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  1. Article ; Online: Isn't It Time for Establishing Mitochondrial Nomenclature Breaking Mitochondrial Paradigm?

    Zorov, Dmitry B / Andrianova, Nadezda V / Babenko, Valentina A / Zorova, Ljubava D / Zorov, Savva D / Pevzner, Irina B / Sukhikh, Gennady T / Silachev, Denis N

    Biochemistry. Biokhimiia

    2023  Volume 87, Issue 12, Page(s) 1487–1497

    Abstract: In this work, we decided to initiate a discussion concerning heterogeneity of mitochondria, suggesting that it is time to build classification of mitochondria, like the one that exists for their progenitors, α-proteobacteria, proposing possible ... ...

    Abstract In this work, we decided to initiate a discussion concerning heterogeneity of mitochondria, suggesting that it is time to build classification of mitochondria, like the one that exists for their progenitors, α-proteobacteria, proposing possible separation of mitochondrial strains and maybe species. We continue to adhere to the general line that mitochondria are friends and foes: on the one hand, they provide the cell and organism with the necessary energy and signaling molecules, and, on the other hand, participate in destruction of the cell and the organism. Current understanding that the activity of mitochondria is not only limited to energy production, but also that these alternative non-energetic functions are unique and irreplaceable in the cell, allowed us to speak about the strong subordination of the entire cellular metabolism to characteristic functional manifestations of mitochondria. Mitochondria are capable of producing not only ATP, but also iron-sulfur clusters, steroid hormones, heme, reactive oxygen and nitrogen species, participate in thermogenesis, regulate cell death, proliferation and differentiation, participate in detoxification, etc. They are a mandatory attribute of eukaryotic cells, and, so far, no eukaryotic cells performing a non-parasitic or non-symbiotic life style have been found that lack mitochondria. We believe that the structural-functional intracellular, intercellular, inter-organ, and interspecific diversity of mitochondria is large enough to provide grounds for creating a mitochondrial nomenclature. The arguments for this are given in this analytical work.
    MeSH term(s) Humans ; Mitochondria/metabolism ; Eukaryotic Cells/metabolism ; Cell Differentiation ; Oxygen/metabolism ; Reactive Oxygen Species/metabolism
    Chemical Substances Oxygen (S88TT14065) ; Reactive Oxygen Species
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297922120069
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  2. Article ; Online: Mitocentricity.

    Zorov, Dmitry B / Abramicheva, Polina A / Andrianova, Nadezda V / Babenko, Valentina A / Zorova, Ljubava D / Zorov, Savva D / Pevzner, Irina B / Popkov, Vasily A / Semenovich, Dmitry S / Yakupova, Elmira I / Silachev, Denis N / Plotnikov, Egor Y / Sukhikh, Gennady T

    Biochemistry. Biokhimiia

    2024  Volume 89, Issue 2, Page(s) 223–240

    Abstract: Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, ... ...

    Abstract Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, mitochondria are conditionally placed in a certain cellular center, which is responsible for both energy production and other non-energetic functions, without which the existence of not only the eukaryotic cell itself, but also the entire organism is impossible. Taking into account the high multifunctionality of mitochondria, such a fundamentally new scheme of cell functioning organization, including mitochondrial management of processes that determine cell survival and death, may be justified. Considering that this issue is dedicated to the memory of V. P. Skulachev, who can be called mitocentric, due to the history of his scientific activity almost entirely aimed at studying mitochondria, this work examines those aspects of mitochondrial functioning that were directly or indirectly the focus of attention of this outstanding scientist. We list all possible known mitochondrial functions, including membrane potential generation, synthesis of Fe-S clusters, steroid hormones, heme, fatty acids, and CO2. Special attention is paid to the participation of mitochondria in the formation and transport of water, as a powerful biochemical cellular and mitochondrial regulator. The history of research on reactive oxygen species that generate mitochondria is subject to significant analysis. In the section "Mitochondria in the center of death", special emphasis is placed on the analysis of what role and how mitochondria can play and determine the program of death of an organism (phenoptosis) and the contribution made to these studies by V. P. Skulachev.
    MeSH term(s) Mitochondria/metabolism ; Reactive Oxygen Species/metabolism
    Chemical Substances Reactive Oxygen Species
    Language English
    Publishing date 2024-03-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297924020044
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  3. Article: Targeting Mitochondria for Cancer Treatment.

