Research progress on surface modification of titanium implants by strontium ions / 口腔疾病防治

@#Traditional titanium implants do not completely meet the clinical requirements because they are bioinert. The surface of titanium implants, modified by strontium ions, can enhance osseointegration and reduce peri-implantitis. In this paper, the biological properties of titanium implant surfaces modified by strontium ions were reviewed. Strontium ions can be coated on the implant surface by hydrothermal treatment, electrochemical deposition, phosphate chemical conversion, flame-spraying, supramolecular self-assembly, magnetron sputtering, laser deposition and alkali etching. Implant surfaces modified by strontium ions can not only promote osteogenesis and early osseointegration but also inhibit bacterial growth and reduce postoperative infections. Even better osseointegration and antibacterial effects can be achieved when strontium ions are incorporated with other elements, such as silver, zinc, gallium, and calcium. However, most of the studies on the use of strontium ion-modified titanium implants are animal experiments and in vitro experiments, and the observation time is short compared with the actual service life of the implants. Thus, the conclusions obtained may be different from the actual clinical application, and the long-term effects need to be studied. In addition, the osteogenic effects of various modification methods also need to be compared. Future research can focus on the following points: ① to find efficient modification methods that can be widely used in the clinic; ②to study how to control the concentration of strontium ions near the implant to exert their biological function and reduce their toxic side effects; and ③ to conduct long-term follow-up clinical trials to observe their osteogenic and antibacterial effects.

Resveratrol promotes autophagy through zinc ion and induces cardiomyocyte protection / 中国药理学通报

Aim To investigate whether resveratrol (Resveratrol, Res) induces cardiomyocyte protection by increasing intracellular zinc ion and its possible signal mechanism. Methods H9c2 cells were routinely cultured and 2-deoxyglucose (2-DG) was used to establish an endoplasmic reticulum stress (ERS) model. The experiment was randomly divided into control group, 2-DG group, Res +2-DG group, TPEN + Res + 2-DG group and 3-MA + Res +2-DG group. Cell viability was detected by MTT and CCK-8; the expression levels of ERS molecular chaperone proteins glucose-regulated protein 78 (GRP78), glucose-regulated protein 94 (GRP94) and autophagy proteins LC3 II / I, p62 and p-AMPK were detected by Western blot; the expression of LC3 protein was measured by cellular immunofluorescence; the mitochondrial membrane potential (Aijjm) and the intracellular zinc ion level were measured by laser scanning confocal microscope. Results Compared with the control group, 2-DG reduced cell activity and resveratrol inhibited the changes caused by 2-DG, which was reversed by zinc chelator TPEN. 2-DG increased GRP78 and GRP94 expression and resveratrol inhibited the protein changes caused by 2-DG, which was reversed by TPEN. 2-DG increased the expression of LC3 II / I, p-AMPK and decreased the expression of p62, and resveratrol promoted the effect of 2-DG. 2-DG increased the fluorescence intensity of LC3, and resveratrol enhanced the effect of 2-DG, which was reversed by TPEN and 3-MA. 2-DG reduced the red fluorescence intensity of mitochondrial TMRE and green fluorescence intensity of intracellular zinc ions, and resveratrol inhibited these changes caused by 2-DG, which was also reversed by TPEN and 3-MA. The above differences were all statistically significant (P < 0. 05). Conclusion Resveratrol increases intracellular zinc to promote ERS-induced autophagy and prevent the mPTP opening in H9c2 cardiac cells.

Zinc ion concentration affects proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells / 中国组织工程研究

