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Book ; Online ; E-Book: MicroRNA in Human Infectious Diseases

Prajapati, Vijay Kumar / Ojha, Rupal

2024

Language	English
Size	1 online resource (346 pages)
Edition	1st ed.
Publisher	Elsevier Science & Technology
Publishing place	San Diego
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	0-323-99662-0 ; 9780323996617 ; 978-0-323-99662-4 ; 0323996612
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Design of inhibitor peptide sequences based on the interfacial knowledge of the protein G-IgG crystallographic complex and their binding studies with IgG.

Tanwar, Neetu / Ojha, Rupal / Aggarwal, Soumya / Prajapati, Vijay Kumar / Munde, Manoj

European biophysics journal : EBJ

2024 Volume 53, Issue 3, Page(s) 159–170

Abstract: Protein-protein interactions (PPI) have emerged as valuable targets in medicinal chemistry due to their key roles in important biological processes. The modulation of PPI by small peptides offers an excellent opportunity to develop drugs against human ... ...

Abstract	Protein-protein interactions (PPI) have emerged as valuable targets in medicinal chemistry due to their key roles in important biological processes. The modulation of PPI by small peptides offers an excellent opportunity to develop drugs against human diseases. Here, we exploited the knowledge of the binding interface of the IgG-protein G complex (PDB:1FCC) for designing peptides that can inhibit these complexes. Herein, we have designed several closely related peptides, and the comparison of results from experiments and computational studies indicated that all the peptides bind close to the expected binding site on IgG and the complexes are stable. A minimal sequence consisting of 11 amino acids (P5) with binding constants in the range of 100 nM was identified. We propose that the main affinity differences across the series of peptides arose from the presence of polar amino acid residues. Further, the molecular dynamic studies helped to understand the dynamic properties of complexes in terms of flexibility of residues and structural stability at the interface. The ability of P5 to compete with the protein G in recognizing IgG can help in the detection and purification of antibodies. Further, it can serve as a versatile tool for a better understanding of protein-protein interactions.
MeSH term(s)	Humans ; Peptides/chemistry ; Amino Acid Sequence ; Binding Sites ; Amino Acids/metabolism ; Immunoglobulin G/chemistry ; Immunoglobulin G/metabolism ; Protein Binding ; Thermodynamics
Chemical Substances	Peptides ; Amino Acids ; Immunoglobulin G
Language	English
Publishing date	2024-03-17
Publishing country	Germany
Document type	Journal Article
ZDB-ID	283671-3
ISSN	1432-1017 ; 0175-7571
ISSN (online)	1432-1017
ISSN	0175-7571
DOI	10.1007/s00249-024-01704-0
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Article ; Online: Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity.

Ojha, Rupal / Prajapati, Vijay Kumar

Journal of cellular physiology

2021 Volume 236, Issue 12, Page(s) 8020–8034

Abstract: Vaccination is a significant advancement or preventative strategy for controlling the spread of various severe infectious and noninfectious diseases. The purpose of vaccination is to stimulate or activate the immune system by injecting antigens, i.e., ... ...

Abstract	Vaccination is a significant advancement or preventative strategy for controlling the spread of various severe infectious and noninfectious diseases. The purpose of vaccination is to stimulate or activate the immune system by injecting antigens, i.e., either whole microorganisms or using the pathogen's antigenic part or macromolecules. Over time, researchers have made tremendous efforts to reduce vaccine side effects or failure by developing different strategies combining with immunoinformatic and molecular biology. These newly designed vaccines are composed of single or several antigenic molecules derived from a pathogenic organism. Although, whole-cell vaccines are still in use against various diseases but due to their ineffectiveness, other vaccines like DNA-based, RNA-based, and protein-based vaccines, with the addition of immunostimulatory agents, are in the limelight. Despite this, many researchers escape the most common fundamental phenomenon of protein posttranslational modifications during the development of vaccines, which regulates protein functional behavior, evokes immunogenicity and stability, etc. The negligence about post translational modification (PTM) during vaccine development may affect the vaccine's efficacy and immune responses. Therefore, it becomes imperative to consider these modifications of macromolecules before finalizing the antigenic vaccine construct. Here, we have discussed different types of posttranslational/transcriptional modifications that are usually considered during vaccine construct designing: Glycosylation, Acetylation, Sulfation, Methylation, Amidation, SUMOylation, Ubiquitylation, Lipidation, Formylation, and Phosphorylation. Based on the available research information, we firmly believe that considering these modifications will generate a potential and highly immunogenic antigenic molecule against communicable and noncommunicable diseases compared to the unmodified macromolecules.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; Animals ; Antigens/immunology ; Humans ; Immunogenicity, Vaccine/immunology ; Vaccination/methods ; Vaccine Development ; Vaccines/immunology
Chemical Substances	Adjuvants, Immunologic ; Antigens ; Vaccines
Language	English
Publishing date	2021-06-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.30483
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Article ; Online: Cloning, expression and in vitro validation of chimeric multi epitope vaccine candidate against visceral leishmaniasis infection.

