Factors influencing the drug release from calcium phosphate cements
|
01.01.2022 |
Fosca M.
Rau J.V.
Uskoković V.
|
Bioactive Materials |
10.1016/j.bioactmat.2021.05.032 |
0 |
Ссылка
Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.
Читать
тезис
|
Factors influencing the drug release from calcium phosphate cements
|
01.01.2022 |
Fosca M.
Rau J.V.
Uskoković V.
|
Bioactive Materials |
10.1016/j.bioactmat.2021.05.032 |
0 |
Ссылка
Thanks to their biocompatibility, biodegradability, injectability and self-setting properties, calcium phosphate cements (CPCs) have been the most economical and effective biomaterials of choice for use as bone void fillers. They have also been extensively used as drug delivery carriers owing to their ability to provide for a steady release of various organic molecules aiding the regeneration of defective bone, including primarily antibiotics and growth factors. This review provides a systematic compilation of studies that reported on the controlled release of drugs from CPCs in the last 25 years. The chemical, compositional and microstructural characteristics of these systems through which the control of the release rates and mechanisms could be achieved have been discussed. In doing so, the effects of (i) the chemistry of the matrix, (ii) porosity, (iii) additives, (iv) drug types, (v) drug concentrations, (vi) drug loading methods and (vii) release media have been distinguished and discussed individually. Kinetic specificities of in vivo release of drugs from CPCs have been reviewed, too. Understanding the kinetic and mechanistic correlations between the CPC properties and the drug release is a prerequisite for the design of bone void fillers with drug release profiles precisely tailored to the application area and the clinical picture. The goal of this review has been to shed light on these fundamental correlations.
Читать
тезис
|
Tricalcium phosphate cement supplemented with boron nitride nanotubes with enhanced biological properties
|
01.09.2020 |
Rau J.V.
Fosca M.
Fadeeva I.V.
Kalay S.
Culha M.
Raucci M.G.
Fasolino I.
Ambrosio L.
Antoniac I.V.
Uskoković V.
|
Materials Science and Engineering C |
10.1016/j.msec.2020.111044 |
0 |
Ссылка
© 2020 Elsevier B.V. A self-setting bone cement containing β-tricalcium phosphate (TCP) supplemented with boron nitride nanotubes (BNNTs, 1 wt%) was synthesized and analyzed in situ for its kinetics of hardening and selected physicochemical and biological properties. Moderately delayed due to the presence of BNNTs, the hardening reaction involved the transformation of the TCP precursor to the dicalcium phosphate (DCPD) product. In spite of the short-lived chemical transformations in the cement upon its hardening, the structural changes in it were extended. As a result, the compressive strength increased from day 1 to day 7 of the hardening reaction and the presence of BNNTs further increased it by ~25%. Fitting of the time-resolved energy-dispersive diffractometric data to the Johnson-Mehl-Avrami-Kolmogorov crystallization kinetics model conformed to the one-dimensional nucleation at a variable rate during the growth of elongated DCPD crystals from round TCP grains. For the first seven days of growth of human mesenchymal stem cells (hMSCs) on the cement, no difference in their proliferation was observed compared to the control. However, between the 7th and the 21st day, the cell proliferation decreased compared to the control because of the ongoing stem cell differentiation toward the osteoblast phenotype. This differentiation was accompanied by the higher expression of alkaline phosphatase, an early marker of hMSC differentiation into a pre-osteoblast phenotype. The TCP cement supplemented with BNNTs was able to thwart the production of reactive oxygen species (ROS) in hMSCs treated with H2O2/Fe2+ and bring the ROS levels down to the concentrations detected in the control cells, indicating the good capability of the material to protect the cells against the ROS-associated damage. Simultaneously, the cement increased the expression of mediators of inflammation in a co-culture of osteoblasts and macrophages, thus attesting to the direct reciprocity between the degrees of inflammation and stimulated new bone production.
Читать
тезис
|
Influence of oblique angle deposition on Cu-substituted hydroxyapatite nano-roughness and morphology
|
25.07.2020 |
Prosolov K.A.
Khimich M.A.
Rau J.V.
Lychagin D.V.