BACKGROUND: Zinc ion is a necessary metal trace element in human body, which plays an important role in inhibiting osteoclast activity and promoting osteogenic differentiation. However, the effect of zinc ion at different concentrations on osteogenic differentiation of rabbit bone marrow mesenchymal stem cells has been rarely studied. OBJECTIVE: To evaluate the effects of zinc ion at different concentrations on the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells for exploring the appropriate zinc ion concentration. METHODS: Bone marrow mesenchymal stem cells were extracted from the long bone marrow of rabbits and passaged. The cells were divided into six groups, including 10-4, 10-5, 10-6, 10-7 and 10-8 mol/L zinc ion groups, and blank control group. The cell proliferation activity was measured by Cell Counting Kit-8 and the growth curve was drawn. Alkaline Phosphatase Assay kit was used to evaluate the osteogenic differentiation ability of the cells, and the growth activity of the cells was shown by Live-Dead Cell Staining Kit. The mineralization ability of the cells was observed by alizarin red S staining. The expression of osteogenic genes was detected by fluorescence quantitative polymerase chain reaction. RESULTS AND CONCLUSION: The number of cells in each group showed an increasing trend with the prolongation of time except for the 10-4 mol/L zinc ion group. After 5 days of culture, the number of cells was highest in the 10-7 mol/L zinc ion group, but lowest in the 10-4 mol/L zinc ion group. Alkaline phosphatase activity was highest when zinc ion concentration was 10-7 mol/L, but lowest at the 10-4 mol/L zinc ion after cell culture for 14 days. The method of Live-Dead Cell Staining revealed the number of viable cells was highest in the 10-7 mol/L zinc ion group. All cells were almost dead in the 10-4 mol/L zinc ion group. Calcium nodule formation was visible, and the expression level of osteogenic genes was highest in the 10-7 mol/L zinc ion group after 14 days of cell culture. These findings suggest that zinc ion can effectively promote the proliferation and osteogenic differentiation of rabbit bone marrow mesenchymal stem cells in a certain concentration range. The promoting effects of zinc ion on proliferation, osteogenic induction and mineralization are strongest. Therefore, the addition of a suitable concentration of zinc ions in the medium is beneficial for the osteogenic differentiation of rabbit bone marrow mesenchymal stem cells.

Black phosphorus loaded with zinc ions for enhanced photothermal therapy of prostate cancer / 药学学报

Prostate cancer is the most common malignant tumor of male reproductive system, which seriously threatens men's health. It has been shown that the existence of zinc ions can inhibit the growth of prostate cancer cells. In addition, photothermal treatment of cancer is attracting more and more attention due to its high accuracy and efficiency. In this study, zinc ions loaded black phosphorus nanosheets (BP-Zn) were prepared, and the photothermal therapy efficiency of the system on human prostate cancer cells (PC-3) was evaluated. The inhibition effect of zinc ions on PC-3 cells was studied. It was demonstrated that the toxicity of zinc ions on PC-3 cells was concentration- and time-dependent. Moreover, it can be seen from in vitro photothermal therapy that the treatment effect of black phosphorus assisted by zinc ions is superior to that of black phosphorus alone. This study further studied the in vivo therapeutic effect of BP-Zn. The results once again confirmed that the combinational photothermal treatment of zinc ions and BP had excellent anti-tumor effect. The animal procedures were approved by the Animal Ethics Committee of Tsinghua Shenzhen International Graduate School.

Zinc Ion Inhibits Macrophage Foaming during Atherosclerosis / 中山大学学报(医学科学版)

@#【Objective】To investigate the effects of zinc on the formation of atherosclerotic macrophage foaming and plaque formation and its mechanism.【Methods】The macrophage foaming model was established by stimulating THP-1cells with oxLDL. The degree of foaming in different zinc concentrations of 0，30 and 60 μmol/Lwas detected by oil red Ostaining and the intake of lipid by foam cells was measured by DiI-oxLDL fluorescence. The relevant scavenger protein ex⁃pression of CD36，SR-A was detected by immunoblotting. The relative expression level of zinc ion transporters was detect⁃ed by real-time fluorescent quantitative PCR. ApoE-/- mice were randomly divided into 4 groups，the normal feed group（Chow group），the high-fat zinc-deficient group（HFD-ZnD），and the high-fat normal zinc group（HFD），high-fatand zinc-supplement group（HFD-ZnS），blood lipids and the protein of the mice aorta were detected in the 13 week.【Results】Compared with the normal zinc group，the oil red O density increased（P < 0.05），and add zinc ion decreased the intake of the DiI-oxLDL by foam cells（P < 0.01）. In the 0 μmol/L zinc group，the SR-A and CD36 protein expressionin the foam cells increased（P < 0.05）and 15μmol/L Zn2+ treatment before stimulating with oxLDL reduced the contentsof SR-A and CD36 proteins（P < 0.05）. Compared the oxLDL-treated group with the control group，the mRNA expres⁃sion levels of ZIP10，ZIP12 and ZIP14 increased，and the mRNA expression levels of ZIP4，ZIP7 and ZIP8 decreased（P < 0.05）；while the mRNA expression of ZnT4 was up-regulated（P < 0.01），and the mRNA expression of ZnT1 was down-regulated（P < 0.05）. Compared with Chow group，low density lipoprotein cholesterol（LDL-C），total cholesterol（TC）and triglyceride（TG）were increased in HFD group and HFD-ZnD group，respectively（P < 0.05）；HFD-ZnD group High-density lipoprotein cholesterol（HDL-C）was significantly elevated. Moreover，the LDL-C of the HFD-ZnS group was significantly lower than that of the HFD-ZnD group（P < 0.05）. The SR-A protein of the mice aorta of the HFD and HFD-ZnD group increased compared to the Chow group（P < 0.01），HFD-ZnS could restrain the increase（P < 0.05）. Compared with the Chow group，the ratio of plaque area in the aorta to the total arterial lumen area was significantly in⁃creased in the HFD-ZnD group（P < 0.01），and HFD-ZnS significantly inhibited this increase（P < 0.01）.【Conclusions】 Extracellular zinc deficiency aggravates lipid deposition in macrophages，and the mechanism may be regulated by up-reg⁃ulating the scavenger receptor CD36 and SR-A. Zinc ion transporters are involved in macrophage foaming and formation ofarterial plaques. Zinc deficiency can increase LDL-C and promote the increase of arterial plaque induced by high-fat diet.

