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Article ; Online: CD160 receptor in CLL: Current state and future avenues.

Oumeslakht, Loubna / Aziz, Abdel-Ilah / Bensussan, Armand / Ben Mkaddem, Sanae

2022 Volume 13, Page(s) 1028013

Abstract: CD160 is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein expressed on cytotoxic natural killer (NK) cells and T-cell subsets. It plays a crucial role in the activation of NK-cell cytotoxicity and cytokine production. It also ... ...

Abstract	CD160 is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein expressed on cytotoxic natural killer (NK) cells and T-cell subsets. It plays a crucial role in the activation of NK-cell cytotoxicity and cytokine production. It also modulates the immune system and is involved in some pathologies, such as cancer. CD160 is abnormally expressed in B-cell chronic lymphocytic leukemia (CLL) but not expressed in normal B lymphocytes. Its expression in CLL enhances tumor cell proliferation and resistance to apoptosis. CD160 is also a potential prognostic marker for the detection of minimal residual disease (MRD) in CLL, which is important for the clinical management of CLL, the prevention of disease relapse, and the achievement of complete remission. In this review, we present an overview of CD160 and its involvement in the pathophysiology of CLL. We also discuss its use as a prognostic marker for the assessment of MRD in CLL.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Receptors, Immunologic/metabolism ; Antigens, CD/metabolism ; GPI-Linked Proteins/metabolism ; Killer Cells, Natural/metabolism ; Glycosylphosphatidylinositols ; Neoplasm, Residual
Chemical Substances	Receptors, Immunologic ; Antigens, CD ; GPI-Linked Proteins ; Glycosylphosphatidylinositols ; CD160 protein, human
Language	English
Publishing date	2022-11-07
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1028013
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Article ; Online: Worldwide genetic variations in high-risk human papillomaviruses capsid L1 gene and their impact on vaccine efficiency.

Oumeslakht, Loubna / Ababou, Mouna / Badaoui, Bouabid / Qmichou, Zineb

Gene

2021 Volume 782, Page(s) 145533

Abstract: Background: Human papillomavirus is the most common sexually transmitted infection. It is associated with different cancers, mainly cervical cancer, which remains the fourth most frequent cancer among women worldwide; it is also related to anogenital ( ... ...

Abstract	Background: Human papillomavirus is the most common sexually transmitted infection. It is associated with different cancers, mainly cervical cancer, which remains the fourth most frequent cancer among women worldwide; it is also related to anogenital (anus, vulvar, vagina, and penis) and oropharyngeal cancers. Vaccination against HPV infection is the major way of prevention, and it has demonstrated impressive efficacy in reducing cervical cancer incidence. Nowadays, all the licensed HPV recombinant vaccines were designed based on HPV major capsid L1 protein. However, some variations in the HPV L1 gene sequence may induce structural changes within the L1 protein, which may alter the affinity and interaction of monoclonal antibodies (MAbs) with L1 protein epitopes, and influence host immune response and recognition. Hence, the importance of accuracy in delineating epitopes relevant to vaccine design and defining genetic variations within antigenic regions in the L1 gene to predict its impact on prophylactic vaccine efficiency. The present review reports the sequence variations in HR-HPV L1 gene isolates from different countries around the world, which may help to understand the effect of HPV L1 gene variations on vaccine efficiency. Methods: Research studies were retrieved from PubMed, Google Scholar, Science direct, and the National Center for Biotechnology Information (NCBI) database. A total of 31 articles describing genetic variations within the major capsid L1 gene and conducted in Africa, Europe, America and Asia were found. Only 26 studies conducted on HPV16, 18, 31, 33, 58, 45 and 52 which are the targets of HPV prophylactic vaccines, and which reported genetic variations within the L1 gene, were selected and evaluated in this review. Findings: We found a total of 87, 49, 11, 7, 22, 3, and 17 non-synonymous single nucleotide polymorphisms (SNPs) within HPV16, HPV18, HPV31, HPV58, HPV45, and HPV52 L1 gene, respectively. Four mutations were frequently observed in HPV16 L1 sequences: T353P in the HI loop, H228D in the EF loop, T266A in the FG loop, and T292A in the FG loop. Two mutations in HPV58 L1 sequences: T375N in the HI loop and L150F in the DE loop. Three mutations in HPV33 L1 sequences: T56N in the BC loop, G133S in the DE loop, T266K in the FG loop. Other mutations were found in HPV18, HPV45, and HPV52 L1 sequences. Some were found in different countries, and others were specific to a given population. Furthermore, some variations were located on peptide binding epitopes and lead to a modification of epitopes, which may influence MAbs interactions. Others need further investigations due to the lack of studies. Conclusion: This study investigated the major capsid L1 genetic diversity of HPV16, 18, 31, 33, 58, 45, and 52 circulating in different populations around the world. Further investigations should be conducted to confirm their effect on immunogenicity and prophylactic vaccine efficiency.
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; Antibody Affinity ; Capsid Proteins/genetics ; Capsid Proteins/immunology ; Genetic Variation ; Global Health ; Humans ; Immunogenicity, Vaccine/genetics ; Oncogene Proteins, Viral/genetics ; Oncogene Proteins, Viral/immunology ; Papillomaviridae/genetics ; Papillomaviridae/physiology ; Papillomavirus Vaccines/genetics ; Papillomavirus Vaccines/immunology
Chemical Substances	Antibodies, Viral ; Capsid Proteins ; HPV L1 protein, Human papillomavirus ; Oncogene Proteins, Viral ; Papillomavirus Vaccines
Language	English
Publishing date	2021-02-23
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145533
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Article: Worldwide genetic variations in high-risk human papillomaviruses capsid L1 gene and their impact on vaccine efficiency