Sharkeev Y.P.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2020.125883 |
0 |
Ссылка
© 2020 Elsevier B.V. In this work, we study the effect of RF magnetron oblique angle deposition (OAD) on morphology, structure, and elemental composition of as-deposited and heat-treated Cu containing calcium phosphates. The control over the surface morphology and nano roughness provided by OAD is of great interest as both Mesenchymal Stem Cells and various types of bacteria respond strongly to nanoscale topography. A Cu substituted hydroxyapatite target was used to deposit coatings on the surface of titanium (Ti) and silicon (Si) substrates. The samples were placed at an oblique angle of 80° relative to the surface of the sample holder and in a normal configuration with respect to the flux direction and, therefore, parallel to the target. The dense homogeneous coatings with globular surface features deposited at normal flux incidence (NFI) configuration changed to elliptical, highly oriented structures with the direction dictated by the atomic shadowing effect when the substrate was deposited at an oblique angle. As-deposited thin films were subjected to post-deposition-heat-treatment at 700 °C in an Ar atmosphere. This led to a drastic change in the surface morphology and, namely, lost the directionality of the nanostructures. According to the X-ray diffraction data, the samples deposited obliquely showed preferential growth in the (002) plane and lower internal stress, than samples coated at NFI for both the Si and Ti substrates. The RMS roughness of the films deposited obliquely on Si was twice that of the films deposited at NFI (860 ± 80 pm and 408 ± 60 pm, respectively). However, it was not the case for the Ti substrate, the RMS roughness decreased from 42 ± 4 nm for coatings deposited at normal flux geometry to 33 ± 2 nm for coatings deposited obliquely. The heat-treatment of the samples deposited at 80° resulted in a significant increase in the surface roughness: 8 ± 0.7 nm for Si and 71 ± 4 nm for Ti substrates. The obtained results demonstrate that the oblique angle deposition can be used to fabricate nano-rough surface morphologies.
Читать
тезис
|
Influence of oblique angle deposition on Cu-substituted hydroxyapatite nano-roughness and morphology
|
25.07.2020 |
Prosolov K.A.
Khimich M.A.
Rau J.V.
Lychagin D.V.
Sharkeev Y.P.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2020.125883 |
0 |
Ссылка
© 2020 Elsevier B.V. In this work, we study the effect of RF magnetron oblique angle deposition (OAD) on morphology, structure, and elemental composition of as-deposited and heat-treated Cu containing calcium phosphates. The control over the surface morphology and nano roughness provided by OAD is of great interest as both Mesenchymal Stem Cells and various types of bacteria respond strongly to nanoscale topography. A Cu substituted hydroxyapatite target was used to deposit coatings on the surface of titanium (Ti) and silicon (Si) substrates. The samples were placed at an oblique angle of 80° relative to the surface of the sample holder and in a normal configuration with respect to the flux direction and, therefore, parallel to the target. The dense homogeneous coatings with globular surface features deposited at normal flux incidence (NFI) configuration changed to elliptical, highly oriented structures with the direction dictated by the atomic shadowing effect when the substrate was deposited at an oblique angle. As-deposited thin films were subjected to post-deposition-heat-treatment at 700 °C in an Ar atmosphere. This led to a drastic change in the surface morphology and, namely, lost the directionality of the nanostructures. According to the X-ray diffraction data, the samples deposited obliquely showed preferential growth in the (002) plane and lower internal stress, than samples coated at NFI for both the Si and Ti substrates. The RMS roughness of the films deposited obliquely on Si was twice that of the films deposited at NFI (860 ± 80 pm and 408 ± 60 pm, respectively). However, it was not the case for the Ti substrate, the RMS roughness decreased from 42 ± 4 nm for coatings deposited at normal flux geometry to 33 ± 2 nm for coatings deposited obliquely. The heat-treatment of the samples deposited at 80° resulted in a significant increase in the surface roughness: 8 ± 0.7 nm for Si and 71 ± 4 nm for Ti substrates. The obtained results demonstrate that the oblique angle deposition can be used to fabricate nano-rough surface morphologies.
Читать
тезис
|
Lipid peroxidation is involved in calcium dependent upregulation of mitochondrial metabolism in skeletal muscle
|
01.03.2020 |
Al-Menhali A.
Banu S.
Angelova P.
Barcaru A.
Horvatovich P.
Abramov A.
Jaganjac M.