    Zorova, Ljubava D / Abramicheva, Polina A / Andrianova, Nadezda V / Babenko, Valentina A / Zorov, Savva D / Pevzner, Irina B / Popkov, Vasily A / Semenovich, Dmitry S / Yakupova, Elmira I / Silachev, Denis N / Plotnikov, Egor Y / Sukhikh, Gennady T / Zorov, Dmitry B

    Pharmaceutics

    2024  Volume 16, Issue 4

    Abstract: There is an increasing accumulation of data on the exceptional importance of mitochondria in the occurrence and treatment of cancer, and in all lines of evidence for such participation, there are both energetic and non-bioenergetic functional features of ...

    Abstract There is an increasing accumulation of data on the exceptional importance of mitochondria in the occurrence and treatment of cancer, and in all lines of evidence for such participation, there are both energetic and non-bioenergetic functional features of mitochondria. This analytical review examines three specific features of adaptive mitochondrial changes in several malignant tumors. The first feature is characteristic of solid tumors, whose cells are forced to rebuild their energetics due to the absence of oxygen, namely, to activate the fumarate reductase pathway instead of the traditional succinate oxidase pathway that exists in aerobic conditions. For such a restructuring, the presence of a low-potential quinone is necessary, which cannot ensure the conventional conversion of succinate into fumarate but rather enables the reverse reaction, that is, the conversion of fumarate into succinate. In this scenario, complex I becomes the only generator of energy in mitochondria. The second feature is the increased proliferation in aggressive tumors of the so-called mitochondrial (peripheral) benzodiazepine receptor, also called translocator protein (TSPO) residing in the outer mitochondrial membrane, the function of which in oncogenic transformation stays mysterious. The third feature of tumor cells is the enhanced retention of certain molecules, in particular mitochondrially directed cations similar to rhodamine 123, which allows for the selective accumulation of anticancer drugs in mitochondria. These three features of mitochondria can be targets for the development of an anti-cancer strategy.
    Language English
    Publishing date 2024-03-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics16040444
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  4. Article ; Online: Targeting Inflammation and Oxidative Stress as a Therapy for Ischemic Kidney Injury.

    Andrianova, N V / Zorov, D B / Plotnikov, E Y

    Biochemistry. Biokhimiia

    2021  Volume 85, Issue 12, Page(s) 1591–1602

    Abstract: Inflammation and oxidative stress are the main pathological processes that accompany ischemic injury of kidneys and other organs. Based on this, these factors are often chosen as a target for treatment of acute kidney injury (AKI) in a variety of ... ...

    Abstract Inflammation and oxidative stress are the main pathological processes that accompany ischemic injury of kidneys and other organs. Based on this, these factors are often chosen as a target for treatment of acute kidney injury (AKI) in a variety of experimental and clinical studies. Note, that since these two components are closely interrelated during AKI development, substances that treat one of the processes often affect the other. The review considers several groups of promising nephroprotectors that have both anti-inflammatory and antioxidant effects. For example, many antioxidants, such as vitamins, polyphenolic compounds, and mitochondria-targeted antioxidants, not only reduce production of the reactive oxygen species in the cell but also modulate activity of the immune cells. On the other hand, immunosuppressors and non-steroidal anti-inflammatory drugs that primarily affect inflammation also reduce oxidative stress under some conditions. Another group of therapeutics is represented by hormones, such as estrogens and melatonin, which significantly reduce severity of the kidney damage through modulation of both these processes. We conclude that drugs with combined anti-inflammatory and antioxidant capacities are the most promising agents for the treatment of acute ischemic kidney injury.
    MeSH term(s) Acute Kidney Injury/drug therapy ; Acute Kidney Injury/metabolism ; Acute Kidney Injury/pathology ; Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Humans ; Inflammation/drug therapy ; Ischemia ; Oxidative Stress/drug effects
    Chemical Substances Anti-Inflammatory Agents ; Antioxidants
    Language English
    Publishing date 2021-03-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297920120111
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  5. Article ; Online: The Relationship of p62 Gene Expression with Integrity of Mitochondrial DNA and the Level of Lipid Peroxidation Products in Skeletal Muscles of Rats of Different Ages Exposed to Different Feeding Protocols.