A Novel Fluorescent Probe Based on Schiff Base for Dual Sensing of Zn2+and CN- / 分析化学

A novel Schiff base probe 4'-hydroxy-3'-((2-pyridin-2-ylmethylimino) methyl)-4-biphenyl carbonitrile (HPBC) for dual sensing of Zn2+and CN-was synthesized and characterized by various techniques such as UV-Vis, fluorescence, HRMS and NMR spectroscopy. HPBC was highly selective toward these two ions with different fluorescence signals in two different media. In EtOH-H2O(2:3,V/V;HEPES,pH 7.4),HPBC selectively bound Zn2+to form a 1:1 ligand/metal complex. Addition of Zn2+to the solution of HPBC resulted in a blue shift (△λ=15 nm) with a pronounced fluorescence enhancement at 468 nm, while there was no enhancement in the presence of other metal ions,especially Cd2+. HPBC displayed an"ON-OFF-ON"mode fluorescence change with alternative addition of Zn2+and EDTA. Hence, HPBC is a reversible and reusable sensor for Zn2+. The dynamic range of the assay is linear up to 4.0 μmol/L Zn2+ion and the limit of detection was 36.5 nmol/L,which was thousand fold lower than the WHO guideline (about 76 μmol/L) for drinking water. The fluorescence response of HPBC toward Zn2+was pH-dependent, and the maximal signal was observed at near neutral pH values, which makes it suitable for application in physiological conditions. Cell imaging studies demonstrate that this sensor is capable of sensing Zn2+in living cells. In DMSO-H2O (3:7,V/V) medium,addition of cyanide ion to HPBC led to deprotonation of the phenol hydrogen,resulting in a color change from colorless to pale yellow and a significant fluorescence enhancement at 510 nm. The probe exhibited high selectivity and sensitivity for CN- ion and the detection limit was 5.75×10-7mol/L. Finally,the use of a test strip of probe HPBC to detect cyanide was reported.

Effect of zinc ion on myocardial mitochondrial protection / 中国药学杂志

OBJECTIVE: To investigate the cardioprotective effect of exogenous zinc (Zn2+) on the mitochondrial pathway, and to explore its possible mechanism. METHODS: Rat heart tissue-derived H9c2 cardiac cells were cultured, and then randomly divided into control group, ZnCl2 group (1-20 μmol·L-1, 20 min), ZnCl2 plus inhibitor group [PI3K inhibitor LY294002, 10 μmol·L-1and mitochondrial ATP sensitive potassium channel (mKATP) inhibitor 5-HD, 0.5 mmol·L-1, inhibitors treated cells for 10 min and then ZnCl2 20 min] and inhibitor group (10 min). The mitochondrial permeability transition pore (mPTP) opening was evaluated by measuring mitochondrial membrane potential (ΔΨm). Tetramethylrhodamine ethyl ester (TMRE) diacetate fluorescence images were obtained with laser scanning confocal microscopy. GSK-3β and AKT phosphorylation were determined with Western blot. The cells were subjected to simulated ischemia/reperfusion injury, cell viability were determined with flow cytometry. Cells were transfected with constitutively active GSK-3β-S9A (GSK-3β-S9A) plasmid by Fugene 6 transfection kit, mPTP opening was evaluated by confocal microscopy. RESULTS: Compared with the normal, exposure of cells to H2O2 for 20 min caused a marked decrease in TMRE fluorescence, treatment of cells with different dose of Zn2+ prevented the loss of TMRE fluorescence caused by H2O2 with the peak at 10 μmol·L-1. Western blot showed that Zn2+ significantly enhanced the GSK-3β and AKT phosphorylation, the effect that was significantly reversed by LY294002, but not 5-HD. Compared with the normal, ischemia/reperfusion markedly reduced cell viability. Zn2+ applied at ischemia did not increase the cell viability, but significantly increased the cell viability when given at reperfusion. Zn2+ could mimic the specific mPTP inhibitor cyclosporin A (1 μmol·L-1) and prevent the mPTP opening, which was again reversed by LY294002 but not 5-HD. Zn2+ was not able to exert protection in cells transfected with the GSK-30-S9A. CONCLUSION: Zn2+ can induce myocardial mitochondrial protective effect by modulating the mPTP opening through the inactivation of GSK-3β via PI3K/AKT pathway. mKATP may not be involved in the action of Zn2+.

