compostos de Zinco , Animais , Coelhos , Tecidos Suporte , Zinco/farmacologia , Proliferação de Células , Compostos de Cálcio , Regeneração Óssea , Silicatos , Fosfatos de Cálcio/farmacologia
7.
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
8.
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
9.
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
10.
Clin Oral Implants Res ; 35(4): 427-442, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38314615

RESUMO

OBJECTIVE: This study aimed to synthesize zinc-incorporated nanowires structure modified titanium implant surface (Zn-NW-Ti) and explore its superior osteogenic and antibacterial properties in vitro and in vivo. MATERIALS AND METHODS: Zn-NW-Ti was synthesized via displacement reactions between zinc sulfate solutions and the titanium (Ti) surface, which was pretreated by hydrofluoric acid etching and hyperthermal alkalinization. The physicochemical properties of the Zn-NW-Ti surface were examined. Moreover, the biological effects of Zn-NW-Ti on MC3T3-E1 cells and its antibacterial property against oral pathogenic bacteria (Staphylococcus aureus, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) compared with sandblasted and acid-etched Ti (SLA-Ti) and nanowires modified Ti (NW-Ti) surface were assessed. Zn-NW-Ti and SLA-Ti modified implants were inserted into the anterior extraction socket of the rabbit mandible with or without exposure to the mixed bacterial solution (S. aureus, P. gingivalis, and A. actinomycetemcomitans) to investigate the osteointegration and antibacterial performance via radiographic and histomorphometric analysis. RESULTS: The Zn-NW-Ti surface was successfully prepared. The resultant titanium surface appeared as a nanowires structure with hydrophilicity, from which zinc ions were released in an effective concentration range. The Zn-NW-Ti surface performed better in facilitating the adhesion, proliferation, and differentiation of MC3T3-E1 cells while inhibiting the colonization of bacteria compared with SLA-Ti and NW-Ti surface. The Zn-NW-Ti implant exhibited enhanced osseointegration in vivo, which was attributed to increased osteogenic activity and reduced bacterial-induced inflammation compared with the SLA-Ti implant. CONCLUSIONS: The Zn-incorporated nanowires structure modified titanium implant surface exhibited improvements in osteogenic and antibacterial properties, which optimized osteointegration in comparison with SLA titanium implant surface.


Assuntos
Implantes Dentários , Nanofios , Animais , Coelhos , Titânio/farmacologia , Titânio/química , Staphylococcus aureus , Antibacterianos/farmacologia , Osseointegração , Bactérias , Zinco/química , Zinco/farmacologia , Propriedades de Superfície , Osteogênese
11.
BMC Plant Biol ; 24(1): 138, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38408911

RESUMO

Micronutrient application has a crucial role in mitigating salinity stress in crop plants. This study was carried out to investigate the effect of zinc (Zn) and boron (B) as foliar applications on fenugreek growth and physiology under salt stress (0 and 120 mM). After 35 days of salt treatments, three levels of zinc (0, 50, and 100 ppm) and two levels of boron (0 and 2 ppm) were applied as a foliar application. Salinity significantly reduced root length (72.7%) and shoot length (33.9%), plant height (36%), leaf area (37%), root fresh weight (48%) and shoot fresh weight (75%), root dry weight (80%) and shoot dry weight (67%), photosynthetic pigments (78%), number of branches (50%), and seeds per pod (56%). Fenugreek's growth and physiology were improved by foliar spray of zinc and boron, which increased the length of the shoot (6%) and root length (2%), fresh root weight (18%), and dry root weight (8%), and chlorophyll a (1%), chlorophyll b (25%), total soluble protein content (3%), shoot calcium (9%) and potassium (5%) contents by significantly decreasing sodium ion (11%) content. Moreover, 100 ppm of Zn and 2 ppm of B enhanced the growth and physiology of fenugreek by reducing the effect of salt stress. Overall, boron and zinc foliar spray is suggested for improvement in fenugreek growth under salinity stress.