    Chernyshova, E V / Gureev, A P / Sadovnikova, I S / Plotnikov, E Yu / Silachev, D N / Zorov, D B / Popov, V N

    Bulletin of experimental biology and medicine

    2023  Volume 175, Issue 2, Page(s) 245–248

    Abstract: Sequestosome-1 (SQSTM1/p62) is one of the most important multifunctional proteins, which is necessary to maintain mitochondrial stability by eliminating damaged mitochondria through mitophagy. We studied the influence of age and diet on the expression of ...

    Abstract Sequestosome-1 (SQSTM1/p62) is one of the most important multifunctional proteins, which is necessary to maintain mitochondrial stability by eliminating damaged mitochondria through mitophagy. We studied the influence of age and diet on the expression of the p62 gene in the femoral and abdominal muscles of rats, as well as the integrity of some mitochondrial components. In the femoral muscles of 24-month-old rats receiving restricted ration, the expression of the p62 gene increased. We assume that activation of mitophagy contributed to a decrease in the levels of oxidative damage to mitochondrial DNA and LPO intensity in the femoral muscles of 24-month-old rats.
    MeSH term(s) Rats ; Animals ; DNA, Mitochondrial/genetics ; DNA, Mitochondrial/metabolism ; Lipid Peroxidation ; Mitochondria/genetics ; Mitochondria/metabolism ; Muscle, Skeletal/metabolism ; Gene Expression ; Autophagy
    Chemical Substances DNA, Mitochondrial
    Language English
    Publishing date 2023-07-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390407-6
    ISSN 1573-8221 ; 0007-4888 ; 0365-9615
    ISSN (online) 1573-8221
    ISSN 0007-4888 ; 0365-9615
    DOI 10.1007/s10517-023-05843-w
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  6. Article ; Online: Anti-Inflammatory Effect of Synaptamide in Ischemic Acute Kidney Injury and the Role of G-Protein-Coupled Receptor 110.

    Brezgunova, Anna A / Andrianova, Nadezda V / Saidova, Aleena A / Potashnikova, Daria M / Abramicheva, Polina A / Manskikh, Vasily N / Mariasina, Sofia S / Pevzner, Irina B / Zorova, Ljubava D / Manzhulo, Igor V / Zorov, Dmitry B / Plotnikov, Egor Y

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to ...

    Abstract The development of drugs for the treatment of acute kidney injury (AKI) that could suppress the excessive inflammatory response in damaged kidneys is an important clinical challenge. Recently, synaptamide (N-docosahexaenoylethanolamine) has been shown to exert anti-inflammatory and neurogenic properties. The aim of this study was to investigate the anti-inflammatory effect of synaptamide in ischemic AKI. For this purpose, we analyzed the expression of inflammatory mediators and the infiltration of different leukocyte populations into the kidney after injury, evaluated the expression of the putative synaptamide receptor G-protein-coupled receptor 110 (GPR110), and isolated a population of CD11b/c
    MeSH term(s) Animals ; Rats ; Acute Kidney Injury/drug therapy ; Acute Kidney Injury/metabolism ; Anti-Inflammatory Agents/metabolism ; Ethanolamines ; Interleukins/metabolism ; Kidney/metabolism ; Receptors, G-Protein-Coupled/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Reperfusion Injury/drug therapy ; Reperfusion Injury/metabolism
    Chemical Substances Anti-Inflammatory Agents ; Ethanolamines ; Interleukins ; Receptors, G-Protein-Coupled ; synaptamide
    Language English
    Publishing date 2024-01-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031500
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  7. Article ; Online: Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury.

    Andrianova, Nadezda V / Brezgunova, Anna A / Buyan, Marina I / Makievskaya, Ciara I / Buyan, Andrey I / Cherkesova, Kseniia S / Pevzner, Irina B / Zorova, Ljubava D / Zorov, Dmitry B / Plotnikov, Egor Y / Popkov, Vasily A

    International journal of molecular sciences

    2024  Volume 25, Issue 6

    Abstract: The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of ... ...