Efecto de adición de iones hierro y zinc sobre la producción de etanol de dos cepas recombinantes de Saccharomyces cerevisiae / The effect of adding iron and zinc ions to ethanol production from two recombinant Saccharomyces cerevisiae strains

La producción de etanol por fermentación es influenciada por la presencia de iones metálicos como hierro y zinc dado que son cofactores de la enzima alcohol deshidrogenasa. El estudio de este efecto permitiría identificar el comportamiento de los microorganismos fermentadores en sustratos industriales que contienen altas concentraciones de este tipo de iones. Este trabajo evaluó la producción de biomasa, los azúcares residuales y la producción de etanol por fermentación de tres cepas de S. cerevisiae, CBS8066, recombinantes GG570-CIBI y GG570-CIBII, bajo el efecto de la adición de hierro a 0, 50 y 150 M, y zinc a 0 y 50 M. Las cepas presentaron inhibición en la producción de biomasa y etanol bajo efecto de iones de hierro y zinc, siendo dicha inhibición mayor al estar en presencia de zinc o alta concentración de hierro. GG570-CIBI mostró disminución en producción de biomasa de 4 g/L y una caída en producción de etanol de 40% en el tratamiento 150 M hierro-50 M zinc (con respecto al tratamiento basal). GG570-CIBII fue la menos afectada con inhibición en la producción de etanol inferior a 11% a las 20 h de fermentación. Adicionalmente, presentó la mayor producción de etanol cuando hubo adición de 150 M Fe con o sin adición de zinc, siendo dicha producción entre un 9 y 14% superior a la de las cepas CBS8066 y GG570-CIBI respectivamente, bajo las mismas condiciones. Posteriormente, GG570-CIBII será evaluada en sustratos industriales debido a su menor inhibición en la producción de etanol, permitiendo así obtener mejores rendimientos.

The ethanol production by fermentation is influenced by the presence of metallic ions like iron and zinc because these are alcohol dehydrogenase enzyme cofactors. The study of this effect would allow for identifying the behavior of microorganisms in industrial substrates that contain high concentrations of this kind of ions. This work evaluated biomass production, residual sugars and ethanol production by fermentation of three S. cerevisiae strains, CBS8066, recombinants GG570-CIBI and GG570-CIBII, under the effect of the addition of ferrous ion at 0, 50 and 150 M and zinc ion at 0 and 50 M. The strains showed inhibition on biomass and ethanol production under the effect of zinc and ferrous ions, however, this inhibition was greater in the presence of zinc or iron at high concentration. GG570-CIBI showed reduction in biomass production of 4 g/L and an ethanol production drop of 40 % in the treatment 150 M iron–50 M zinc (with respect to the basal treatment). GG570-CIBII was the less affected with an inhibition on ethanol production below 11 % at 20 h of fermentation. Additionally, GG570-CIBII presented the greatest ethanol production when 150 M iron was added to the culture medium with or without zinc addition. In this case, the production was 9 and 14 % greater than ethanol production of CBS8066 and GG570-CIBI respectively, at the same conditions. Later, GG570-CIBII will be evaluated in industrial substrates due to its lower ethanol production inhibition, allowing for obtaining better yields.

