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  1. Article ; Online: Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of alzheimer's disease.

    Govindarajan, Karthivashan / Kar, Satyabrata

    Journal of nanobiotechnology

    2023  Volume 21, Issue 1, Page(s) 216

    Abstract: Evidence suggests that increased level/aggregation of β-amyloid (Aβ) peptide, together with enhanced phosphorylation/aggregation of tau protein, play a critical role in the development of Alzheimer's disease (AD), the leading cause of dementia in the ... ...

    Abstract Evidence suggests that increased level/aggregation of β-amyloid (Aβ) peptide, together with enhanced phosphorylation/aggregation of tau protein, play a critical role in the development of Alzheimer's disease (AD), the leading cause of dementia in the elderly. At present, AD diagnosis is based primarily on cognitive assessment, neuroimaging, and immunological assays to detect altered levels/deposition of Aβ peptides and tau protein. While measurement of Aβ and tau in the cerebrospinal fluid/blood can indicate disease status, neuroimaging of aggregated Aβ and tau protein in the brain using positron emission tomography (PET) enable to monitor the pathological changes in AD patients. With advancements in nanomedicine, several nanoparticles, apart from drug-delivery, have been used as a diagnostic agent to identify more accurately changes in AD patients. Recently, we reported that FDA approved native PLGA nanoparticles can interact with Aβ to inhibit its aggregation/toxicity in cellular and animal models of AD. Here, we reveal that fluorescence labelled native PLGA following acute intracerebellar injection can identify majority of the immunostained Aβ as well as Congo red labelled neuritic plaques in the cortex of 5xFAD mice. Labelling of plaques by PLGA is apparent at 1 h, peak around 3 h and then start declining by 24 h after injection. No fluorescent PLGA was detected in the cerebellum of 5xFAD mice or in any brain regions of wild-type control mice following injection. These results provide the very first evidence that native PLGA nanoparticles can be used as a novel nano-theragnostic agent in the treatment as well as diagnosis of AD pathology.
    MeSH term(s) Mice ; Animals ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; Plaque, Amyloid/metabolism ; Nanoparticles ; Brain/metabolism ; Disease Models, Animal ; Mice, Transgenic
    Chemical Substances Amyloid beta-Peptides ; tau Proteins
    Language English
    Publishing date 2023-07-10
    Publishing country England
    Document type Letter
    ZDB-ID 2100022-0
    ISSN 1477-3155 ; 1477-3155
    ISSN (online) 1477-3155
    ISSN 1477-3155
    DOI 10.1186/s12951-023-01957-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction: Detection of β-amyloid aggregates/plaques in 5xFAD mice by labelled native PLGA nanoparticles: implication in the diagnosis of Alzheimer's disease.

    Govindarajan, Karthivashan / Kar, Satyabrata

    Journal of nanobiotechnology

    2023  Volume 21, Issue 1, Page(s) 251

    Language English
    Publishing date 2023-08-03
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2100022-0
    ISSN 1477-3155 ; 1477-3155
    ISSN (online) 1477-3155
    ISSN 1477-3155
    DOI 10.1186/s12951-023-02009-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Administration of Kainic Acid Differentially Alters Astrocyte Markers and Transiently Enhanced Phospho-tau Level in Adult Rat Hippocampus.

    Dahal, Abhishek / Govindarajan, Karthivashan / Kar, Satyabrata

    Neuroscience

    2023  Volume 516, Page(s) 27–41

    Abstract: Kainic acid (KA), an analogue of the excitatory neurotransmitter glutamate, when administered systemically can trigger seizures and neuronal loss in a manner that mirrors the neuropathology of human mesial temporal lobe epilepsy (mTLE), which affects ∼50 ...