    Abstract The positive effects of female sex hormones, particularly estradiol and progesterone, have been observed in treatment of various pathologies. Acute kidney injury (AKI) is a common condition in hospitalized patients in which the molecular mechanisms of hormone action are poorly characterized. In this study, we investigated the influence of estradiol and progesterone on renal cells during ischemic injury. We performed both in vivo experiments on female and male rats and in vitro experiments on renal tubular cells (RTCs) obtained from the kidneys of intact animals of different sexes. Since mitochondria play an important role in the pathogenesis of AKI, we analyzed the properties of individual mitochondria in renal cells, including the area, roundness, mitochondrial membrane potential, and mitochondrial permeability transition pore (mPTP) opening time. We found that pre-treatment with progesterone or estradiol attenuated the severity of ischemia/reperfusion (I/R)-induced AKI in female rats, whereas in male rats, these hormones exacerbated renal dysfunction. We demonstrated that the mPTP opening time was higher in RTCs from female rats than that in those from male rats, which may be one of the reasons for the higher tolerance of females to ischemic injury. In RTCs from the kidneys of male rats, progesterone caused mitochondrial fragmentation, which can be associated with reduced cell viability. Thus, therapy with progesterone or estradiol displays quite different effects depending on sex, and could be only effective against ischemic AKI in females.
    MeSH term(s) Humans ; Rats ; Male ; Female ; Animals ; Progesterone/adverse effects ; Estradiol/adverse effects ; Kidney/pathology ; Ischemia/complications ; Reperfusion Injury/pathology ; Acute Kidney Injury/etiology
    Chemical Substances Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2024-03-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25063155
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  8. Article: Mitochondrial ATP Synthase and Mild Uncoupling by Butyl Ester of Rhodamine 19, C4R1.

    Zorova, Ljubava D / Pevzner, Irina B / Khailova, Ljudmila S / Korshunova, Galina A / Kovaleva, Marina A / Kovalev, Leonid I / Serebryakova, Marina V / Silachev, Denis N / Sudakov, Roman V / Zorov, Savva D / Rokitskaya, Tatyana I / Popkov, Vasily A / Plotnikov, Egor Y / Antonenko, Yuri N / Zorov, Dmitry B

    Antioxidants (Basel, Switzerland)

    2023  Volume 12, Issue 3

    Abstract: The homeostasis of the transmembrane potential of hydrogen ions in mitochondria is a prerequisite for the normal mitochondrial functioning. However, in different pathological conditions it is advisable to slightly reduce the membrane potential, while ... ...

    Abstract The homeostasis of the transmembrane potential of hydrogen ions in mitochondria is a prerequisite for the normal mitochondrial functioning. However, in different pathological conditions it is advisable to slightly reduce the membrane potential, while maintaining it at levels sufficient to produce ATP that will ensure the normal functioning of the cell. A number of chemical agents have been found to provide mild uncoupling; however, natural proteins residing in mitochondrial membrane can carry this mission, such as proteins from the UCP family, an adenine nucleotide translocator and a dicarboxylate carrier. In this study, we demonstrated that the butyl ester of rhodamine 19, C4R1, binds to the components of the mitochondrial ATP synthase complex due to electrostatic interaction and has a good uncoupling effect. The more hydrophobic derivative C12R1 binds poorly to mitochondria with less uncoupling activity. Mass spectrometry confirmed that C4R1 binds to the β-subunit of mitochondrial ATP synthase and based on molecular docking, a C4R1 binding model was constructed suggesting the binding site on the interface between the α- and β-subunits, close to the anionic amino acid residues of the β-subunit. The association of the uncoupling effect with binding suggests that the ATP synthase complex can provide induced uncoupling.
    Language English
    Publishing date 2023-03-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox12030646
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  9. Article ; Online: Mitochondrial Network: Electric Cable and More.

    Abramicheva, Polina A / Andrianova, Nadezda V / Babenko, Valentina A / Zorova, Ljubava D / Zorov, Savva D / Pevzner, Irina B / Popkov, Vasily A / Semenovich, Dmitry S / Yakupova, Elmira I / Silachev, Denis N / Plotnikov, Egor Y / Sukhikh, Gennady T / Zorov, Dmitry B

    Biochemistry. Biokhimiia

    2023  Volume 88, Issue 10, Page(s) 1596–1607

    Abstract: Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the ... ...