Ojha, Rupal / Chand, Kailash / Vellingiri, Balachandar / Prajapati, Vijay Kumar

Life sciences

2023 Volume 323, Page(s) 121689

Abstract: Visceral Leishmaniasis or Kala-Azar is one of the most severe and deadly neglected tropical disease caused by the Leishmania parasite. A few number of vaccines are going through different phases in clinical trial but failing of these vaccines in ... ...

Abstract	Visceral Leishmaniasis or Kala-Azar is one of the most severe and deadly neglected tropical disease caused by the Leishmania parasite. A few number of vaccines are going through different phases in clinical trial but failing of these vaccines in successive phase trial or less efficacy, urge to develop highly immunogenic and cost-effective treatment to get rid of deadly VL. This study focuses on the development of more potent vaccine candidate against VL. The recombinant vaccine candidate LeiSp was expressed in Pichia pastoris, followed by purification and characterization. The purified protein was also tested for any post-translation modification, which favors being a potent immunogenic candidate. Further, the expression modulation of different pro-inflammatory and anti-inflammatory cytokines was evaluated in THP1 cell lines. A significant upregulation in the expression of pro-inflammatory cytokines while no significant changes were observed in the expression of anti-inflammatory cytokines. The impact of recombinant vaccine protein candidates in infected conditions were determined. Here, upon treatment with chimeric vaccine protein candidate, we observed a considerable recovery in the expression level of pro-inflammatory cytokines, which were downregulated upon infection alone. In addition to this, we found a significant decrease in the expression of anti-inflammatory cytokines, which were upregulated during infection alone. We further validated our findings in infected hPBMCs and observed similar expression modulation of pro-inflammatory and anti-inflammatory cytokines with and without treatment. Thus, the present study indicates that the chimeric LeiSp protein which was designed using bioinformatics approaches shows a potential inductive efficacy for pro-inflammatory cytokines in Leishmania-infected cells.
MeSH term(s)	Animals ; Mice ; Leishmaniasis, Visceral/prevention & control ; Epitopes ; Leishmaniasis Vaccines ; Leishmania ; Cytokines/metabolism ; Vaccines, Synthetic ; Recombinant Proteins/genetics ; Cloning, Molecular ; Mice, Inbred BALB C
Chemical Substances	Epitopes ; Leishmaniasis Vaccines ; Cytokines ; Vaccines, Synthetic ; Recombinant Proteins
Language	English
Publishing date	2023-04-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121689
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Article ; Online: Cloning, expression and in vitro validation of chimeric multi epitope vaccine candidate against visceral leishmaniasis infection

