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17 pages, 3330 KiB  
Article
Effect of Modified Bioceramic Mineral Trioxide Aggregate Cement with Mesoporous Nanoparticles on Human Gingival Fibroblasts
by Alexandra Kalash, Ioannis Tsamesidis, Georgia K. Pouroutzidou, Eleana Kontonasaki, Dimitrios Gkiliopoulos, Aristidis Arhakis, Konstantinos N. Arapostathis and Anna Theocharidou
Curr. Issues Mol. Biol. 2024, 46(4), 3005-3021; https://doi.org/10.3390/cimb46040188 - 30 Mar 2024
Viewed by 766
Abstract
The ion doping of mesoporous silica nanoparticles (MSNs) has played an important role in revolutionizing several materials applied in medicine and dentistry by enhancing their antibacterial and regenerative properties. Mineral trioxide aggregate (MTA) is a dental material widely used in vital pulp therapies [...] Read more.
The ion doping of mesoporous silica nanoparticles (MSNs) has played an important role in revolutionizing several materials applied in medicine and dentistry by enhancing their antibacterial and regenerative properties. Mineral trioxide aggregate (MTA) is a dental material widely used in vital pulp therapies with high success rates. The aim of this study was to investigate the effect of the modification of MTA with cerium (Ce)- or calcium (Ca)-doped MSNs on the biological behavior of human gingival fibroblasts (hGFs). MSNs were synthesized via sol–gel, doped with Ce and Ca ions, and mixed with MTA at three ratios each. Powder specimens were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Biocompatibility was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay following hGFs’ incubation in serial dilutions of material eluates. Antioxidant status was evaluated using Cayman’s antioxidant assay after incubating hGFs with material disc specimens, and cell attachment following dehydration fixation was observed through SEM. Material characterization confirmed the presence of mesoporous structures. Biological behavior and antioxidant capacity were enhanced in all cases with a statistically significant increase in CeMTA 50.50. The application of modified MTA with cerium-doped MSNs offers a promising strategy for vital pulp therapies. Full article
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25 pages, 7053 KiB  
Article
Strontium and Zinc Co-Doped Mesoporous Bioactive Glass Nanoparticles for Potential Use in Bone Tissue Engineering Applications
by Parichart Naruphontjirakul, Meng Li and Aldo R. Boccaccini
Nanomaterials 2024, 14(7), 575; https://doi.org/10.3390/nano14070575 - 26 Mar 2024
Cited by 1 | Viewed by 1132
Abstract
Mesoporous bioactive glass nanoparticles (MBGNs) have attracted significant attention as multifunctional nanocarriers for various applications in both hard and soft tissue engineering. In this study, multifunctional strontium (Sr)- and zinc (Zn)-containing MBGNs were successfully synthesized via the microemulsion-assisted sol–gel method combined with a [...] Read more.
Mesoporous bioactive glass nanoparticles (MBGNs) have attracted significant attention as multifunctional nanocarriers for various applications in both hard and soft tissue engineering. In this study, multifunctional strontium (Sr)- and zinc (Zn)-containing MBGNs were successfully synthesized via the microemulsion-assisted sol–gel method combined with a cationic surfactant (cetyltrimethylammonium bromide, CTAB). Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs exhibited spherical shapes in the nanoscale range of 100 ± 20 nm with a mesoporous structure. Sr and Zn were co-substituted in MBGNs (60SiO2-40CaO) to induce osteogenic potential and antibacterial properties without altering their size, morphology, negative surface charge, amorphous nature, mesoporous structure, and pore size. The synthesized MBGNs facilitated bioactivity by promoting the formation of an apatite-like layer on the surface of the particles after immersion in Simulated Body Fluid (SBF). The effect of the particles on the metabolic activity of human mesenchymal stem cells was concentration-dependent. The hMSCs exposed to Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs at 200 μg/mL enhanced calcium deposition and osteogenic differentiation without osteogenic supplements. Moreover, the cellular uptake and internalization of Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs in hMSCs were observed. These novel particles, which exhibited multiple functionalities, including promoting bone regeneration, delivering therapeutic ions intracellularly, and inhibiting the growth of Staphylococcus aureus and Escherichia coli, are potential nanocarriers for bone regeneration applications. Full article
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18 pages, 3493 KiB  
Article
In Silico Evaluation of Quercetin Methylated Derivatives on the Interaction with Secretory Phospholipases A2 from Crotalus durissus terrificus and Bothrops jararacussu
by Mariana Novo Belchor, Caroline Ramos da Cruz Costa, Airam Roggero, Laila L. F. Moraes, Ricardo Samelo, Isabelly Annunciato, Marcos Antonio de Oliveira, Sergio F. Sousa and Marcos Hikari Toyama
Pharmaceuticals 2023, 16(4), 597; https://doi.org/10.3390/ph16040597 - 15 Apr 2023
Cited by 2 | Viewed by 1428
Abstract
Quercetin derivatives have already shown their anti-inflammatory potential, inhibiting essential enzymes involved in this process. Among diverse pro-inflammatory toxins from snake venoms, phospholipase A2 is one of the most abundant in some species, such as Crotalus durissus terrificus and Bothrops jararacussu from the [...] Read more.