Oumeslakht, Loubna / Ababou, Mouna / Badaoui, Bouabid / Qmichou, Zineb

Gene. 2021 May 25, v. 782

2021

Abstract: Human papillomavirus is the most common sexually transmitted infection. It is associated with different cancers, mainly cervical cancer, which remains the fourth most frequent cancer among women worldwide; it is also related to anogenital (anus, vulvar, ... ...

Abstract	Human papillomavirus is the most common sexually transmitted infection. It is associated with different cancers, mainly cervical cancer, which remains the fourth most frequent cancer among women worldwide; it is also related to anogenital (anus, vulvar, vagina, and penis) and oropharyngeal cancers. Vaccination against HPV infection is the major way of prevention, and it has demonstrated impressive efficacy in reducing cervical cancer incidence. Nowadays, all the licensed HPV recombinant vaccines were designed based on HPV major capsid L1 protein. However, some variations in the HPV L1 gene sequence may induce structural changes within the L1 protein, which may alter the affinity and interaction of monoclonal antibodies (MAbs) with L1 protein epitopes, and influence host immune response and recognition. Hence, the importance of accuracy in delineating epitopes relevant to vaccine design and defining genetic variations within antigenic regions in the L1 gene to predict its impact on prophylactic vaccine efficiency. The present review reports the sequence variations in HR-HPV L1 gene isolates from different countries around the world, which may help to understand the effect of HPV L1 gene variations on vaccine efficiency.Research studies were retrieved from PubMed, Google Scholar, Science direct, and the National Center for Biotechnology Information (NCBI) database. A total of 31 articles describing genetic variations within the major capsid L1 gene and conducted in Africa, Europe, America and Asia were found. Only 26 studies conducted on HPV16, 18, 31, 33, 58, 45 and 52 which are the targets of HPV prophylactic vaccines, and which reported genetic variations within the L1 gene, were selected and evaluated in this review.We found a total of 87, 49, 11, 7, 22, 3, and 17 non-synonymous single nucleotide polymorphisms (SNPs) within HPV16, HPV18, HPV31, HPV58, HPV45, and HPV52 L1 gene, respectively. Four mutations were frequently observed in HPV16 L1 sequences: T353P in the HI loop, H228D in the EF loop, T266A in the FG loop, and T292A in the FG loop. Two mutations in HPV58 L1 sequences: T375N in the HI loop and L150F in the DE loop. Three mutations in HPV33 L1 sequences: T56N in the BC loop, G133S in the DE loop, T266K in the FG loop. Other mutations were found in HPV18, HPV45, and HPV52 L1 sequences. Some were found in different countries, and others were specific to a given population. Furthermore, some variations were located on peptide binding epitopes and lead to a modification of epitopes, which may influence MAbs interactions. Others need further investigations due to the lack of studies.This study investigated the major capsid L1 genetic diversity of HPV16, 18, 31, 33, 58, 45, and 52 circulating in different populations around the world. Further investigations should be conducted to confirm their effect on immunogenicity and prophylactic vaccine efficiency.
Keywords	National Center for Biotechnology Information ; Papillomaviridae ; anus ; capsid ; databases ; epitopes ; genes ; genetic variation ; humans ; immune response ; immunogenicity ; nucleotide sequences ; penis ; peptides ; sexually transmitted diseases ; uterine cervical neoplasms ; vaccination ; vaccine development ; vagina ; Africa ; Asia ; Europe
Language	English
Dates of publication	2021-0525
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2021.145533
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Cannabinoids as Immune System Modulators: Cannabidiol Potential Therapeutic Approaches and Limitations.