Assuntos
Trigonella , Zinco , Boro/metabolismo , Boro/farmacologia , Clorofila A/metabolismo , Estresse Salino , Tensoativos/metabolismo , Tensoativos/farmacologia , Trigonella/metabolismo , Zinco/metabolismo , Zinco/farmacologia
12.
Nanoscale ; 16(10): 5383-5394, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38375749

RESUMO

Antifungal resistance has become a very serious concern, and Candida albicans is considered one of the most opportunistic fungal pathogens responsible for several human infections. In this context, the use of new antifungal agents such as zinc-based layered double hydroxides to fight such fungal pathogens is considered one possible means to help limit the problem of antifungal resistance. In this study, we show that ZnAl LDH nanoparticles exhibit remarkable antifungal properties against C. albicans and cause serious cell wall damage, as revealed by growth tests and atomic force microscopy (AFM) imaging. To further link the antifungal activity of ZnAl LDHs to their adhesive behaviors toward C. albicans cells, AFM-based single-cell spectroscopy and single-particle force spectroscopy were used to probe the nanoscale adhesive interactions. The force spectroscopy analysis revealed that antimicrobial ZnAl LDHs exhibit specific surface interactions with C. albicans cells, demonstrating remarkable force magnitudes and adhesion frequencies in comparison with non-antifungal negative controls, e.g., Al-coated substrates and MgAl LDHs, which showed limited interactions with C. albicans cells. Force signatures suggest that such adhesive interactions may be attributed to the presence of agglutinin-like sequence (Als) adhesive proteins at the cell wall surface of C. albicans cells. Our findings propose the presence of a strong correlation between the antifungal effect provided by ZnAl LDHs and their nanoscale adhesive interactions with C. albicans cells at both the single-cell and single-particle levels. Therefore, ZnAl LDHs could interact with C. albicans fungal pathogens by specific adhesive interactions through which they adhere to fungal cells, leading to their damage and subsequent growth inhibition.


Assuntos
Antifúngicos , Candida albicans , Compostos de Zinco , Humanos , Antifúngicos/farmacologia , Hidróxidos/farmacologia , Hidróxidos/química , Zinco/farmacologia , Zinco/química , Análise Espectral
13.
Dalton Trans ; 53(10): 4512-4525, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38348683

RESUMO

A new hexanuclear Zn(II) complex with the ligand 2,2'-(piperazine-1,4-diyl)bis(ethan-1-amine), [L3Zn6(OH)6][ClO4]6·3MeOH·7H2O, was synthesized. The crystal structure of this complex showed that each Zn atom is in a distorted tetrahedral coordination environment, surrounded by two nitrogen atoms from each ligand and two hydroxide groups, each of which bridges to another Zn atom. The anticancer activities of the ligand and its metal complex against the breast cancer cell line (MCF-7) indicated that the zinc complex had a greater anticancer activity. The free ligand and its metal complex were evaluated for antioxidant activity using the DPPH scavenging method. In addition, the antibacterial activities of both compounds were screened against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The interaction of these compounds with DNA and AChE was also investigated using molecular docking.


Assuntos
Anti-Infecciosos , Complexos de Coordenação , Antioxidantes/farmacologia , Antioxidantes/química , Simulação de Acoplamento Molecular , Raios X , Ligantes , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Complexos de Coordenação/química , Zinco/farmacologia , Zinco/química , Testes de Sensibilidade Microbiana
14.
Nutrients ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38398836

RESUMO

Eggs, with their high nutritional value, are great carriers for enriching nutrients. In this study, selenium- and/or zinc-enriched eggs (SZE) were obtained and their effects on ameliorating oxidative stress injury, alleviating cognitive impairment, and maintaining intestinal flora balance in a D-gal-induced aging mice model were investigated. As determined by the Y-maze test, SZE restored the learning and memory abilities and increased the Ach level and AChE activity of aging mice (p < 0.05). Meanwhile, supplementation of low-dose SZE increased antioxidant levels and decreased inflammation levels (p < 0.05). High-dose SZE increased anti-inflammatory levels but were less effective than low dose. Additionally, SZE maintained the intestinal flora balance and significantly increased the ratio of Firmicutes and Bacteroidota. Blautia, as a probiotic, was negatively correlated with pro-inflammatory factors and positively correlated with antioxidant levels (p < 0.05). These results suggest that SZE might improve organ damage and cognitive function by attenuating oxidative stress and inflammatory response and maintaining healthy gut flora.