Quercetin derivatives have already shown their anti-inflammatory potential, inhibiting essential enzymes involved in this process. Among diverse pro-inflammatory toxins from snake venoms, phospholipase A2 is one of the most abundant in some species, such as Crotalus durissus terrificus and Bothrops jararacussu from the Viperidae family. These enzymes can induce the inflammatory process through hydrolysis at the sn-2 position of glycerophospholipids. Hence, elucidating the main residues involved in the biological effects of these macromolecules can help to identify potential compounds with inhibitory activity. In silico tools were used in this study to evaluate the potential of quercetin methylated derivatives in the inhibition of bothropstoxin I (BthTX-I) and II (BthTX-II) from Bothrops jararacussu and phospholipase A2 from Crotalus durissus terrificus. The use of a transitional analogous and two classical inhibitors of phospholipase A2 guided this work to find the role of residues involved in the phospholipid anchoring and the subsequent development of the inflammatory process. First, main cavities were studied, revealing the best regions to be inhibited by a compound. Focusing on these regions, molecular docking assays were made to show main interactions between each compound. Results reveal that analogue and inhibitors, Varespladib (Var) and p-bromophenacyl bromide (BPB), guided quercetins derivatives analysis, revealing that Leu2, Phe5, Tyr28, glycine in the calcium-binding loop, His48, Asp49 of BthTX-II and Cdtspla2 were the main residues to be inhibited. 3MQ exhibited great interaction with the active site, similar to Var results, while Q anchored better in the BthTX-II active site. However, strong interactions in the C-terminal region, highlighting His120, seem to be crucial to decreasing contacts with phospholipid and BthTX-II. Hence, quercetin derivatives anchor differently with each toxin and further in vitro and in vivo studies are essential to elucidate these data. Full article
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15 pages, 3648 KiB  
Article
Studies on Pollen Morphology, Pollen Vitality and Preservation Methods of Gleditsia sinensis Lam. (Fabaceae)
by Qiao Liu, Ju Yang, Xiurong Wang and Yang Zhao
Forests 2023, 14(2), 243; https://doi.org/10.3390/f14020243 - 28 Jan 2023
Cited by 8 | Viewed by 5373
Abstract
Gleditsia sinensis Lam. (Fabaceae) is an endemic species in China, which has a wide range of ecological functions and high economic value. G. sinensis belongs to androdioecy, and the stamens of perfect flowers are aborted, meaning that a perfect flower is a functional [...] Read more.