The Effects of Divalant Cation on the Idarubicin-Induced Apoptosis / 대한소아혈액종양학회지

PURPOSE: Zinc ion is critical for the functional and structural integrity of eukaryotic cells and participate in the regulation of apoptosis. In general, zinc inhibits a nuclear endonuclease, thereby causing inhibition of apoptosis. Recent studies have pointed to a role for a family of caspase proteases that act upstream of endonuclease. The widely used chemotherapeutic agents exert effects by inducing of apoptosis in sensitive tumor cells. In this study, we investigated the effects of zinc ion and other divalent cation on the idarubicin (IDA)-induced apoptosis of HL-60 cells. In addition, to determine whether Zn inhibits an event upstream of endonuclease activation, we analysed the activity of caspase-3, 9 and proteolytic cleavage of procaspase-3 and PARP [poly (ADP-ribose) polymerase]. METHODS: HL-60 cells were cultured in RPMI 1640 and treated with various doses and time periods of IDA with or without pretreatment of ZnCl2, CaCl2 and MgCl2. Cell viability was measured by trypan blue staining. For detection of apoptotic death, cells were stained with Hoechst dye and observed under fluorescence microscopy. The activities of caspase-3 and caspase-9 were measured by the proteolytic cleavages of Ac- DEVD-AMC and Ac-LEHD-AFC as flurogenic substrates, respectively. The proteolytic cleavages of procaspase-3 and PARP were analyzed by Western blotting using anti- caspase-3 and anti-PARP antibody, respectively. RESULTS: IDA induced the apoptotic death of HL-60 cells in a dose and time dependent manner, which was characterized by increasing chromatin condensation and DNA fragmentation. Pretreatment of HL-60 cells with ZnCl2 caused potent inhibition of IDA-induced apoptosis. Consistent with apoptotic death of HL-60 cells, IDA induced the catalytic activation of caspase-3 and caspase-9. After pretreatment of ZnCl2, the activation of caspase- 3 and the proteolysis of PARP induced by IDA were potently inhibited. But, after pretreatment of CaCl2 and MgCl2, there were no significant changes of IDA-induced apoptosis and proteases activity. CONCLUSION: Zinc ion suppressed the IDA-induced apoptosis via the inhibitions of caspase-9 and caspase-3. But calcium and magnesium ions didn't affect the IDA-induced apoptosis.

The Effects of Zinc Ion on the Adriamycin-Induced Apoptosis of HL-60 Cells / 대한소아혈액종양학회지

PURPOSE: The widely used chemotherapeutic agents exert their anti-cancer effects by the inducing of apoptosis in sensitive tumor cells. Recently, the protective effect of zinc ion on apoptosis has been reproted. However, it is not well understood about the effects of zinc ion on the anticancer drug-induced apoptosis. In general, zinc inhibits a nuclear endonuclease, thereby causing inhibition of apoptosis. In addition, there is other possibility that zinc can prevent apoptosis at earlier stage such as the activation of caspase-3 than that of the activation of endonuclease. Therefore, we investigated the effects of zinc ion on the apoptosis of HL-60 cells caused by adriamycin (ADR). METHODS: HL-60 cells were cultured in RPMI 1640 and treated with various concentrations and time periods of ADR with or without pretreatment of zinc ion. Cellular DNA was extracted and analyzed by electrophoresis on a 1.5% agarose gel to detect DNA fragmentation. The activity of caspase-3 was measured by the proteolytic cleavage of the fluorogenic substrate DEVD-AMC. Poly-ADP-ribose polymerase (PARP) cleavage was analyzed by western blotting using anti-PARP antibody. RESULTS: ADR induced the apoptotic death of HL-60 cells in a dose and time dependent manner, which was characterized by increasing ladder-pattern DNA fragmentation. Pretreatment of HL-60 cells with zinc ion caused potent inhibition of ADR-induced apoptosis. Consistent with apoptotic death of HL-60 cells, ADR induced the catalytic activation of caspase-3. After pretreatment of zinc ion, the activation of caspase-3 and the proteolysis of PARP induced by ADR were markedly inhibited. CONCLUSION: These results indicate that zinc ion prevents the ADR-induced apoptosis of HL-60 cells through an inhibition of caspase-3 activity, which occurs upstream from the activation of endonuclease.

Effect of Intracellular ATP on Zn2+ Blockade of KATP Channels in Pancreatic Beta Cells

In the therapeutic or the nutritional aspects, Zn2+ has been used as a supplement in a variety of drugs. Most of divalent or trivalent cations affect ion channels in the cell membranes of various organs. In particular, Zn2+ has been regarded as a potassium (K+) channel blocker in the field of electrophysiology. ATP-sensitive K+ (KATP) channel, which is a kind of inward rectifier K+ channel, resides in the cell membrane of pancreatic beta cells and plays an important role in glucose-induced insulin secretion. The glucose increases intracellular ATP concentration, and this inhibits KATP channels. The inhibition of KATP channels activity depolarizes the cell, and subsequently, insulin is released by Ca2+ influx through the voltage- gated Ca2+ channels. Here, we demonstrate that KATP channels in the pancreatic beta cells are also the targets of extracellular Zn2+ blockade and its blockade is dependent on intracellular ATP concentration. This may be a compensatory mechanism preventing the oversecretion of insulin from the Pancreatic beta cells triggered by Zn2+ intake in a physiologically fasting condition.