Aziz, Abdel-Ilah / Nguyen, Long Chi / Oumeslakht, Loubna / Bensussan, Armand / Ben Mkaddem, Sanae

Cannabis and cannabinoid research

2022 Volume 8, Issue 2, Page(s) 254–269

Abstract: Introduction: ...

Abstract	Introduction:
MeSH term(s)	United States ; Child ; Humans ; Cannabinoids/pharmacology ; Cannabinoids/therapeutic use ; Cannabidiol/pharmacology ; Cannabidiol/therapeutic use ; Endocannabinoids/metabolism ; COVID-19 ; Cannabis ; Hallucinogens ; Cannabinoid Receptor Agonists ; Immunologic Factors ; Inflammatory Bowel Diseases/drug therapy
Chemical Substances	Cannabinoids ; Cannabidiol (19GBJ60SN5) ; Endocannabinoids ; Hallucinogens ; Cannabinoid Receptor Agonists ; Immunologic Factors
Language	English
Publishing date	2022-11-22
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2022.0133
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Article ; Online: Fc receptors act as innate immune receptors during infection?

Laassili, Chaimaa / Ben El Hend, Fatiha / Benzidane, Riad / Oumeslakht, Loubna / Aziz, Abdel-Ilah / El Fatimy, Rachid / Bensussan, Armand / Ben Mkaddem, Sanae

Frontiers in immunology

2023 Volume 14, Page(s) 1188497

Abstract: Innate immunity constitutes the first nonspecific immunological line of defense against infection. In this response, a variety of mechanisms are activated: the complement system, phagocytosis, and the inflammatory response. Then, adaptive immunity is ... ...

Abstract	Innate immunity constitutes the first nonspecific immunological line of defense against infection. In this response, a variety of mechanisms are activated: the complement system, phagocytosis, and the inflammatory response. Then, adaptive immunity is activated. Major opsonization mediators during infections are immunoglobulins (Igs), the function of which is mediated through Fc receptors (FcRs). However, in addition to their role in adaptive immunity, FcRs have been shown to play a role in innate immunity by interacting directly with bacteria in the absence of their natural ligands (Igs). Additionally, it has been hypothesized that during the early phase of bacterial infection, FcRs play a protective role via innate immune functions mediated through direct recognition of bacteria, and as the infection progresses to later phases, FcRs exhibit their established function as receptors in adaptive immunity. This review provides detailed insight into the potential role of FcRs as innate immune mediators of the host defense against bacterial infection independent of opsonins.
MeSH term(s)	Receptors, Fc ; Immunity, Innate ; Phagocytosis ; Immunoglobulins ; Complement System Proteins
Chemical Substances	Receptors, Fc ; Immunoglobulins ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2023-07-26
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1188497
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Article ; Online: Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice.

Kabach, Imad / Bouchmaa, Najat / Zouaoui, Zakia / Ennoury, Abdelhamid / El Asri, Sara / Laabar, Abdelmounaim / Oumeslakht, Loubna / Cacciola, Francesco / El Majdoub, Yassine Oulad / Mondello, Luigi / Zyad, Abdelmajid / Nhiri, Naima / Nhiri, Mohamed / Ben Mrid, Reda

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 160, Page(s) 114393

Abstract: Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of ... ...

Abstract	Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS
MeSH term(s)	Mice ; Animals ; Antioxidants/therapeutic use ; alpha-Glucosidases ; Alloxan ; alpha-Amylases ; Diabetes Mellitus, Experimental/drug therapy ; Plant Extracts/pharmacology ; Plant Extracts/therapeutic use ; Plant Extracts/chemistry ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Hyperglycemia/drug therapy ; Phytochemicals/pharmacology ; Phytochemicals/therapeutic use ; Glycation End Products, Advanced
Chemical Substances	Antioxidants ; alpha-Glucosidases (EC 3.2.1.20) ; Alloxan (6SW5YHA5NG) ; alpha-Amylases (EC 3.2.1.1) ; Plant Extracts ; Hypoglycemic Agents ; Phytochemicals ; Glycation End Products, Advanced
Language	English
Publishing date	2023-02-10
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.114393
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Article ; Online: The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions.

