| 1. |
- Sharma, Vinay, et al.
(författare)
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Expression, purification, characterization and in silico analysis of newly isolated hydrocarbon degrading bleomycin resistance dioxygenase
- 2020
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Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 47:1, s. 533-544
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Tidskriftsartikel (refereegranskat)abstract
- In the present investigation, we report cloning, expression, purification and characterization of a novel Bleomycin Resistance Dioxygenase (BRPD). His-tagged fusion protein was purified to homogeneity using Ni-NTA affinity chromatography, yielding 1.2 mg of BRPD with specific activity of 6.25 U mg−1 from 600 ml of E. coli culture. Purified enzyme was a dimer with molecular weight ~ 26 kDa in SDS-PAGE and ~ 73 kDa in native PAGE analysis. The protein catalyzed breakdown of hydrocarbon substrates, including catechol and hydroquinone, in the presence of metal ions, as characterized via spectrophotometric analysis of the enzymatic reactions. Bleomycin binding was proven using the EMSA gel retardation assay, and the putative bleomycin binding site was further determined by in silico analysis. Molecular dynamic simulations revealed that BRPD attains octahedral configuration in the presence of Fe2+ ion, forming six co-ordinate complexes to degrade hydroquinone-like molecules. In contrary, in the presence of Zn2+ ion BRPD adopts tetrahedral configuration, which enables degradation of catechol-like molecules.
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| 2. |
- Verma, Swati, et al.
(författare)
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Cloning, Characterization, and Structural Modeling of an Extremophilic Bacterial Lipase Isolated from Saline Habitats of the Thar Desert
- 2020
-
Ingår i: Applied Biochemistry and Biotechnology. - : Springer. - 0273-2289 .- 1559-0291. ; 192, s. 557-572
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Tidskriftsartikel (refereegranskat)abstract
- Lipases have a characteristic folding pattern of α/β-hydrolase with mostly parallel β-sheets, flanked on both sides by α-helixes in the structure. The active site is formed by a catalytic triad (serine, aspartic/glutamic acid, and histidine), which is highly conserved. In this study, we have used an integrated experimental and computational approach to identify the extremophilic microbial lipases from the saline habitats of the Thar Desert of Rajasthan. Lipase-producing bacteria were screened and a few samples showed significant lipase activity in both quantitative and qualitative experiments. 16S rRNA sequence analysis of the isolate F1 showed that its sequence is quite similar to that of Bacillus licheniformis and Bacillus haynesii, indicating that this isolate belongs to a new subspecies of Bacillus. The isolate F7 showed maximum sequence identity with Bacillus tequilensis strain 10b. The isolate F7 sequence analysis provided a clear testimony that it can be a new strain of Bacillus tequilensis. The F7 lipase exhibited optimal activity at 60 °C and pH 9. Structural modeling of the F7 lipase revealed that it has a highly conserved alpha/beta hydrolase fold at the sequence and structural level except for the N-terminal region. Interestingly, residue Glu128 was different from the template structure and showed the hydrogen bonding between the side chain of Glu128 and side chains of Asn35 and Gln152 amino acids. Besides, this amino acid also showed salt bridge interaction between Glu128--Lys101. These interactions may be assisting in preserving the stability and activity of lipase at high temperatures and in alkaline pH conditions. The information gathered from this investigation will guide in the rational designing of new more potential extremophilic lipase.
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| 3. |
- Verma, Suresh K., et al.
(författare)
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The posterity of Zebrafish in paradigm of in vivo molecular toxicological profiling
- 2024
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier. - 0753-3322 .- 1950-6007. ; 171
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Forskningsöversikt (refereegranskat)abstract
- The aggrandised advancement in utility of advanced day-to-day materials and nanomaterials has raised serious concern on their biocompatibility with human and other biotic members. In last few decades, understanding of toxicity of these materials has been given the centre stage of research using many in vitro and in vivo models. Zebrafish (Danio rerio), a freshwater fish and a member of the minnow family has garnered much attention due to its distinct features, which make it an important and frequently used animal model in various fields of embryology and toxicological studies. Given that fertilization and development of zebrafish eggs take place externally, they serve as an excellent model organism for studying early developmental stages. Moreover, zebrafish possess a comparable genetic composition to humans and share almost 70% of their genes with mammals. This particular model organism has become increasingly popular, especially for developmental research. Moreover, it serves as a link between in vitro studies and in vivo analysis in mammals. It is an appealing choice for vertebrate research, when employing high-throughput methods, due to their small size, swift development, and relatively affordable laboratory setup. This small vertebrate has enhanced comprehension of pathobiology and drug toxicity. This review emphasizes on the recent developments in toxicity screening and assays, and the new insights gained about the toxicity of drugs through these assays. Specifically, the cardio, neural, and, hepatic toxicology studies inferred by applications of nanoparticles have been highlighted.