Gleditsia sinensis Lam. (Fabaceae) is an endemic species in China, which has a wide range of ecological functions and high economic value. G. sinensis belongs to androdioecy, and the stamens of perfect flowers are aborted, meaning that a perfect flower is a functional female flower. Understanding the dynamic process of flowering and the characteristics of pollen morphology effectively determine the viability of pollen vitality, and the suitable conditions for short-term storage of pollen can provide theoretical basis and technical reference for hybrid breeding and germplasm conservation of G. sinensis. In this study, the male plants of G. sinensis in Guiyang area were used as research materials. The flowering dynamic process of male flowers was recorded through field observation. The morphology of pollen was observed and analyzed with a scanning electron microscope (SEM). The germination characteristics of pollen were studied with an in vitro germination method, and the pollen vitality was also determined using four staining methods. The effects of different storage temperatures and water contents on pollen germination rate were discussed. The results showed that the male flowers of G. sinensis had a short, single flowering period, lasting 2–3 days from the opening to the shedding. The dynamic opening process of a single flower was artificially divided into five stages. Pollen grains of G. sinensis are oblate spheroidal, tricolporate with equatorial elongated endoapertures and the sporoderm surface is reticulate. The MTT (Thiazolyl Blue Tetrazolium Bromide) staining method could accurately and quickly determine the pollen vitality of G. sinensis. The highest pollen germination rate was 65.89% ± 3.41%, and the length of the pollen tube was 3.96 mm after cultured in 15% sucrose + 100 mg/L boric acid + 20 mg/L calcium chloride for 24 h. It was necessary to collect the pollen at the big bud stage, which was conducive to improving the efficiency of pollen collection because the pollen had been mature with high pollen vitality at this stage. When it came to pollen preservation, the pollen germination rate was significantly affected by storage time, storage temperature and pollen water content. The pollen still had high vitality after being stored at −80 °C for 30 days when the moisture content of the pollen decreased to 9%, and the pollen germination rate only decreased by 28.84% compared with that before storage. In conclusion, this study has comprehensively and systematically studied the morphology, vitality determination and preservation methods of the pollen of G. sinensis, providing a theoretical basis for the cross regional breeding and the conservation and utilization of germplasm resources. Full article
(This article belongs to the Special Issue Biodiversity and Conservation of Forests)
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18 pages, 3366 KiB  
Article
The Lebanese Red Algae Jania rubens: Promising Biomolecules against Colon Cancer Cells
by Mariam Rifi, Zeina Radwan, Reem AlMonla, Ziad Fajloun, Jean Marc Sabatier, Achraf Kouzayha, Marwan El-Sabban, Hiba Mawlawi and Zeina Dassouki
Molecules 2022, 27(19), 6617; https://doi.org/10.3390/molecules27196617 - 5 Oct 2022
Cited by 2 | Viewed by 2716
Abstract
Colorectal cancer (CRC) is ranked the second most lethal type of tumor globally. Thus, developing novel anti-cancer therapeutics that are less aggressive and more potent is needed. Recently, natural bioactive molecules are gaining interest as complementary and supportive antineoplastic treatments due to their [...] Read more.
Colorectal cancer (CRC) is ranked the second most lethal type of tumor globally. Thus, developing novel anti-cancer therapeutics that are less aggressive and more potent is needed. Recently, natural bioactive molecules are gaining interest as complementary and supportive antineoplastic treatments due to their safety, effectiveness, and low cost. Jania rubens (J. rubens) is a red coral seaweed abundant in the Mediterranean and bears a significant pharmacological essence. Despite its therapeutic potential, the natural biomolecules extracted from this alga are poorly identified. In this study, the proximal analysis revealed high levels of total ash content (66%), 11.3% proteins, 14.5% carbohydrates, and only 4.5% lipids. The elemental identification showed magnesium and calcium were high among its macro minerals, (24 ± 0.5 mg/g) and (33 ± 0.5 mg/g), respectively. The Chlorophyll of J. rubens was dominated by other pigments with (0.82 ± 0.02 mg/g). A 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay identified effective antioxidant activity in various J. rubens extracts. More importantly, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium reduction and wound healing assays indicate that organic extracts from J. rubens significantly counteract the proliferation of colon cancer cell lines (HCT-116 and HT-29) and inhibit their migratory and metastatic properties in a dose and time-dependent manner. Overall, this study provides insight into the physicochemical properties of red seaweed, J. rubens, and identifies its significant antioxidant, cytotoxic, and anti-migratory potential on two colorectal cell lines, HCT-116 and HT-29. Full article
(This article belongs to the Special Issue Anticancer Drug Discovery and Development II)
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17 pages, 3348 KiB  
Article
Sodium Alginate/Modified Bentonite Composite Bead Adsorptive Removal of Norfloxacin: Static and Dynamic Adsorption
by Jun Zhou and Qianyu Sun
Polymers 2022, 14(19), 3984; https://doi.org/10.3390/polym14193984 - 23 Sep 2022
Cited by 8 | Viewed by 1879
Abstract
The low-cost calcium-based bentonite modified with anionic and cationic surfactants was granulated by cross-linking to sodium alginate (SA) to promote the adsorption efficiencies of norfloxacin (NOR). The characterization studies illustrated that the intercalation of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl benzene sulfonate (SDBS) [...] Read more.