Ojha, Rupal / Chand, Kailash / Vellingiri, Balachandar / Prajapati, Vijay Kumar

Life Sciences. 2023 June, v. 323 p.121689-

2023

Abstract	Visceral Leishmaniasis or Kala-Azar is one of the most severe and deadly neglected tropical disease caused by the Leishmania parasite. A few number of vaccines are going through different phases in clinical trial but failing of these vaccines in successive phase trial or less efficacy, urge to develop highly immunogenic and cost-effective treatment to get rid of deadly VL. This study focuses on the development of more potent vaccine candidate against VL. The recombinant vaccine candidate LeiSp was expressed in Pichia pastoris, followed by purification and characterization. The purified protein was also tested for any post-translation modification, which favors being a potent immunogenic candidate. Further, the expression modulation of different pro-inflammatory and anti-inflammatory cytokines was evaluated in THP1 cell lines. A significant upregulation in the expression of pro-inflammatory cytokines while no significant changes were observed in the expression of anti-inflammatory cytokines. The impact of recombinant vaccine protein candidates in infected conditions were determined. Here, upon treatment with chimeric vaccine protein candidate, we observed a considerable recovery in the expression level of pro-inflammatory cytokines, which were downregulated upon infection alone. In addition to this, we found a significant decrease in the expression of anti-inflammatory cytokines, which were upregulated during infection alone. We further validated our findings in infected hPBMCs and observed similar expression modulation of pro-inflammatory and anti-inflammatory cytokines with and without treatment. Thus, the present study indicates that the chimeric LeiSp protein which was designed using bioinformatics approaches shows a potential inductive efficacy for pro-inflammatory cytokines in Leishmania-infected cells.
Keywords	Komagataella pastoris ; Leishmania ; bioinformatics ; clinical trials ; cost effectiveness ; cytokines ; epitopes ; parasites ; post-translational modification ; recombinant vaccines ; tropical diseases ; visceral leishmaniasis ; Leishmaniasis ; Multiepitope vaccine ; Immune response
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121689
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Multi-pathogen based chimeric vaccine to fight against COVID-19 and concomitant coinfections.

Ojha, Rupal / Singh, Satyendra / Gupta, Nidhi / Kumar, Ketan / Padhi, Aditya K / Prajapati, Vijay Kumar

Biotechnology letters

2023 Volume 45, Issue 7, Page(s) 779–797

Abstract: Background: COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with ... ...

Abstract	Background: COVID-19 has proved to be a fatal disease of the year 2020, due to which thousands of people globally have lost their lives, and still, the infection cases are at a high rate. Experimental studies suggested that SARS-CoV-2 interacts with various microorganisms, and this coinfection is accountable for the augmentation of infection severity. Methods and results: In this study, we have designed a multi-pathogen vaccine by involving the immunogenic proteins from S. pneumonia, H. influenza, and M. tuberculosis, as they are dominantly associated with SARS-CoV-2. A total of 8 antigenic protein sequences were selected to predict B-cell, HTL, and CTL epitopes restricted to the most prevalent HLA alleles. The selected epitopes were antigenic, non-allergenic, and non-toxic and were linked with adjuvant and linkers to make the vaccine protein more immunogenic, stable, and flexible. The tertiary structure, Ramachandran plot, and discontinuous B-cell epitopes were predicted. Docking and MD simulation study has shown efficient binding of the chimeric vaccine with the TLR4 receptor. Conclusion: The in silico immune simulation analysis has shown a high level of cytokines and IgG after a three-dose injection. Hence, this strategy could be a better way to decrease the disease's severity and could be used as a weapon to prevent this pandemic.
MeSH term(s)	Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; COVID-19 Vaccines ; Coinfection ; Viral Vaccines ; Epitopes, T-Lymphocyte/genetics ; Molecular Docking Simulation ; Vaccines, Subunit ; Epitopes, B-Lymphocyte/genetics ; Epitopes, B-Lymphocyte/chemistry ; Computational Biology/methods
Chemical Substances	COVID-19 Vaccines ; Viral Vaccines ; Epitopes, T-Lymphocyte ; Vaccines, Subunit ; Epitopes, B-Lymphocyte
Language	English
Publishing date	2023-05-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	423853-9
ISSN	1573-6776 ; 0141-5492
ISSN (online)	1573-6776
ISSN	0141-5492
DOI	10.1007/s10529-023-03380-0
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Article ; Online: Vaccinomics strategy to concoct a promising subunit vaccine for visceral leishmaniasis targeting sandfly and leishmania antigens.

Ojha, Rupal / Pandey, Rajan Kumar / Prajapati, Vijay Kumar

International journal of biological macromolecules

2020 Volume 156, Page(s) 548–557

Abstract: Visceral leishmaniasis (VL) has been declared as one of the most severely neglected tropical diseases by the World Health Organization report 2017. Cumulative incidences of treatment failure and drug resistance, demanding a potential treatment and ... ...

