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Article ; Online: Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.

Zheng, Yadong / Bonfili, Laura / Wei, Tao / Eleuteri, Anna Maria

2023 Volume 15, Issue 21

Abstract: The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). ... ...

Abstract	The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.
MeSH term(s)	Humans ; Brain-Gut Axis ; Neurodegenerative Diseases/therapy ; Gastrointestinal Microbiome ; Alzheimer Disease/therapy ; Parkinson Disease/therapy ; Brain ; Dysbiosis/therapy
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15214631
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Article ; Online: Electrospinning and Electrospraying: Emerging Techniques for Probiotic Stabilization and Application.

Feng, Kun / Huangfu, Lulu / Liu, Chuanduo / Bonfili, Laura / Xiang, Qisen / Wu, Hong / Bai, Yanhong

Polymers

2023 Volume 15, Issue 10

Abstract: Probiotics are beneficial for human health. However, they are vulnerable to adverse effects during processing, storage, and passage through the gastrointestinal tract, thus reducing their viability. The exploration of strategies for probiotic ... ...

Abstract	Probiotics are beneficial for human health. However, they are vulnerable to adverse effects during processing, storage, and passage through the gastrointestinal tract, thus reducing their viability. The exploration of strategies for probiotic stabilization is essential for application and function. Electrospinning and electrospraying, two electrohydrodynamic techniques with simple, mild, and versatile characteristics, have recently attracted increased interest for encapsulating and immobilizing probiotics to improve their survivability under harsh conditions and promoting high-viability delivery in the gastrointestinal tract. This review begins with a more detailed classification of electrospinning and electrospraying, especially dry electrospraying and wet electrospraying. The feasibility of electrospinning and electrospraying in the construction of probiotic carriers, as well as the efficacy of various formulations on the stabilization and colonic delivery of probiotics, are then discussed. Meanwhile, the current application of electrospun and electrosprayed probiotic formulations is introduced. Finally, the existing limitations and future opportunities for electrohydrodynamic techniques in probiotic stabilization are proposed and analyzed. This work comprehensively explains how electrospinning and electrospraying are used to stabilize probiotics, which may aid in their development in probiotic therapy and nutrition.
Language	English
Publishing date	2023-05-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527146-5
ISSN	2073-4360 ; 2073-4360
ISSN (online)	2073-4360
ISSN	2073-4360
DOI	10.3390/polym15102402
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Article ; Online: Probiotics Supplementation Attenuates Inflammation and Oxidative Stress Induced by Chronic Sleep Restriction.

Zheng, Yadong / Zhang, Luyan / Bonfili, Laura / de Vivo, Luisa / Eleuteri, Anna Maria / Bellesi, Michele

Nutrients

2023 Volume 15, Issue 6

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Mice ; Animals ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Oxidative Stress ; Inflammation/etiology ; Sleep Deprivation/complications ; Probiotics ; Anti-Inflammatory Agents/pharmacology ; Sleep Initiation and Maintenance Disorders/complications ; Hormones/pharmacology
Chemical Substances	Antioxidants ; Anti-Inflammatory Agents ; Hormones
Language	English
Publishing date	2023-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15061518
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Article: Ginsenosides Rg1 and Rg2 Activate Autophagy and Attenuate Oxidative Stress in Neuroblastoma Cells Overexpressing Aβ(1-42).

Liu, Ziqi / Cecarini, Valentina / Cuccioloni, Massimiliano / Bonfili, Laura / Gong, Chunmei / Angeletti, Mauro / Eleuteri, Anna Maria

Antioxidants (Basel, Switzerland)

2024 Volume 13, Issue 3

Abstract: Alzheimer's disease is a neurodegeneration with protein deposits, altered proteolysis, and inflammatory and oxidative processes as major hallmarks. Despite the continuous search for potential therapeutic treatments, no cure is available to date. The use ... ...