The low-cost calcium-based bentonite modified with anionic and cationic surfactants was granulated by cross-linking to sodium alginate (SA) to promote the adsorption efficiencies of norfloxacin (NOR). The characterization studies illustrated that the intercalation of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl benzene sulfonate (SDBS) was successful. The modification improved the pore structure and the granular SA/organically modified bentonite composite (GOMBt) exhibited a lamellar structure with some roughness. The adsorption kinetics and isotherms indicated that adsorption of NOR on GOMBt was an endothermic process. The effects of various factors on the adsorption of NOR suggested that the maximum adsorption capacity was obtained under acidic conditions and cations improved the adsorption process. A fixed-bed column was employed to investigate the dynamic adsorption characteristics of NOR by GOMBt. The breakthrough time and bed height had a positive correlation; however, the relation of flow rate, pH, and breakthrough time had a negative correlation. The results showed that the dynamic adsorption data of NOR on GOMBt fitted Thomas and Yoon–Nelson models. The internal and external diffusion in GOMBt dynamic adsorption was not a rate-limiting step. Full article
(This article belongs to the Special Issue Polymeric Materials for Water/Wastewater Treatment Applications)
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13 pages, 3226 KiB  
Article
Insignificant Difference in Biocompatibility of Regenerated Silk Fibroin Prepared with Ternary Reagent Compared with Regenerated Silk Fibroin Prepared with Lithium Bromide
by Guotao Cheng, Xin Wang, Mengqiu Wu, Siyuan Wu, Lan Cheng, Xiaoning Zhang and Fangyin Dai
Polymers 2022, 14(18), 3903; https://doi.org/10.3390/polym14183903 - 18 Sep 2022
Cited by 6 | Viewed by 3153
Abstract
Bombyx mori silk fibroin (SF) is widely used in the field of biomaterials due to its excellent biocompatibility and mechanical properties. However, SF cannot be used directly in many applications and needs to be dissolved first. Lithium bromide (LiBr) is a traditional solvent [...] Read more.
Bombyx mori silk fibroin (SF) is widely used in the field of biomaterials due to its excellent biocompatibility and mechanical properties. However, SF cannot be used directly in many applications and needs to be dissolved first. Lithium bromide (LiBr) is a traditional solvent which is usually used to dissolve SF. However, LiBr has several limitations, e.g., it is expensive, it is toxic to organisms, and it is environmentally unfriendly. Herein, we investigate the possibility of developing a ternary reagent system that is inexpensive, non-toxic to organisms, and environmentally friendly as an alternative for silk fibroin solubilization. The results confirm that regenerated silk fibroin (RSF) prepared using a ternary reagent has the same morphology and amino acid composition as that prepared using LiBr, but the RSF prepared using a ternary reagent still had a small amount of calcium residue even after long-term dialysis. Further research found that the residual calcium does not cause significant differences in the structure and biological performance of the RSF, such as its cytotoxicity, blood compatibility, and antibacterial properties. Therefore, we believe that ternary reagents are an ideal alternative solvent for dissolving SF. Full article
(This article belongs to the Special Issue Advances in Fiber Materials and Manufacturing)
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14 pages, 2445 KiB  
Article
Biological Activities of Glass Ionomer Cement Supplemented with Fortilin on Human Dental Pulp Stem Cells
by Prawichaya Sangsuwan, Sissada Tannukit, Wilaiwan Chotigeat and Ureporn Kedjarune-Leggat
J. Funct. Biomater. 2022, 13(3), 132; https://doi.org/10.3390/jfb13030132 - 28 Aug 2022
Cited by 3 | Viewed by 1744
Abstract
This study aimed to determine the most suitable recombinant fortilin and evaluate the biological activities of glass ionomer cement (GIC) incorporated with fortilin on human dental pulp stem cells (hDPSCs). Full-length and three fragments of Penaeus merguiensis fortilin were cloned and examined for [...] Read more.