    Abstract Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the oxidation energy of respiratory substrates is largely stored in the form of an electrical potential difference on the inner membrane of mitochondria. The theory of the functioning of extended mitochondrial structures as intracellular electrical wires suggests that mitochondria provide the fastest delivery of electrical energy through the cellular volume, followed by the use of this energy for the synthesis of ATP, thereby accelerating the process of ATP delivery compared to the rather slow diffusion of ATP in the cell. This analytical review gives the history of the cable theory, lists unsolved critical problems, describes the restructuring of the mitochondrial network and the role of oxidative stress in this process. In addition to the already proven functioning of extended mitochondrial structures as electrical cables, a number of additional functions are proposed, in particular, the hypothesis is put forth that mitochondrial networks maintain the redox potential in the cellular volume, which may vary depending on the physiological state, as a result of changes in the three-dimensional organization of the mitochondrial network (fragmentation/fission-fusion). A number of pathologies accompanied by a violation of the redox status and the participation of mitochondria in them are considered.
    MeSH term(s) Mitochondria/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Adenosine Triphosphate/metabolism
    Chemical Substances Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2023-12-16
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1109-5
    ISSN 1608-3040 ; 0006-2979 ; 0320-9717
    ISSN (online) 1608-3040
    ISSN 0006-2979 ; 0320-9717
    DOI 10.1134/S0006297923100140
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  10. Article ; Online: Is the Mitochondrial Membrane Potential (∆Ψ) Correctly Assessed? Intracellular and Intramitochondrial Modifications of the ∆Ψ Probe, Rhodamine 123.

    Zorova, Ljubava D / Demchenko, Evgeniya A / Korshunova, Galina A / Tashlitsky, Vadim N / Zorov, Savva D / Andrianova, Nadezda V / Popkov, Vasily A / Babenko, Valentina A / Pevzner, Irina B / Silachev, Denis N / Plotnikov, Egor Y / Zorov, Dmitry B

    International journal of molecular sciences

    2022  Volume 23, Issue 1

    Abstract: The mitochondrial membrane potential (∆Ψ) is the driving force providing the electrical component of the total transmembrane potential of hydrogen ions generated by proton pumps, which is utilized by the ATP synthase. The role of ∆Ψ is not limited to its ...

    Abstract The mitochondrial membrane potential (∆Ψ) is the driving force providing the electrical component of the total transmembrane potential of hydrogen ions generated by proton pumps, which is utilized by the ATP synthase. The role of ∆Ψ is not limited to its role in bioenergetics since it takes part in other important intracellular processes, which leads to the mandatory requirement of the homeostasis of ∆Ψ. Conventionally, ∆Ψ in living cells is estimated by the fluorescence of probes such as rhodamine 123, tetramethylrodamine, etc. However, when assessing the fluorescence, the possibility of the intracellular/intramitochondrial modification of the rhodamine molecule is not taken into account. Such changes were revealed in this work, in which a comparison of normal (astrocytic) and tumor (glioma) cells was conducted. Fluorescent microscopy, flow cytometry, and mass spectrometry revealed significant modifications of rhodamine molecules developing over time, which were prevented by amiodarone apparently due to blocking the release of xenobiotics from the cell and their transformation with the participation of cytochrome P450. Obviously, an important role in these processes is played by the increased retention of rhodamines in tumor cells. Our data require careful evaluation of mitochondrial ∆Ψ potential based on the assessment of the fluorescence of the mitochondrial probe.
    MeSH term(s) Animals ; Astrocytes/metabolism ; Cell Extracts ; Cell Line, Tumor ; Fluorescence ; Glioma/metabolism ; Membrane Potential, Mitochondrial ; Mitochondria/metabolism ; Molecular Probes/metabolism ; Rats ; Rhodamine 123/metabolism ; Time Factors
    Chemical Substances Cell Extracts ; Molecular Probes ; Rhodamine 123 (1N3CZ14C5O)
    Language English
    Publishing date 2022-01-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23010482
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