Abstract	Alzheimer's disease is a neurodegeneration with protein deposits, altered proteolysis, and inflammatory and oxidative processes as major hallmarks. Despite the continuous search for potential therapeutic treatments, no cure is available to date. The use of natural molecules as adjuvants in the treatment of Alzheimer's disease is a very promising strategy. In this regard, ginsenosides from ginseng root show a variety of biological effects. Here, we dissected the role of ginsenosides Rg1 and Rg2 in modulating autophagy and oxidative stress in neuroblastoma cells overexpressing Aβ(1-42). Key hallmarks of these cellular processes were detected through immunomethods and fluorometric assays. Our findings indicate that ginsenosides are able to upregulate autophagy in neuronal cells as demonstrated by increased levels of LC3II and Beclin-1 proteins and decreased amounts of p62. Simultaneously, an activation of lysosomal hydrolases was observed. Furthermore, autophagy activation promoted the clearance of Aβ(1-42). Rg1 and Rg2 also reduced oxidative stress sources and macromolecule oxidation, promoting NRF2 nuclear translocation and the expression of antioxidant enzymes. Our data further clarify the mechanisms of action of Rg1 and Rg2, indicating new insights into their role in the management of disorders like Alzheimer's disease.
Language	English
Publishing date	2024-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox13030310
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Article ; Online: Gut Microbiome and Mycobiome Alterations in an In Vivo Model of Alzheimer's Disease.

D'Argenio, Valeria / Veneruso, Iolanda / Gong, Chunmei / Cecarini, Valentina / Bonfili, Laura / Eleuteri, Anna Maria

Genes

2022 Volume 13, Issue 9

Abstract: Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have ...

Abstract	Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer's disease (AD), suggesting possible pathogenetic mechanisms contributing to the development of specific AD hallmarks and exacerbating metabolic alterations and neuroinflammation. The identification of these mechanisms is crucial to develop novel, targeted therapies and identify potential biomarkers for diagnostic purposes. Thus, the possibility to have AD in vivo models to study this microbial ecosystem represents a great opportunity for translational applications. Here, we characterized both gut microbiome and mycobiome of 3xTg-AD mice, one of the most widely used AD models, to identify specific microbial alterations with respect to the wild-type counterpart. Interestingly, we found a significant reduction of the
MeSH term(s)	Alzheimer Disease/metabolism ; Animals ; Biomarkers ; Dysbiosis ; Ecosystem ; Gastrointestinal Microbiome ; Mice ; Mycobiome
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-08-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13091564
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Article: Gut Microbiome and Mycobiome Alterations in an In Vivo Model of Alzheimer’s Disease

D’Argenio, Valeria / Veneruso, Iolanda / Gong, Chunmei / Cecarini, Valentina / Bonfili, Laura / Eleuteri, Anna Maria

Genes. 2022 Aug. 31, v. 13, no. 9

2022

Abstract	Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer’s disease (AD), suggesting possible pathogenetic mechanisms contributing to the development of specific AD hallmarks and exacerbating metabolic alterations and neuroinflammation. The identification of these mechanisms is crucial to develop novel, targeted therapies and identify potential biomarkers for diagnostic purposes. Thus, the possibility to have AD in vivo models to study this microbial ecosystem represents a great opportunity for translational applications. Here, we characterized both gut microbiome and mycobiome of 3xTg-AD mice, one of the most widely used AD models, to identify specific microbial alterations with respect to the wild-type counterpart. Interestingly, we found a significant reduction of the Coprococcus and an increased abundance of Escherichia_Shigella and Barnesiella genera in the AD mice compatible with a pro-inflammatory status and the development of AD-related pathogenetic features. Moreover, the fungal Dipodascaceae family was significantly increased, thus suggesting a possible contribution to the metabolic alterations found in AD. Our data point out the strict connection between bacterial dysbiosis and AD and, even if further studies are required to clarify the underlining mechanisms, it clearly indicates the need for extensive metagenomic studies over the bacterial counterpart.
Keywords	Coprococcus ; Dipodascaceae ; biomarkers ; dysbiosis ; fungi ; intestinal microorganisms ; metagenomics ; microbial ecology ; models
Language	English
Dates of publication	2022-0831
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13091564
Database	NAL-Catalogue (AGRICOLA)

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Article: Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism

Bonfili, Laura / Cuccioloni, Massimiliano / Gong, Chunmei / Cecarini, Valentina / Spina, Michele / Zheng, Yadong / Angeletti, Mauro / Eleuteri, Anna Maria

Clinical nutrition. 2022 Mar., v. 41, no. 3

2022

Abstract: Alzheimer's disease (AD) and age-related dementias represent a major and increasing global health challenge. Unhealthy diet and lifestyle can unbalance the intestinal microbiota composition and, consequently energy metabolism, contributing to AD ... ...