This study aimed to determine the most suitable recombinant fortilin and evaluate the biological activities of glass ionomer cement (GIC) incorporated with fortilin on human dental pulp stem cells (hDPSCs). Full-length and three fragments of Penaeus merguiensis fortilin were cloned and examined for their proliferative and cytoprotective effects on hDPSCs by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Human DPSCs were cultured with GIC supplemented with fortilin, tricalcium phosphate, or a combination of tricalcium phosphate and fortilin, designated as GIC + FL, GIC + TCP, and GIC + TCP + FL, respectively (n = 4 for each group). At given time points, hDPSCs were harvested and analyzed by MTT, quantitative reverse transcription polymerase chain reaction, alkaline phosphatase activity, and Alizarin Red assays. The full-length fortilin promoted cell proliferation and significantly increased cell survival. This protein was subsequently added into the GIC along with tricalcium phosphate to investigate the biological activities. All experimental groups showed reduced cell viability after treatment with modified GICs on days 1 and 3. The GIC + TCP + FL group significantly promoted odontoblastic differentiation at particular time points. In addition, alkaline phosphatase activity and calcium phosphate deposit were markedly increased in the GIC + TCP + FL group. Among all experimental groups, the GIC incorporated with fortilin and tricalcium phosphate demonstrated the best results on odontogenic differentiation and mineral deposition in hDPSCs. Full article
(This article belongs to the Special Issue Feature Papers in Dental Biomaterials)
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18 pages, 7604 KiB  
Article
Analysis and Experimental Study on Water Vapor Partial Pressure in the Membrane Distillation Process
by Zanshe Wang, Zhaoying Jia, Ran Li, Qi Gao and Zhaolin Gu
Membranes 2022, 12(8), 802; https://doi.org/10.3390/membranes12080802 - 19 Aug 2022
Cited by 6 | Viewed by 2294
Abstract
In membrane distillation, the vapor pressure difference is the driving force of mass transfer. The vapor pressure is generally assumed by the saturation pressure and calculated by the Antoine equation. However, in the actual operation process, the feed solutions usually flow in a [...] Read more.
In membrane distillation, the vapor pressure difference is the driving force of mass transfer. The vapor pressure is generally assumed by the saturation pressure and calculated by the Antoine equation. However, in the actual operation process, the feed solutions usually flow in a non-equilibrium state, which does not meet the theoretical and measurement conditions of the vapor-liquid equilibrium (VLE) state. This study tested the actual water vapor pressure of the pure water, lithium bromide (LiBr) solution, lithium chloride (LiCl) solution, and calcium chloride (CaCl2) solution under different flow conditions. The results showed that the actual water vapor pressure was lower than the saturation pressure overall, and the difference increased with temperature but decreased with the mass concentration. Therefore, in vacuum membrane distillation (VMD), air gap membrane distillation (AGMD), and sweeping gas membrane distillation (SGMD), the membrane flux calculated by water vapor saturation pressure was higher than the actual membrane flux, and the relative difference decreased and was less than 10% after 60 °C. In direct contact membrane distillation (DCMD), the water vapor pressure difference on both membrane sides was almost the same by using the saturation vapor pressure or the tested data since the pressure errors were partially offset in parallel flow or counter-flow modes. Full article
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15 pages, 4636 KiB  
Article
Surface Modification of Synthetic Zeolites with Ca and HDTMA Compounds with Determination of Their Phytoavailability and Comparison of CEC and AEC Parameters
by Michał Łach, Agnieszka Grela, Kinga Pławecka, Martin Duarte Guigou, Janusz Mikuła, Norbert Komar, Tomasz Bajda and Kinga Korniejenko
Materials 2022, 15(12), 4083; https://doi.org/10.3390/ma15124083 - 8 Jun 2022
Cited by 9 | Viewed by 1874
Abstract
Zeolites obtained from fly ash are characterized by very good anion- and cation-exchange properties and a developed porous structure. This paper presents the results of surface modification studies of synthetic zeolites obtained from calcined coal shale (clay materials). Calcium compounds and hexadecyltrimethylammonium bromide [...] Read more.