|
Biochimica et Biophysica Acta - General Subjects |
10.1016/j.bbagen.2019.129487 |
0 |
Ссылка
© 2019 Elsevier B.V. Background: Skeletal muscle cells continuously generate reactive oxygen species (ROS). Excessive ROS can affect lipids resulting in lipid peroxidation (LPO). Here we investigated the effects of myotube intracellular calcium-induced signaling eliciting contractions on the LPO induction and the impact of LPO-product 4-hydroxynonenal (4-HNE) on physiology/pathology of myotubes using C2C12 myoblasts. Methods: C2C12 myoblasts were differentiated into myotubes, stimulated with caffeine and analyzed for the induction of LPO and formation of 4-HNE protein adducts. Further effects of 4-HNE on mitochondrial bioenergetics, NADH level, mitochondrial density and expression of mitochondrial metabolism genes were determined. Results: Short and long-term caffeine stimulation of myotubes promoted superoxide production, LPO and formation of 4-HNE protein adducts. Furthermore, low 4-HNE concentrations had no effect on myotube viability and cellular redox homeostasis, while concentrations from 10 μM and above reduced myotube viability and significantly disrupted homeostasis. A time and dose-dependent 4-HNE effect on superoxide production and mitochondrial NADH-autofluorescence was observed. Finally, 4-HNE had strong impact on maximal respiration, spare respiratory capacity, ATP production, coupling efficiency of mitochondria and mitochondrial density. Conclusion: Data presented in this work make evident for the first time that pathological 4-HNE levels elicit damaging effects on skeletal muscle cells while acute exposure to physiological 4-HNE induces transient adaptation. General significance: This work suggests an important role of 4-HNE on the regulation of myotube's mitochondrial metabolism and cellular energy production. It further signifies the importance of skeletal muscle cells hormesis in response to acute stress in order to maintain essential biological functions.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
Octacalcium phosphate coating for 3D printed cranioplastic porous titanium implants
|
15.02.2020 |
Smirnov I.
Deev R.
Bozo I.
Fedotov A.
Gurin A.
Mamonov V.
Kravchuk A.
Popov V.
Egorov A.
Komlev V.
|
Surface and Coatings Technology |
10.1016/j.surfcoat.2019.125192 |
0 |
Ссылка
© 2019 Elsevier B.V. In the present study, porous three-dimensional (3D) printed titanium (Ti) implants of complex shape and predefined architecture were produced by selective laser sintering (SLS) technique. Electrochemical deposition combined with biomimetic approach was applied to low-temperature coating of these implants with metastable octacalcium phosphate (OCP) achieved via chemical transformation of dicalcium phosphate dehydrate (DCPD). X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and compressive strength analyses were applied to study the chemical composition, morphology and mechanical properties of the final OCP coating on the titanium surface. In vivo comparative study of the porous 3D printed Ti and OCP coated Ti implants has been performed using critical-size crania model, porous 3D printed Ti and coated implants were compared. A statistically significant difference in the newly formed bone thickness for OCP coated Ti implants was detected already at 6 weeks after implantation. Our results provide an experimental proof of a new concept of OCP coating for cranioplasty clinical applications.
Читать
тезис
|
In silico simulation of reversible and irreversible swelling of mitochondria: The role of membrane rigidity
|
01.01.2020 |
Makarov V.
Khmelinskii I.
Khuchua Z.
Javadov S.
|
Mitochondrion |
10.1016/j.mito.2019.09.006 |
0 |
Ссылка
© 2019 Elsevier B.V. and Mitochondria Research Society Mitochondria have been widely accepted as the main source of ATP in the cell. The inner mitochondrial membrane (IMM) is important for the maintenance of ATP production and other functions of mitochondria. The electron transport chain (ETC) generates an electrochemical gradient of protons known as the proton-motive force across the IMM and thus produces the mitochondrial membrane potential that is critical to ATP synthesis. One of the main factors regulating the structural and functional integrity of the IMM is the changes in the matrix volume. Mild (reversible) swelling regulates mitochondrial metabolism and function; however, excessive (irreversible) swelling causes mitochondrial dysfunction and cell death. The central mechanism of mitochondrial swelling includes the opening of non-selective channels known as permeability transition pores (PTPs) in the IMM by high mitochondrial Ca2+ and reactive oxygen species (ROS). The mechanisms of reversible and irreversible mitochondrial swelling and transition between these two states are still unknown. The present study elucidates an upgraded biophysical model of reversible and irreversible mitochondrial swelling dynamics. The model provides a description of the PTP regulation dynamics using an additional differential equation. The rigidity tensor was used in numerical simulations of the mitochondrial parameter dynamics with different initial conditions defined by Ca2+ concentration in the sarco/endoplasmic reticulum. We were able to estimate the values of the IMM rigidity tensor components by fitting the model to the previously reported experimental data. Overall, the model provides a better description of the reversible and irreversible mitochondrial swelling dynamics.
Читать
тезис
|
Loss of Orai2-Mediated Capacitative Ca<sup>2+</sup> Entry Is Neuroprotective in Acute Ischemic Stroke
|
01.11.2019 |
Stegner D.
Hofmann S.
Schuhmann M.
Kraft P.
Herrmann A.
Popp S.
Höhn M.
Popp M.
Klaus V.