Bouyahya, Abdelhakim / Mechchate, Hamza / Oumeslakht, Loubna / Zeouk, Ikrame / Aboulaghras, Sara / Balahbib, Abdelaali / Zengin, Gokhan / Kamal, Mohammad Amjad / Gallo, Monica / Montesano, Domenico / El Omari, Nasreddine

Biomolecules

2022 Volume 12, Issue 3

Abstract: Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a ... ...

Abstract	Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.
MeSH term(s)	DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Flavonoids ; Histones/metabolism ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Plants, Medicinal/chemistry
Chemical Substances	Flavonoids ; Histones
Language	English
Publishing date	2022-02-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12030367
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Article: Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells.

Bouyahya, Abdelhakim / El Menyiy, Naoual / Oumeslakht, Loubna / El Allam, Aicha / Balahbib, Abdelaali / Rauf, Abdur / Muhammad, Naveed / Kuznetsova, Elena / Derkho, Marina / Thiruvengadam, Muthu / Shariati, Mohammad Ali / El Omari, Nasreddine

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 10

Abstract: ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. ...

Abstract	ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. In general, there is an equilibrium between the synthesis of ROS and their reduction by the natural antioxidant defense system, called the redox system. Therefore, when this balance is upset, the excess ROS production can affect different macromolecules, such as proteins, lipids, nucleic acids, and sugars, which can lead to an electronic imbalance than oxidation of these macromolecules. Recently, it has also been shown that ROS produced at the cellular level can affect different signaling pathways that participate in the stimulation of transcription factors linked to cell proliferation and, consequently, to the carcinogenesis process. Indeed, ROS can activate the pathway of tyrosine kinase, MAP kinase, IKK, NF-KB, phosphoinositol 3 phosphate, and hypoxia-inducible factor (HIF). The activation of these signaling pathways directly contributes to the accelerated proliferation process and, as a result, the appearance of cancer. In addition, the use of antioxidants, especially natural ones, is now a major issue in the approach to cancer prevention. Some natural molecules, especially phytochemicals isolated from medicinal plants, have now shown interesting preclinical and clinical results.
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10101553
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Article: Preclinical and Clinical Antioxidant Effects of Natural Compounds against Oxidative Stress-Induced Epigenetic Instability in Tumor Cells

Antioxidants. 2021 Sept. 29, v. 10, no. 10

2021

Abstract	ROS (reactive oxygen species) are produced via the noncomplete reduction in molecular oxygen in the mitochondria of higher organisms. The produced ROS are placed in various cell compartments, such as the mitochondria, cytoplasm, and endoplasmic reticulum. In general, there is an equilibrium between the synthesis of ROS and their reduction by the natural antioxidant defense system, called the redox system. Therefore, when this balance is upset, the excess ROS production can affect different macromolecules, such as proteins, lipids, nucleic acids, and sugars, which can lead to an electronic imbalance than oxidation of these macromolecules. Recently, it has also been shown that ROS produced at the cellular level can affect different signaling pathways that participate in the stimulation of transcription factors linked to cell proliferation and, consequently, to the carcinogenesis process. Indeed, ROS can activate the pathway of tyrosine kinase, MAP kinase, IKK, NF-KB, phosphoinositol 3 phosphate, and hypoxia-inducible factor (HIF). The activation of these signaling pathways directly contributes to the accelerated proliferation process and, as a result, the appearance of cancer. In addition, the use of antioxidants, especially natural ones, is now a major issue in the approach to cancer prevention. Some natural molecules, especially phytochemicals isolated from medicinal plants, have now shown interesting preclinical and clinical results.
Keywords	antioxidant activity ; carcinogenesis ; cell proliferation ; endoplasmic reticulum ; epigenetics ; mitochondria ; mitogen-activated protein kinase ; neoplasms ; oxidation ; oxygen ; phosphates ; phytochemicals ; reactive oxygen species ; transcription factor NF-kappa B ; tyrosine
Language	English
Dates of publication	2021-0929
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10101553
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