Zeolites obtained from fly ash are characterized by very good anion- and cation-exchange properties and a developed porous structure. This paper presents the results of surface modification studies of synthetic zeolites obtained from calcined coal shale (clay materials). Calcium compounds and hexadecyltrimethylammonium bromide (HDTMA) were used as modifying substances. The characteristics of the raw material and the zeolite obtained as a result of its synthesis are presented. The surface modification method is described. Furthermore, the results of sorption and desorption of NO3, PO4, and SO4 from raw and modified samples are presented. The results of anion- and cation-exchange capacities for other zeolite types were also compared. Modification of the materials with Ca ions and HDTMA surfactant only improved the sorption of sulfates. The 90% desorption of nitrates, phosphates, and sulphates from the zeolite material without modification indicates a good release capacity of these compounds and their potential use as fertilizer additives. Full article
(This article belongs to the Special Issue Zeolitic Materials: Structure, Properties, and Applications)
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14 pages, 3495 KiB  
Article
The Effects of Polyphenol, Tannic Acid, or Tannic Acid in Combination with Pamidronate on Human Osteoblast Cell Line Metabolism
by Hermizi Hapidin, Nor Munira Hashim, Mohamad Zahid Kasiram and Hasmah Abdullah
Molecules 2022, 27(2), 451; https://doi.org/10.3390/molecules27020451 - 11 Jan 2022
Cited by 5 | Viewed by 2102
Abstract
Background: This study investigates the effect of tannic acid (TA) combined with pamidronate (PAM) on a human osteoblast cell line. Methods: EC50 for TA, PAM, and different combination ratios of TA and PAM (25:75, 50:50, 75:25) were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) [...] Read more.
Background: This study investigates the effect of tannic acid (TA) combined with pamidronate (PAM) on a human osteoblast cell line. Methods: EC50 for TA, PAM, and different combination ratios of TA and PAM (25:75, 50:50, 75:25) were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The combination index value was utilized to analyze the degree of drug interaction, while trypan blue assay was applied to analyze the cells proliferation effect. The mineralization and detection of bone BSP and Osx genes were determined via histochemical staining and PCR test, respectively. Results: The EC50 of osteoblasts treated with TA and a 75:25 ratio of TA and PAM were more potent with lower EC50 at 0.56 µg/mL and 0.48 µg/mL, respectively. The combination of TA and PAM (75:25) was shown to have synergistic interaction. On Day 7, both TA and PAM groups showed significantly increased proliferation compared with control and combination groups. On Day 7, both the TA and combination-treated groups demonstrated a higher production of calcium deposits than the control and PAM-treated groups. Moreover, on Day 7, the combination-treated group showed a significantly higher expression of BSP and Osx genes than both the TA and PAM groups. Conclusion: Combination treatment of TA and PAM at 75:25 ameliorated the highest enhancement of osteoblast proliferation and mineralization as well as caused a high expression of BSP and Osx genes. Full article
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6 pages, 989 KiB  
Proceeding Paper
Effective Synthesis of a Novel Betulinic Acid Conjugate with Mitochondria-Targeting Cation F16
by Darya Nedopekina, Eldar Davletshin and Anna Spivak
Chem. Proc. 2022, 8(1), 97; https://doi.org/10.3390/ecsoc-25-11638 - 12 Nov 2021
Viewed by 1030
Abstract
Currently, mitochondria are considered as an attractive universal target in the development of new anticancer drugs. These organelles are essential in energy production, the regulation of cell death pathways, the generation of reactive oxygen species, as well as in the maintenance of calcium [...] Read more.