Abstract	Alzheimer's disease (AD) and age-related dementias represent a major and increasing global health challenge. Unhealthy diet and lifestyle can unbalance the intestinal microbiota composition and, consequently energy metabolism, contributing to AD pathogenesis. Impairment of cerebral cholesterol metabolism occurs in both aging and AD, and lipid-lowering agents have been associated to a lower risk of neurodegenerative diseases, but the link between blood lipid profile and AD remains a matter of debate. Recently, probiotics have emerged as a promising and safe strategy to manipulate gut microbiota composition and increase the host health status through a multi-level mechanism that is currently under investigation. Specifically, oral supplementation with a multi-strain probiotic formulation (SLAB51) reduced amyloid beta aggregates and brain damages in a triple transgenic mouse model of AD (3xTg-AD). Treated mice showed improved cognitive functions in response to an enrichment of gut anti-inflammatory metabolites, increased plasma concentrations of neuroprotective gut hormones, and ameliorated glucose uptake and metabolism. This work focuses on the evaluation of the effects of SLAB51 chronic administration on lipid metabolism in 3xTg-AD mice and the respective wild-type counterpart. On this purpose, 8 weeks old mice were orally administered with SLAB51 for 4 and 12 months to analyze the plasma lipid profile (using lipidomic analyses and enzymatic colorimetric assays), along with the cerebral and hepatic expression levels of key regulators of cholesterol metabolism (through Western blotting and ELISA). Upon probiotics administration, cholesterol biosynthesis was inhibited in AD mice with a process involving sterol regulatory element binding protein 1c and liver X receptors mediated pathways. Decreased plasma and brain concentration of 27-hydroxycholesterol and increased brain expression of cholesterol 24S-hydroxylase indicated that alternative pathways of bile acid synthesis are influenced. The plasmatic increase of arachidonic acid in treated AD mice reflects dynamic interactions among several actors of a complex inflammatory response, in which polyunsaturated fatty acids can compete each other and simultaneously co-operate in the resolution of inflammation. These evidence, together with the hypocholesterolemic effects, the ameliorated fatty acids profile and the decreased omega 6/omega 3 ratio successfully demonstrated that microbiota modulation through probiotics can positively change lipid composition in AD mice, with arachidonic acid representing one important hub metabolite in the interactions among probiotic-induced lipid profile changes, insulin sensitivity, and inflammation.
Keywords	Alzheimer disease ; amyloid ; arachidonic acid ; bile acids ; biosynthesis ; blood lipids ; brain ; cholesterol ; cholesterol metabolism ; clinical nutrition ; cognition ; colorimetry ; diet ; energy metabolism ; glucose ; health status ; inflammation ; insulin resistance ; intestinal microorganisms ; lifestyle ; lipidomics ; liver ; metabolites ; mice ; pathogenesis ; probiotics ; risk
Language	English
Dates of publication	2022-03
Size	p. 698-708.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2022.01.025
Database	NAL-Catalogue (AGRICOLA)

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Article: Assessment of serum amyloid A concentrations and biochemical profiles in lactating jennies and newborn Ragusano donkey foals around parturition and one month after foaling in Sicily

Bazzano, Marilena / Bonfili, Laura / Eleuteri, Anna Maria / Serri, Evelina / Scollo, Carmela / Yaosen, Yang / Tesei, Beniamino / Laus, Fulvio

Reproduction in domestic animals. 2022 Mar., v. 57, no. 3

2022

Abstract: A proper knowledge of biochemical parameters and inflammatory markers like serum amyloid A (SAA) is crucial in the monitoring of the first post‐partum period in equids. Since no information is available on SAA for donkeys at this stage, 50 animals ... ...

Abstract	A proper knowledge of biochemical parameters and inflammatory markers like serum amyloid A (SAA) is crucial in the monitoring of the first post‐partum period in equids. Since no information is available on SAA for donkeys at this stage, 50 animals including jennies (n.10) and newborn foals (n.10) within 48 hr from foaling, and jennies (n.10) and foals (n.20) after 30 days from parturition were enrolled in the study to assess routine biochemical profile including SAA. Jennies showed higher alkaline phosphatase and lower bilirubins and cholesterol at 30 days of lactation compared to post‐partum. Neonatal donkey foals showed significant higher concentrations of sodium, alkaline phosphatase, lactic dehydrogenase, blood urea nitrogen, creatinine and albumin within 48 hr of age, whilst higher values of phosphate and triglycerides were observed in older foals of 30 days of age. Significant higher SAA concentrations were recorded during the peripartum period in both jennies (25.95 ± 14.98 μg/ml) and newborn donkey foals (37.44 ± 19.75 μg/ml) compared to SAA values recorded in lactating jennies (2.38 ± 1.78 μg/ml) and in donkey foals (16.04 ± 18.14 μg/ml) at 30 days after parturition. The assessment of SAA in jennies and donkey foals around parturition and one month after foaling represents a valuable tool for the monitoring of health status during this stage when animals have to face with new challenges like the peak of lactation and extrauterine life adaptation respectively.
Keywords	Equidae ; albumins ; alkaline phosphatase ; amyloid ; asses ; blood serum ; cholesterol ; creatinine ; health status ; lactation ; neonates ; oxidoreductases ; phosphates ; postpartum period ; sodium ; urea nitrogen ; Sicily
Language	English
Dates of publication	2022-03
Size	p. 262-268.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	1015187-4
ISSN	1439-0531 ; 0936-6768
ISSN (online)	1439-0531
ISSN	0936-6768
DOI	10.1111/rda.14048
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer's Disease.