    Abstract Kainic acid (KA), an analogue of the excitatory neurotransmitter glutamate, when administered systemically can trigger seizures and neuronal loss in a manner that mirrors the neuropathology of human mesial temporal lobe epilepsy (mTLE), which affects ∼50 million people globally. Evidence suggests that changes in astrocytes which precede neuronal damage play an important role in the degeneration of neurons and/or development of seizures in TLE pathogenesis. Additionally, a role for microtubule associated tau protein, involved in various neurodegenerative diseases including Alzheimer's disease, has also been suggested in the development of seizure and/or neurodegeneration in TLE pathogenesis. At present, possible alterations of different subtypes of astrocytes and their association, if any, with tau protein in TLE remain unclear. In this study, we evaluated alterations of different subtypes of astrocytes and phospho-/cleaved-tau levels in KA-treated rat model of TLE. Our results reveal that levels/expression of various astrocyte markers such as GFAP, vimentin, S100B, Aldh1L1, but not GS, are increased in the hippocampus of KA-treated rats. The levels/expression of both A1(C3+) and A2(S100A10+)-like astrocytes are also increased in KA-treated rats. Concurrently, the total (Tau1 and Tau5) and phospho-tau (AT270 and PHF1) levels are transiently enhanced following KA administration. Furthermore, the level/expression of cleaved-tau, which is apparent in a subset of GFAP-, S100B- and A2-positive astrocytes, are increased in KA-treated rats. These results, taken together, suggest a differential role for various astrocytic subpopulations and tau protein in the development of seizure and/or loss of neurons in KA model of TLE and possibly in human mTLE pathogenesis.
    MeSH term(s) Humans ; Adult ; Rats ; Animals ; Kainic Acid ; Astrocytes/metabolism ; tau Proteins/metabolism ; Hippocampus/metabolism ; Seizures/metabolism ; Epilepsy, Temporal Lobe/metabolism ; Disease Models, Animal
    Chemical Substances Kainic Acid (SIV03811UC) ; tau Proteins
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 196739-3
    ISSN 1873-7544 ; 0306-4522
    ISSN (online) 1873-7544
    ISSN 0306-4522
    DOI 10.1016/j.neuroscience.2023.02.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mimosine functionalized gold nanoparticles (Mimo-AuNPs) suppress β-amyloid aggregation and neuronal toxicity

    Bibin G. Anand / Qi Wu / Govindarajan Karthivashan / Kiran P. Shejale / Sara Amidian / Holger Wille / Satyabrata Kar

    Bioactive Materials, Vol 6, Iss 12, Pp 4491-

    2021  Volume 4505

    Abstract: Evidence suggests that increased level/aggregation of beta-amyloid (Aβ) peptides initiate neurodegeneration and subsequent development of Alzheimer's disease (AD). At present, there is no effective treatment for AD. In this study, we reported the effects ...

    Abstract Evidence suggests that increased level/aggregation of beta-amyloid (Aβ) peptides initiate neurodegeneration and subsequent development of Alzheimer's disease (AD). At present, there is no effective treatment for AD. In this study, we reported the effects of gold nanoparticles surface-functionalized with a plant-based amino acid mimosine (Mimo-AuNPs), which is found to cross the blood-brain barrier, on the Aβ fibrillization process and toxicity. Thioflavin T kinetic assays, fluorescence imaging and electron microscopy data showed that Mimo-AuNPs were able to suppress the spontaneous and seed-induced Aβ1-42 aggregation. Spectroscopic studies, molecular docking and biochemical analyses further revealed that Mimo-AuNPs stabilize Aβ1-42 to remain in its monomeric state by interacting with the hydrophobic domain of Aβ1-42 (i.e., Lys16 to Ala21) there by preventing a conformational shift towards the β-sheet structure. Additionally, Mimo-AuNPs were found to trigger the disassembly of matured Aβ1-42 fibers and increased neuronal viability by reducing phosphorylation of tau protein and the production of oxyradicals. Collectively, these results reveal that the surface-functionalization of gold nanoparticles with mimosine can attenuate Aβ fibrillization and neuronal toxicity. Thus, we propose Mimo-AuNPs may be used as a potential treatment strategy towards AD-related pathologies.
    Keywords Alzheimer's disease ; β-amyloid aggregation ; Gold nanoparticles ; Mimosine ; Neuroprotection ; Materials of engineering and construction. Mechanics of materials ; TA401-492 ; Biology (General) ; QH301-705.5
    Subject code 500
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher KeAi Communications Co., Ltd.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in an acetaminophen-induced nephrotoxic mice model

    Govindarajan Karthivashan / Aminu Umar Kura / Palanisamy Arulselvan / Norhaszalina Md. Isa / Sharida Fakurazi

    PeerJ, Vol 4, p e

    2016  Volume 2127

    Abstract: N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the ... ...