Post A.
Kleinschnitz C.
Braun A.
Meuth S.
Lesch K.
Stoll G.
Kraft R.
Nieswandt B.
|
Stroke |
10.1161/STROKEAHA.119.025357 |
0 |
Ссылка
Background and Purpose- Ischemic stroke is one of the leading causes of disability and death. The principal goal of acute stroke treatment is the recanalization of the occluded cerebral arteries, which is, however, only effective in a very narrow time window. Therefore, neuroprotective treatments that can be combined with recanalization strategies are needed. Calcium overload is one of the major triggers of neuronal cell death. We have previously shown that capacitative Ca2+ entry, which is triggered by the depletion of intracellular calcium stores, contributes to ischemia-induced calcium influx in neurons, but the responsible Ca2+ channel is not known. Methods- Here, we have generated mice lacking the calcium channel subunit Orai2 and analyzed them in experimental stroke. Results- Orai2-deficient mice were protected from ischemic neuronal death both during acute ischemia under vessel occlusion and during ischemia/reperfusion upon successful recanalization. Calcium signals induced by calcium store depletion or oxygen/glucose deprivation were significantly diminished in Orai2-deficient neurons demonstrating that Orai2 is a central mediator of neuronal capacitative Ca2+ entry and is involved in calcium overload during ischemia. Conclusions- Our experimental data identify Orai2 as an attractive target for pharmaceutical intervention in acute stroke.
Читать
тезис
|
The 808 nm and 980 nm infrared laser irradiation affects spore germination and stored calcium homeostasis: A comparative study using delivery hand-pieces with standard (Gaussian) or flat-top profile
|
01.10.2019 |
Ferrando S.
Agas D.
Mirata S.
Signore A.
De Angelis N.
Ravera S.
Utyuzh A.
Parker S.
Sabbieti M.
Benedicenti S.
Amaroli A.
|
Journal of Photochemistry and Photobiology B: Biology |
10.1016/j.jphotobiol.2019.111627 |
0 |
Ссылка
© 2019 Elsevier B.V. Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellular‑calcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm2, 100 mW/cm2, 500 mW/cm2, 1000 mW/cm2, 1500 mW/cm2, 2000 mW/cm2) irradiated with a “standard” (Gaussian fluence distribution) hand-piece or with a “flat-top” (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.
Читать
тезис
|
Olesoxime in neurodegenerative diseases: Scrutinising a promising drug candidate
|
01.10.2019 |
Weber J.
Clemensson L.
Schiöth H.
Nguyen H.
|
Biochemical Pharmacology |
10.1016/j.bcp.2019.07.002 |
0 |
Ссылка
© 2019 Elsevier Inc. Over the last years, the experimental compound olesoxime, a mitochondria-targeting cholesterol derivative, has emerged as a promising drug candidate for neurodegenerative diseases. Numerous preclinical studies have successfully proved olesoxime's neuroprotective properties in cell and animal models of clinical conditions such as amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, peripheral neuropathy and spinal muscular atrophy. The beneficial effects were attributed to olesoxime's potential impact on oxidative stress, mitochondrial permeability transition or cholesterol homoeostasis. Although no significant benefits have been demonstrated in patients of amyotrophic lateral sclerosis, and only the first 12 months of a phase II/III clinical trial showed an improvement in motor symptoms of spinal muscular atrophy, this orphan drug may still offer undiscovered potential in the treatment of neurological diseases. In our earlier preclinical studies, we demonstrated that administration of olesoxime in mouse and rat models of Huntington disease improved psychiatric and molecular phenotypes. Aside from stabilising mitochondrial function, the drug reduced the overactivation of calpains, a class of calcium-dependent proteases entangled in neurodegenerative conditions. This observation may be credited to olesoxime's action on calcium dyshomeostasis, a further hallmark in neurodegeneration, and linked to its targets TSPO and VDAC, two proteins of the outer mitochondrial membrane associated with mitochondrial calcium handling. Further research into the mode of action of olesoxime under pathological conditions, including its effect on neuronal calcium homeostasis, may strengthen the untapped potential of olesoxime or other similar compounds as a therapeutic for neurodegenerative diseases.
Читать
тезис
|
Mitochondrial calcium uniporter structure and function in different types of muscle tissues in health and disease
|
01.10.2019 |
Tarasova N.
Vishnyakova P.
Logashina Y.