Abstract	Visceral leishmaniasis (VL) has been declared as one of the most severely neglected tropical diseases by the World Health Organization report 2017. Cumulative incidences of treatment failure and drug resistance, demanding a potential treatment and preventive strategy for VL. In this study, we have devised a multi-epitope vaccine by targeting sandfly saliva and parasite-derived membrane and secretory antigens. We have predicted the immunogenic B-cell, HTL, and CTL epitopes from all the selected protein sequences. The epitopes were then linked to the spacer sequences for providing stability and flexibility, and the construct was linked with a synthetic TLR-4 agonist namely RS09 as an adjuvant. The 3D structure of vaccine was modelled, refined and validated by generating a Ramachandran plot. Later, molecular docking was performed between the TLR-4 receptor and vaccine. The obtained docked complex was then checked for their stability by performing MD simulation. The immune dynamics simulation was done to check the probable immune response generated when the host will be exposed to the vaccine candidate. This novel vaccine strategy will provide functional and mechanistic evidence on parasite and vector-derived epitopes that could activate B- and T-cells and potentially elicit a long-lasting memory cell response.
MeSH term(s)	Animals ; Antigens, Protozoan/chemistry ; Antigens, Protozoan/immunology ; Chemical Phenomena ; Epitopes, B-Lymphocyte/immunology ; Epitopes, T-Lymphocyte/immunology ; Host-Pathogen Interactions/immunology ; Immunogenicity, Vaccine ; Leishmania/immunology ; Leishmaniasis Vaccines/immunology ; Leishmaniasis, Visceral/prevention & control ; Molecular Conformation ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Psychodidae/immunology ; Structure-Activity Relationship ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; Toll-Like Receptor 4/chemistry ; Toll-Like Receptor 4/metabolism ; Vaccines, Subunit/immunology ; Vaccinology/methods
Chemical Substances	Antigens, Protozoan ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Leishmaniasis Vaccines ; Toll-Like Receptor 4 ; Vaccines, Subunit
Language	English
Publishing date	2020-04-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2020.04.097
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Article ; Online: Designing of a bispecific antibody against SARS-CoV-2 spike glycoprotein targeting human entry receptors DPP4 and ACE2.

Ojha, Rupal / Gurjar, Kiran / Ratnakar, Tadi Sai / Mishra, Amit / Prajapati, Vijay Kumar

Human immunology

2022 Volume 83, Issue 4, Page(s) 346–355

Abstract: COVID-19 originated in Wuhan city, China, in 2019 erupted a global pandemic that had put down nearly 3 million lives and hampered the socio-economic conditions of all nations. Despite the available treatments, this disease is not being controlled totally ...

Abstract	COVID-19 originated in Wuhan city, China, in 2019 erupted a global pandemic that had put down nearly 3 million lives and hampered the socio-economic conditions of all nations. Despite the available treatments, this disease is not being controlled totally and spreading swiftly. The deadly virus commences infection by hACE2 receptor and its co-receptors (DPP4) engagement with the viral spike protein in the lung alveolar epithelial cells, indicating a primary therapeutic target. The current research attempts to design an in-silico Bispecific antibody (BsAb) against viral spike glycoprotein and DPP4 receptors. Regdanvimab and Begelomab were identified to block the D614G mutated spike glycoprotein of SARS-CoV-2 and host DPP4 receptor, respectively. The designed BsAb was modified by using KIH (Knobs into Holes) and CrossMAb techniques to prevent heavy chain and light chain mispairings. Following the modifications, the site-specific molecular docking studies were performed, revealing a relatively higher binding affinity of BsAb with spike glycoprotein and DPP4 co-receptor than control BsAb. Also, for blocking the primary entry receptor, hACE2, an anti-viral peptide was linked to the Fc region of BsAb that blocks the hACE2 receptor by linker cleavage inside the infected host. Thus, the designed BsAb and anti-viral peptide therapy could be a promising triumvirate way to obstruct the viral entry by blocking the receptor engagement.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; COVID-19 ; Dipeptidyl Peptidase 4/metabolism ; Humans ; Immunoglobulin G ; Molecular Docking Simulation ; Protein Binding ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; DPP4 protein, human (EC 3.4.14.5) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; regdanvimab (I0BGE6P6I6)
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	801524-7
ISSN	1879-1166 ; 0198-8859
ISSN (online)	1879-1166
ISSN	0198-8859
DOI	10.1016/j.humimm.2022.01.004
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Article: Unveiling the Molecular Footprint: Proteome-Based Biomarkers for Alzheimer's Disease.