Currently, mitochondria are considered as an attractive universal target in the development of new anticancer drugs. These organelles are essential in energy production, the regulation of cell death pathways, the generation of reactive oxygen species, as well as in the maintenance of calcium homeostasis. Various approaches are being developed to deliver biologically active compounds into the mitochondria of tumour cells, including the conjugation of cytotoxic substances with mitochondria-targeted lipophilic cations. Among the currently known low molecular weight lipophilic cationic molecules, (E)-4(1H-indol-3-ylvinyl)-N-methylpyridinium iodide (F16) is of great interest. This mitochondria-toxic cationic compound with luminescent properties is selectively accumulated in mitochondria and can selectively trigger the apoptosis and necrosis of tumour cells, making it an attractive targeted agent for theranostic use. Meanwhile, betulinic acid, an available natural pentacyclic triterpenoid, has been considered as a promising scaffold for the development of new anticancer agents in recent years. The antitumour effect of this natural product arises from it affecting the mitochondria of tumour cells through the formation of reactive oxygen species. The present article details of an efficient synthesis of a novel multifunctional hybrid agent in which a cytotoxic triterpenoid, betulinic acid, is carbon-carbon bonded to the cationic F16 fragment at the C-2 position of ring A through a phenylethynyl spacer. The starting substrates in the synthesis were the C-2 propynyl derivative of betulinic acid and N-aryl-substituted 4-(1H-indol-3-ylvinyl)-pyridine. The derivative of betulinic acid with a terminal acetylenic group was prepared by the reaction of C-alkylation with propargyl bromide of potassium enoxytriethylborate generated from betulonic acid. To obtain the N-aryl-substituted analogue of F16, a CuI-catalyzed Ullmann-Goldberg reaction was applied. The synthesis of the target conjugate was successfully completed by the cross-coupling of the terpene and heterocyclic components according to Sonogashira in the presence of the CuI/Pd(PPh3)2 catalyst. Full article
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20 pages, 51802 KiB  
Article
Synthesis and Toxicity Evaluation of New Pyrroles Obtained by the Reaction of Activated Alkynes with 1-Methyl-3-(cyanomethyl)benzimidazolium Bromide
by Beatrice-Cristina Ivan, Florea Dumitrascu, Adriana Iuliana Anghel, Robert Viorel Ancuceanu, Sergiu Shova, Denisa Dumitrescu, Constantin Draghici, Octavian Tudorel Olaru, George Mihai Nitulescu, Mihaela Dinu and Stefania-Felicia Barbuceanu
Molecules 2021, 26(21), 6435; https://doi.org/10.3390/molecules26216435 - 25 Oct 2021
Cited by 4 | Viewed by 2397
Abstract
A series of new pyrrole derivatives were designed as chemical analogs of the 1,4-dihydropyridines drugs in order to develop future new calcium channel blockers. The new tri- and tetra-substituted N-arylpyrroles were synthesized by the one-pot reaction of 1-methyl-3-cyanomethyl benzimidazolium bromide with substituted [...] Read more.
A series of new pyrrole derivatives were designed as chemical analogs of the 1,4-dihydropyridines drugs in order to develop future new calcium channel blockers. The new tri- and tetra-substituted N-arylpyrroles were synthesized by the one-pot reaction of 1-methyl-3-cyanomethyl benzimidazolium bromide with substituted alkynes having at least one electron-withdrawing substituent, in 1,2-epoxybutane, acting both as the solvent and reagent to generate the corresponding benzimidazolium N3-ylide. The structural characterization of the new substituted pyrroles was based on IR, NMR spectroscopy as well as on single crystal X-ray analysis. The toxicity of the new compounds was assessed on the plant cell using Triticum aestivum L. species and on the animal cell using Artemia franciscana Kellogg and Daphnia magna Straus crustaceans. The compounds showed minimal phytotoxicity on Triticum rootlets and virtually no acute toxicity on Artemia nauplii, while on Daphnia magna, it induced moderate to high toxicity, similar to nifedipine. Our research indicates that the newly synthetized pyrrole derivatives are promising molecules with biological activity and low acute toxicity. Full article
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14 pages, 5544 KiB  
Article
Combination of Selective Etching and Impregnation toward Hollow Mesoporous Bioactive Glass Nanoparticles
by Nurshen Mutlu, Ana Maria Beltrán, Qaisar Nawaz, Martin Michálek, Aldo R. Boccaccini and Kai Zheng
Nanomaterials 2021, 11(7), 1846; https://doi.org/10.3390/nano11071846 - 16 Jul 2021
Cited by 11 | Viewed by 3286
Abstract
In this study, binary SiO2-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO2 NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed [...] Read more.