Assuntos
Microbioma Gastrointestinal , Selênio , Camundongos , Animais , Selênio/farmacologia , Antioxidantes/farmacologia , Zinco/farmacologia , Estresse Oxidativo , Envelhecimento , Dieta , Galactose/farmacologia
15.
Nutrients ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38398842

RESUMO

Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient's dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI (p < 0.05), but no significant change was observed (p = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI.


Assuntos
Anemia , Hematínicos , Inibidores de Prolil-Hidrolase , Insuficiência Renal Crônica , Humanos , Hematínicos/farmacologia , Hematínicos/uso terapêutico , Anemia/tratamento farmacológico , Inibidores de Prolil-Hidrolase/farmacologia , Inibidores de Prolil-Hidrolase/uso terapêutico , Zinco/farmacologia , Zinco/uso terapêutico , Eritropoese , Prolil Hidroxilases/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Darbepoetina alfa/farmacologia , Darbepoetina alfa/uso terapêutico , Estudos Retrospectivos , Glicina/farmacologia , Suplementos Nutricionais
16.
Sci Rep ; 14(1): 4448, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396015

RESUMO

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96-2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03-0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15-0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR.


Assuntos
Antibacterianos , Anti-Infecciosos , Animais , Bovinos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Zinco/farmacologia , Escherichia coli , Farmacorresistência Bacteriana , Anti-Infecciosos/farmacologia , Enterococcus , Diarreia/tratamento farmacológico , Diarreia/veterinária , Diarreia/microbiologia , Compostos Orgânicos/farmacologia , Suplementos Nutricionais , Ciprofloxacina/farmacologia
17.
Carbohydr Polym ; 331: 121823, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38388030

RESUMO

Cellulose-based polymer scaffolds are highly diverse for designing and fabricating artificial bone substitutes. However, realizing the multi-biological functions of cellulose-based scaffolds has long been challenging. In this work, inspired by the structure and function of the extracellular matrix (ECM) of bone, we developed a novel yet feasible strategy to prepare ECM-like scaffolds with hybrid calcium/zinc mineralization. The 3D porous structure was formed via selective oxidation and freeze drying of bacterial cellulose. Following the principle of electrostatic interaction, calcium/zinc hybrid hydroxyapatite nucleated, crystallized, and precipitated on the 3D scaffold in simulated physiological conditions, which was well confirmed by morphology and composition analysis. Compared with alternative scaffold cohorts, this hybrid ion-loaded cellulose scaffold exhibited a pronounced elevation in alkaline phosphatase (ALP) activity, osteogenic gene expression, and cranial defect regeneration. Notably, the hybrid ion-loaded cellulose scaffold effectively fostered an M2 macrophage milieu and had a strong immune effect in vivo. In summary, this study developed a hybrid multifunctional cellulose-based scaffold that appropriately simulates the ECM to regulate immunomodulatory and osteogenic differentiation, setting a measure for artificial bone substitutes.