Elchaninov A.
|
International Journal of Molecular Sciences |
10.3390/ijms20194823 |
1 |
Ссылка
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Calcium ions (Ca2+) influx to mitochondrial matrix is crucial for the life of a cell. Mitochondrial calcium uniporter (mtCU) is a protein complex which consists of the pore-forming subunit (MCU) and several regulatory subunits. MtCU is the main contributor to inward Ca2+ currents through the inner mitochondrial membrane. Extensive investigations of mtCU involvement into normal and pathological molecular pathways started from the moment of discovery of its molecular components. A crucial role of mtCU in the control of these pathways is now recognized in both health and disease. In particular, impairments of mtCU function have been demonstrated for cardiovascular and skeletal muscle-associated pathologies. This review summarizes the current state of knowledge on mtCU structure, regulation, and function in different types of muscle tissues in health and disease.
Читать
тезис
|
Insulin Protects Cortical Neurons Against Glutamate Excitotoxicity
|
24.09.2019 |
Krasil’nikova I.
Surin A.
Sorokina E.
Fisenko A.
Boyarkin D.
Balyasin M.
Demchenko A.
Pomytkin I.
Pinelis V.
|
Frontiers in Neuroscience |
10.3389/fnins.2019.01027 |
0 |
Ссылка
© Copyright © 2019 Krasil’nikova, Surin, Sorokina, Fisenko, Boyarkin, Balyasin, Demchenko, Pomytkin and Pinelis. Glutamate excitotoxicity is implicated in the pathogenesis of numerous diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease, for which insulin resistance is a concomitant condition, and intranasal insulin treatment is believed to be a promising therapy. Excitotoxicity is initiated primarily by the sustained stimulation of ionotropic glutamate receptors and leads to a rise in intracellular Ca2+ ([Ca2+]i), followed by a cascade of intracellular events, such as delayed calcium deregulation (DCD), mitochondrial depolarization, adenosine triphosphate (ATP) depletion that collectively end in cell death. Therefore, cross-talk between insulin and glutamate signaling in excitotoxicity is of particular interest for research. In the present study, we investigated the effects of short-term insulin exposure on the dynamics of [Ca2+]i and mitochondrial potential in cultured rat cortical neurons during glutamate excitotoxicity. We found that insulin ameliorated the glutamate-evoked rise of [Ca2+]i and prevented the onset of DCD, the postulated point-of-no-return in excitotoxicity. Additionally, insulin significantly improved the glutamate-induced drop in mitochondrial potential, ATP depletion, and depletion of brain-derived neurotrophic factor (BDNF), which is a critical neuroprotector in excitotoxicity. Also, insulin improved oxygen consumption rates, maximal respiration, and spare respiratory capacity in neurons exposed to glutamate, as well as the viability of cells in the MTT assay. In conclusion, the short-term insulin exposure in our experiments was evidently a protective treatment against excitotoxicity, in a sharp contrast to chronic insulin exposure causal to neuronal insulin resistance, the adverse factor in excitotoxicity.
Читать
тезис
|
Hair Trace Element Levels in Han and Indigenous Hualien Inhabitants in Taiwan
|
15.09.2019 |
Skalny A.
Mona W.
Kao R.
Skalnaya M.
Huang P.
Wu C.
Ajsuvakova O.
Skalnaya O.
Tinkov A.
|
Biological Trace Element Research |
10.1007/s12011-018-1581-x |
0 |
Ссылка
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to assess the impact of ethnicity on hair trace element content in Han and aboriginal inhabitants of Hualien in Taiwan. Fifty Han (female/male = 35/15) and 50 aboriginal (female/male = 40/10) Hualien inhabitants aged 40–60 years were involved in the present study. Anthropometric data and dietary patterns were recorded. Hair mineral, essential, and toxic trace element levels were assessed using inductively coupled plasma mass spectrometry at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA). No group difference in gender, age, body weight, height, or physical activity was observed. Fish intake was more frequent in Han inhabitants, whereas aborigines consumed significantly more nuts. Indigenous people were characterized by higher hair Al (45%), Ca (threefold), Co (71%), Fe (twofold), I (74%), K (60%), Mg (2.5-fold), Na (62%), P (6%), Sn (78%), and V (46%) content. In turn, Han Hualien inhabitants had higher hair Be (twofold), Li, Se, Si levels as compared to indigenous counterparts. Multiple regression analysis demonstrated that ethnicity was significantly associated with hair Ca (β = 0.302), Mn (β = 0.284), P (β = 0.387), and Se (β = − 0.310) levels after adjustment for other confounders. At the same time, the overall models were significant for Ca, Mn, Se, and As. The obtained data may provide a background for monitoring and correction of trace element status in patients of different ethnic groups. However, further detailed studies are required to highlight the mechanisms underlying the observed associations.
Читать
тезис
|