    Abstract N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin—positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment. Therefore, MO leaf extract has demonstrated some ...
    Keywords Moringa oleifera ; Acetaminophen nephrotoxicity ; Serum biochemical markers ; Antioxidant enzymes ; Inflammatory cytokines ; Kidney histology ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2016-07-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Bioactive extract from moringa oleifera inhibits the pro-inflammatory mediators in lipopolysaccharide stimulated macrophages

    Masoumeh Tangestani Fard / Palanisamy Arulselvan / Govindarajan Karthivashan / Siti Khadijah Adam / Sharida Fakurazi

    Pharmacognosy Magazine, Vol 11, Iss 44, Pp 556-

    2015  Volume 563

    Abstract: Introduction: Inflammation is a well-known physiological response to protect the body against infection and restore tissue injury. Nevertheless, the chronic inflammation can trigger various inflammatory associated diseases/disorder. Moringa oleifera is a ...

    Abstract Introduction: Inflammation is a well-known physiological response to protect the body against infection and restore tissue injury. Nevertheless, the chronic inflammation can trigger various inflammatory associated diseases/disorder. Moringa oleifera is a widely grown plant in most tropical countries and it has been recognized traditionally for several medicinal benefits. Objectives: The objective of this study was to investigate the anti-inflammatory properties of M. oleifera extract on lipopolysaccharide (LPS) - stimulated macrophages. Materials and Methods: The anti-inflammatory effect of M. oleifera hydroethanolic bioactive leaves extracts was evaluated by assessing the inhibition of nitric oxide (NO) production during Griess reaction and the expression of pro-inflammatory mediators in macrophages. Results: Interestingly, we found that M. oleifera hydroethanolic bioactive leaves extract significantly inhibited the secretion of NO production and other inflammatory markers such as prostaglandin E 2 , tumor necrosis factor alpha, interleukin (IL)-6, and IL-1b. Meanwhile, the bioactive extract has induced the production of IL-10 in a dose-dependent manner. In addition, M. oleifera hydroethanolic bioactive leaves extract effectively suppressed the protein expression of inflammatory markers inducible NO synthase, cyclooxygenase-2, and nuclear factor kappa-light-chain-enhancer of activated B-cells p65 in LPS-induced RAW264.7 macrophages in a dose-dependent manner. Conclusion: These findings support the traditional use of M. oleifera plant as an effective treatment for inflammation associated diseases/disorders.
    Keywords Anti-inflammatory ; lipopolysaccharide ; Moringa oleifera ; pro-inflammatory ; RAW264.7 murine macrophage ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 616 ; 610
    Publishing date 2015-01-01T00:00:00Z
    Publisher Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Competing Role of Bioactive Constituents in Moringa oleifera Extract and Conventional Nutrition Feed on the Performance of Cobb 500 Broilers

    Govindarajan Karthivashan / Palanisamy Arulselvan / Abd. Razak Alimon / Intan Safinar Ismail / Sharida Fakurazi

    BioMed Research International, Vol

    2015  Volume 2015

    Abstract: The influence of Moringa oleifera (MO) leaf extract as a dietary supplement on the growth performance and antioxidant parameters was evaluated on broiler meat and the compounds responsible for the corresponding antioxidant activity were identified. 0.5%, ...

    Abstract The influence of Moringa oleifera (MO) leaf extract as a dietary supplement on the growth performance and antioxidant parameters was evaluated on broiler meat and the compounds responsible for the corresponding antioxidant activity were identified. 0.5%, 1.0%, and 1.5% w/v of MO leaf aqueous extracts (MOLE) were prepared, and nutritional feed supplemented with 0%, 0.5%, 1.0%, and 1.5% w/w of MO leaf meal (MOLM) extracts were also prepared and analysed for their in vitro antioxidant potential. Furthermore, the treated broiler groups (control (T1) and treatment (T2, T3, and T4)) were evaluated for performance, meat quality, and antioxidant status. The results of this study revealed that, among the broilers fed MOLM, the broilers fed 0.5% w/w MOLM (T2) exhibited enhanced meat quality and antioxidant status (P<0.05). However, the antioxidant activity of the MOLE is greater than that of the MOLM. The LC-MS/MS analysis of MOLM showed high expression of isoflavones and fatty acids from soy and corn source, which antagonistically inhibit the expression of the flavonoids/phenols in the MO leaves thereby masking its antioxidant effects. Thus, altering the soy and corn gradients in conventional nutrition feed with 0.5% w/w MO leaves supplement would provide an efficient and cost-effective feed supplement.
    Keywords Medicine ; R
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Limited
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Comparative Studies on Behavioral, Cognitive and Biomolecular Profiling of ICR, C57BL/6 and Its Sub-Strains Suitable for Scopolamine-Induced Amnesic Models

    Govindarajan Karthivashan / Shin-Young Park / Joon-Soo Kim / Duk-Yeon Cho / Palanivel Ganesan / Dong-Kug Choi

    International Journal of Molecular Sciences, Vol 18, Iss 8, p

    2017  Volume 1735

    Abstract: Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate ... ...