Bonfili, Laura / Gong, Chunmei / Lombardi, Francesca / Cifone, Maria Grazia / Eleuteri, Anna Maria

International journal of molecular sciences

2021 Volume 23, Issue 1

Abstract: Dysbiosis contributes to Alzheimer's disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and ... ...

Abstract	Dysbiosis contributes to Alzheimer's disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.
MeSH term(s)	Administration, Oral ; Alzheimer Disease/blood ; Alzheimer Disease/microbiology ; Alzheimer Disease/therapy ; Animals ; Gastrointestinal Microbiome/drug effects ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Mice, Transgenic ; Mouth/microbiology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/metabolism ; Nitrites/blood ; Probiotics/administration & dosage ; Probiotics/pharmacology ; Prolyl Hydroxylases/metabolism
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit ; Nitrites ; Nitric Oxide (31C4KY9ESH) ; Prolyl Hydroxylases (EC 1.14.11.-) ; Nitric Oxide Synthase Type II (EC 1.14.13.39)
Language	English
Publishing date	2021-12-29
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/ijms23010357
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Article ; Online: Microglial polarization differentially affects neuronal vulnerability to the β-amyloid protein: Modulation by melatonin.

Merlo, Sara / Caruso, Grazia Ilaria / Bonfili, Laura / Spampinato, Simona Federica / Costantino, Giuseppe / Eleuteri, Anna Maria / Sortino, Maria Angela

Biochemical pharmacology

2022 Volume 202, Page(s) 115151

Abstract: Microglial cells play a central but yet debated role in neuroinflammatory events occurring in Alzheimer's disease (AD). We here explored how microglial features are modulated by melatonin following β-amyloid (Aβ42)-induced activation and examined the ... ...

Abstract	Microglial cells play a central but yet debated role in neuroinflammatory events occurring in Alzheimer's disease (AD). We here explored how microglial features are modulated by melatonin following β-amyloid (Aβ42)-induced activation and examined the cross-talk with Aβ-challenged neuronal cells. Human microglial HMC3 cells were exposed to Aβ42 (200 nM) in the presence of melatonin (MEL; 1 μM) added since the beginning (MELco) or after a 72 h-exposure to Aβ42 (MELpost). In both conditions, MEL favored an anti-inflammatory activation and rescued SIRT1 and BDNF expression/release. Caspase-1 up-regulation and phospho-ERK induction following a prolonged exposure to Aβ42 were prevented by MEL. In addition, MEL partially restored proteasome functionality that was altered by long-term Aβ42 treatment, re-establishing both 20S and 26S chymotrypsin-like activity. Differentiated neuronal-like SH-SY5Y cells were exposed to Aβ42 (200 nM for 24 h) in basal medium or in the presence of conditioned medium (CM) collected from microglia exposed for different times to Aβ42 alone or in combination with MELco or MELpost. Aβ42 significantly reduced pre-synaptic proteins synaptophysin and VAMP2 and mean neuritic length. These effects were prevented by CM from anti-inflammatory microglia (Aβ42 for 6 h), or from MELco and MELpost microglia, but the reduction of neuritic length was not rescued when the SIRT1 inhibitor EX527 was added. In conclusion, our data add to the concept that melatonin shows a promising anti-inflammatory action on microglia that is retained even after pro-inflammatory activation, involving modulation of proteasome function and translating into neuroprotective microglial effects.
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Anti-Inflammatory Agents/pharmacology ; Humans ; Melatonin/metabolism ; Microglia ; Neuroblastoma/metabolism ; Neuroprotective Agents/pharmacology ; Peptide Fragments/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Sirtuin 1/metabolism
Chemical Substances	Amyloid beta-Peptides ; Anti-Inflammatory Agents ; Neuroprotective Agents ; Peptide Fragments ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Sirtuin 1 (EC 3.5.1.-) ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2022-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2022.115151
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