Assuntos
Substitutos Ósseos , Osteogênese , Osteogênese/genética , Cálcio/metabolismo , Tecidos Suporte/química , Celulose/farmacologia , Celulose/metabolismo , Zinco/farmacologia , Regeneração Óssea , Durapatita/metabolismo , Matriz Extracelular/metabolismo
18.
ACS Appl Mater Interfaces ; 16(8): 10565-10579, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38377563

RESUMO

Post-traumatic hemorrhage, which can result from accidents or battlefield injuries, is a significant global concern due to the high prehospital mortality rate. Substantial efforts have been made to develop hemostatic agents that can effectively reduce hemorrhage in the immediate aftermath of a traumatic event. The present study investigated the potential efficacy of Ca2+ and Zn2+ supplemented sodium alginate-based dry hemostatic particles (SA-CZ DHP) to manage excessive blood loss or post-traumatic hemorrhage. SA-CZ DHP were developed, followed by their physical and biochemical characterization, cytocompatibility and hemocompatibility testing, and critical evaluation of the hemostatic potential in vitro and in vivo. The safe SA-CZ DHP showed high absorption and accelerated blood clotting kinetics with reduced coagulation time (≈70%, p < 0.0001) in whole human blood, observed with insignificant hemolysis and uninterrupted RBC morphology. SA-CZ DHP significantly reduced the mean blood loss (≈90% in SD rats tail incision), and bleeding time (≈60% in BALB/c mice tail incision) was at par with commercially available Celox hemostatic granules. In conclusion, the biocompatible SA-CZ DHP exhibited rapid and effective management of excessive blood loss. It is also pertinent to note that the developed formulation could be a cost-effective alternative to its commercial counterparts.


Assuntos
Hemostáticos , Camundongos , Ratos , Humanos , Animais , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Hemostáticos/química , Alginatos/uso terapêutico , Alginatos/farmacologia , Cálcio , Zinco/uso terapêutico , Zinco/farmacologia , Ratos Sprague-Dawley , Hemorragia/tratamento farmacológico , Hemostasia
19.
Nanomedicine ; 57: 102739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341009

RESUMO

Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly-l-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.


Assuntos
Citocinas , Zinco , Animais , Coelhos , Zinco/farmacologia , Fator A de Crescimento do Endotélio Vascular , Preparações de Ação Retardada/farmacologia , Stents
20.
Biomater Adv ; 159: 213814, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38417206

RESUMO

Controllable preparation of materials with new structure has always been the top priority of polymer materials science research. Here, the supramolecular binding strategy is adopted to develop covalent organic frameworks (COFs) with novel structures and functions. Based on this, a two-dimensional crown-ether ring threaded covalent organic framework (COF), denoted as Crown-COPF with intrinsic photothermal (PTT) and photodynamic (PDT) therapeutic capacity, was facilely developed using crown-ether threaded rotaxane and porphyrin as building blocks. Crown-COPF with discrete mechanically interlocked blocks in the open pore could be used as a molecular machine, in which crown-ether served as the wheel sliding along the axle under the laser stimulation. As a result, Crown-COPF combining with the bactericidal power of crown ether displayed a significant photothermal and photodynamic antibacterial activity towards both the Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus), far exceeding the traditional Crown-free COF. Noteworthily, the bactericidal performance could be further enhanced via impregnation of Zn2+ ions (Crown-COPF-Zn) flexible coordinated with the multiple coordination sites (crown-ether, bipyridine, and porphyrin), which not only endow the positive charge with the skeleton, enhancing its ability to bind to the bacterial membrane, but also introduce the bactericidal ability of zinc ions. Notably, in vivo experiments on mice with back infections indicates Crown-COPF-Zn with self-adaptive multinuclear zinc center, could effectively promote the repairing of wounds. This study paves a new avenue for the effectively preparation of porous polymers with brand new structure, which provides opportunities for COF and mechanically interlocked polymers (MIPs) research and applications.


Assuntos
Éteres de Coroa , Ciclodextrinas , Estruturas Metalorgânicas , Poloxâmero , Porfirinas , Rotaxanos , Animais , Camundongos , Estruturas Metalorgânicas/farmacologia , Rotaxanos/farmacologia , Éteres de Coroa/farmacologia , Polímeros/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Íons , Zinco/farmacologia , Cicatrização
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