    Abstract Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.
    Keywords scopolamine ; amnesia ; cognition ; CREB/BDNF ; outbred ICR strains ; inbred C57BL/6 strains ; C57BL/6N ; C57BL/6J sub-strains ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Lipid Nanoparticles Improve the Uptake of α-Asarone Into the Brain Parenchyma: Formulation, Characterization, In Vivo Pharmacokinetics, and Brain Delivery.

    Ramalingam, Prakash / Ganesan, Palanivel / Prabakaran, D S / Gupta, Pardeep K / Jonnalagadda, Sriramakamal / Govindarajan, Karthivashan / Vishnu, Revuri / Sivalingam, Kalaiselvi / Sodha, Srushti / Choi, Dong-Kug / Ko, Young Tag

    AAPS PharmSciTech

    2020  Volume 21, Issue 8, Page(s) 299

    Abstract: Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily ... ...

    Abstract Treatment of brain-related diseases is one of the most strenuous challenges in drug delivery research due to numerous hurdles, including poor blood-brain barrier penetration, lack of specificity, and severe systemic toxicities. Our research primarily focuses on the delivery of natural therapeutic compound, α-asarone, for the treatment of brain-related diseases. However, α-asarone has poor aqueous solubility, bioavailability, and stability, all of which are critical issues that need to be addressed. This study aims at formulating a lipid nanoparticulate system of α-asarone (A-LNPs) that could be used as a brain drug delivery system. The physicochemical, solid-state properties, stability, and in vitro and in vivo studies of the A-LNPs were characterized. The release of α-asarone from the A-LNPs was prolonged and sustained. After intravenous administration of A-LNPs or free α-asarone, significantly higher levels of α-asarone from the A-LNPs were detected in murine plasma and brain parenchyma fractions, confirming the ability of A-LNPs to not only maintain a therapeutic concentration of α-asarone in the plasma, but also transport α-asarone across the blood-brain barrier. These findings confirm that lipid nanoparticulate systems enable penetration of natural therapeutic compound α-asarone through the blood-brain barrier and may be a candidate for the treatment of brain-related diseases.
    MeSH term(s) Administration, Intravenous ; Animals ; Anisoles/pharmacokinetics ; Biological Availability ; Biological Transport ; Blood-Brain Barrier ; Brain/metabolism ; Lipids/chemistry ; Mice ; Nanoparticles/chemistry ; Tissue Distribution
    Chemical Substances Anisoles ; Lipids ; asarone
    Language English
    Publishing date 2020-11-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2052070-0
    ISSN 1530-9932 ; 1530-9932
    ISSN (online) 1530-9932
    ISSN 1530-9932
    DOI 10.1208/s12249-020-01832-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Antineuroinflammatory Activities and Neurotoxicological Assessment of Curcumin Loaded Solid Lipid Nanoparticles on LPS-Stimulated BV-2 Microglia Cell Models

    Palanivel Ganesan / Byungwook Kim / Prakash Ramalingam / Govindarajan Karthivashan / Vishnu Revuri / Shinyoung Park / Joon Soo Kim / Young Tag Ko / Dong-Kug Choi

    Molecules, Vol 24, Iss 6, p

    2019  Volume 1170

    Abstract: Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood–brain barrier and its rapid metabolism during circulation, which decreases its ... ...

    Abstract Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood–brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous system. The bioavailability and potential of curcumin can be improved by using a nanodelivery system, which includes solid lipid nanoparticles. Curcumin-loaded solid lipid nanoparticles (SLCN) were efficiently developed to have a particle size of about 86 nm and do not exhibit any toxicity in the endothelial brain cells. Furthermore, the curcumin-loaded solid lipid nanoparticles (SLCN) were studied to assess their efficacy in BV-2 microglial cells against LPS-induced neuroinflammation. The SLCN showed a higher inhibition of nitric oxide (NO) production compared to conventional curcumin in a dose-dependent manner. Similarly, the mRNA and proinflammatory cytokine levels were also reduced in a dose-dependent manner when compared to those with free curcumin. Thus, SLCN could be a potential delivery system for curcumin to treat microglia-mediated neuroinflammation.
    Keywords lipopolysaccharide ; solid lipid nanoparticle ; curcumin ; antineuroinflammation ; toxicity ; SEM ; Organic chemistry ; QD241-441
    Subject code 500
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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