Jain, Mukul / Dhariwal, Rupal / Patil, Nil / Ojha, Sandhya / Tendulkar, Reshma / Tendulkar, Mugdha / Dhanda, Parmdeep Singh / Yadav, Alpa / Kaushik, Prashant

Proteomes

2023 Volume 11, Issue 4

Abstract: Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Early and accurate diagnosis of AD is crucial for implementing timely interventions and developing effective therapeutic ... ...

Abstract	Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Early and accurate diagnosis of AD is crucial for implementing timely interventions and developing effective therapeutic strategies. Proteome-based biomarkers have emerged as promising tools for AD diagnosis and prognosis due to their ability to reflect disease-specific molecular alterations. There is of great significance for biomarkers in AD diagnosis and management. It emphasizes the limitations of existing diagnostic approaches and the need for reliable and accessible biomarkers. Proteomics, a field that comprehensively analyzes the entire protein complement of cells, tissues, or bio fluids, is presented as a powerful tool for identifying AD biomarkers. There is a diverse range of proteomic approaches employed in AD research, including mass spectrometry, two-dimensional gel electrophoresis, and protein microarrays. The challenges associated with identifying reliable biomarkers, such as sample heterogeneity and the dynamic nature of the disease. There are well-known proteins implicated in AD pathogenesis, such as amyloid-beta peptides, tau protein, Apo lipoprotein E, and clusterin, as well as inflammatory markers and complement proteins. Validation and clinical utility of proteome-based biomarkers are addressing the challenges involved in validation studies and the diagnostic accuracy of these biomarkers. There is great potential in monitoring disease progression and response to treatment, thereby aiding in personalized medicine approaches for AD patients. There is a great role for bioinformatics and data analysis in proteomics for AD biomarker research and the importance of data preprocessing, statistical analysis, pathway analysis, and integration of multi-omics data for a comprehensive understanding of AD pathophysiology. In conclusion, proteome-based biomarkers hold great promise in the field of AD research. They provide valuable insights into disease mechanisms, aid in early diagnosis, and facilitate personalized treatment strategies. However, further research and validation studies are necessary to harness the full potential of proteome-based biomarkers in clinical practice.
Language	English
Publishing date	2023-10-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720995-7
ISSN	2227-7382
ISSN	2227-7382
DOI	10.3390/proteomes11040033
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Article ; Online: Febrifugine dihydrochloride as a new oral chemotherapeutic agent against visceral leishmaniasis infection.

Pandey, Rajan Kumar / Ojha, Rupal / Devender, Moodu / Sebastian, Prince / Namdeo, Madhulika / Kumbhar, Bajarang Vasant / Sundar, Shyam / Maurya, Radheshyam / Prajapati, Vijay Kumar

Experimental parasitology

2022 Volume 236-237, Page(s) 108250

Abstract: Visceral leishmaniasis (VL) is the deadliest form of leishmaniasis without a safer treatment option. This study implies drug repurposing to find a novel antileishmanial compound, namely febrifugine dihydrochloride (FFG) targeting Leishmania antioxidant ... ...

Abstract	Visceral leishmaniasis (VL) is the deadliest form of leishmaniasis without a safer treatment option. This study implies drug repurposing to find a novel antileishmanial compound, namely febrifugine dihydrochloride (FFG) targeting Leishmania antioxidant system. Starting with virtual screening revealed the high binding affinity and lead likeness of FFG against the trypanothione reductase (TR) enzyme of Leishmania donovani, followed by experimental validation. The promastigotes inhibition assay gave the IC50 concentration of FFG and Miltefosine (positive control) as 7.16 ± 1.39 nM and 11.41 ± 0.29 μM, respectively. Their CC
MeSH term(s)	Animals ; Antiprotozoal Agents/therapeutic use ; Antiprotozoal Agents/toxicity ; Cytokines/metabolism ; Leishmania donovani ; Leishmaniasis, Visceral/parasitology ; Mice ; Mice, Inbred BALB C ; Piperidines ; Quinazolines
Chemical Substances	Antiprotozoal Agents ; Cytokines ; Piperidines ; Quinazolines ; febrifugine (89UWD0FH2I)
Language	English
Publishing date	2022-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	391089-1
ISSN	1090-2449 ; 0014-4894
ISSN (online)	1090-2449
ISSN	0014-4894
DOI	10.1016/j.exppara.2022.108250
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