In this study, binary SiO2-CaO hollow mesoporous bioactive glass nanoparticles (HMBGNs) are prepared by combing selective etching and impregnation strategies. Spherical silica particles (SiO2 NPs) are used as hard cores to assemble cetyltrimethylammonium bromide (CTAB)/silica shells, which are later removed by selective etching to generate a hollow structure. After the removal of CTAB by calcination, the mesoporous shell of particles is formed. Calcium (Ca) is incorporated into the particles using impregnation by soaking the etched SiO2 NPs in calcium nitrate aqueous solution. The amount of incorporated Ca is tailorable by controlling the ratio of SiO2 NPs:calcium nitrate in the soaking solution. The produced HMBGNs are bioactive, as indicated by the rapid formation of hydroxyapatite on their surfaces after immersion in simulated body fluid. In a direct culture with MC3T3-E1 cells, HMBGNs were shown to exhibit concentration-dependent cytotoxicity and can stimulate osteogenic differentiation of MC3T3-E1 cells at concentrations of 1, 0.5, and 0.25 mg/mL. Our results indicate that the combination of selective etching and impregnation is a feasible approach to produce hierarchical HMBGNs. The produced hollow particles have potential in drug delivery and bone tissue regeneration applications, and should be further investigated in detailed in vitro and in vivo studies. Full article
(This article belongs to the Special Issue Nanoparticles for Bio-Medical Applications)
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20 pages, 6279 KiB  
Article
Effects of Ti6Al4V Surfaces Manufactured through Precision Centrifugal Casting and Modified by Calcium and Phosphorus Ion Implantation on Human Osteoblasts
by Fiedler Jörg, Katmer Amet Betül, Michels Heiner, Kappelt Gerhard and Brenner Rolf Erwin
Metals 2020, 10(12), 1681; https://doi.org/10.3390/met10121681 - 16 Dec 2020
Cited by 5 | Viewed by 2399
Abstract
(1) In order to enable a more widespread use of uncemented titanium-based endoprostheses to replace cobalt-containing cemented endoprostheses for joint replacement, it is essential to achieve optimal osseointegrative properties and develop economic fabrication processes while retaining the highest biomedical quality of titanium materials. [...] Read more.
(1) In order to enable a more widespread use of uncemented titanium-based endoprostheses to replace cobalt-containing cemented endoprostheses for joint replacement, it is essential to achieve optimal osseointegrative properties and develop economic fabrication processes while retaining the highest biomedical quality of titanium materials. One approach is the usage of an optimized form of Ti6Al4V-precision casting for manufacturing. Besides the chemical and physical properties, it is necessary to investigate possible biological influences in order to test whether the new manufacturing process is equivalent to conventional methods. (2) Methods: Primary human osteoblasts were seeded on discs, which were produced by a novel Ti6Al4V centrifugal-casting process in comparison with standard machined discs of the same titanium alloy. In a second step, the surfaces were modified by calcium or phosphorus ion beam implantation. In vitro, we analyzed the effects on proliferation, differentiation, and apoptotic processes. (3) Results: SEM analysis of cells seeded on the surfaces showed no obvious differences between the reference material and the cast material with or without ion implantation. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay also did not reveal any significant differences. Additionally, the osteogenic differentiation process tested by quantitative polymerase chain reactions (PCR), Alizarin red S assay, and C-terminal collagen type I propeptide (CICP) Elisa was not significantly modified. No signs of induced apoptosis were observed. (4) Conclusions: In this study, we could show that the newly developed process of centrifugal casting generated a material with comparable surface features to standard machined Ti6Al4V material. In terms of biological impact on primary human osteoblasts, no significant differences were recognized. Additional Ca- or P-ion implantation did not improve or impair these characteristics in the dosages applied. These findings indicate that spin casting of Ti6Al4V may represent an interesting alternative to the production of geometrically complex orthopedic implants. Full article
(This article belongs to the Special Issue Titanium and Its Alloys for Biomedical Applications)
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