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| 4. |
- Ahmed, Ajaj, et al.
(författare)
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Evaluation of Thar Desert bacterial lipases for catalytic efficiencies and biodiesel production potentials
- 2023
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Ingår i: Biologia. - : Springer Nature. - 0006-3088 .- 1336-9563. ; 78:4, s. 1187-1197
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Tidskriftsartikel (refereegranskat)abstract
- The present work describes the screening of thermotolerant bacteria isolated from Thar Desert environmental samples for lipase activity and their catalytic efficiencies, such as tolerance to extreme pHs, temperatures, and organic solvents, and efficiency to synthesize biodiesel from waste cooking oils. The selected lipases were thermos-alkaliphilic in nature showing good activity at higher temperatures and in the alkaline pH range with optimal activity at 45 °C and pH 8 or 9. The lipases efficiently converted oils to biodiesel (fatty acid methyl ester), giving up to 78% conversion under specific reaction conditions. The enzyme (lipase) mediated biodiesel production will soon offer an eco-friendly and sustainable energy source for automobiles and industrial applications. The thermos-alkaliphilic properties of these lipases along with their efficiency to produce fatty acid methyl ester from waste cooking oil and methanol as well as other prospective applications, make them potential candidates for biodiesel production and other prospective applications such as the synthesis of flavor and fragrance esters and remediation of various environmental pollutants.
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| 5. |
- Chinnadurai, Raj Kumar, et al.
(författare)
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Current research status of anti-cancer peptides : Mechanism of action, production, and clinical applications
- 2023
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Ingår i: Biomedicine and Pharmacotherapy. - : Elsevier BV. - 0753-3322 .- 1950-6007. ; 164
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Forskningsöversikt (refereegranskat)abstract
- The escalating rate of cancer cases, together with treatment deficiencies and long-term side effects of currently used cancer drugs, has made this disease a global burden of the 21st century. The number of breast and lung cancer patients has sharply increased worldwide in the last few years. Presently, surgical treatment, radiotherapy, chemotherapy, and immunotherapy strategies are used to cure cancer, which cause severe side effects, toxicities, and drug resistance. In recent years, anti-cancer peptides have become an eminent therapeutic strategy for cancer treatment due to their high specificity and fewer side effects and toxicity. This review presents an updated overview of different anti-cancer peptides, their mechanisms of action and current production strategies employed for their manufacture. In addition, approved and under clinical trials anti-cancer peptides and their applications have been discussed. This review provides updated information on therapeutic anti-cancer peptides that hold great promise for cancer treatment in the near future.
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| 6. |
- Kaur, Ramanpreet, et al.
(författare)
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Structural and functional insights about unique extremophilic bacterial lipolytic enzyme from metagenome source
- 2020
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 152, s. 593-604
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Tidskriftsartikel (refereegranskat)abstract
- In the present investigation, a lipid hydrolyzing gene RPK01 was cloned from metagenome source of hot spring. Expression and purification of recombinant protein revealed single purified protein band of similar to 24 KDa on 12% SDS-PAGE, and is well corroborated with the deduced molecular weight of protein as calculated from its amino acid sequence. The purified protein displayed high activity towards short chain fatty acids and was found to be completely stable at 30 degrees C till 3h, it further retained similar to 40% activity at 50 degrees C and 60 degrees C temperature till 3h. Additionally, the pH stability assay showed its functionality in broad range of pH, with maximum stability observed at pH 2.0, it decreases from pH 4.0 to pH 12.0, and nearly showed 40% activity in these pH values. Both circular dichroism and intrinsic Trp fluorescence studies revealed conformational stability of protein structure at wide range of temperature and pH. Enzyme activity enhances in presence of non-ionic surfactants like Tween 20 and TritonX-100. Further, inhibitors of the active site residues including PMSF and DEPC alone were unable to inhibit enzyme activity, while cumulative presence of calcium and inhibitors reduces enzyme activity to 90%, indicating conformational changes in the protein. Molecular simulation dynamics analysis revealed a calcium binding site near the lid helix of this protein(Asn75-Ile80).
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| 7. |
- Meghwanshi, Gautam Kumar, et al.
(författare)
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Enzymes for pharmaceutical and therapeutic applications
- 2020
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Ingår i: Biotechnology and applied biochemistry. - : John Wiley & Sons. - 0885-4513 .- 1470-8744. ; 67:4, s. 586-601
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Forskningsöversikt (refereegranskat)abstract
- Enzymes are highly efficient and selective biocatalysts, present in the living beings. They exist in enormous varieties in terms of the types of reactions catalyzed by them for instance oxidation-reduction, group transfers within the molecules or between the molecules, hydrolysis, isomerization, ligation, bond cleavage, and bond formation. Besides, enzyme based catalyses are performed with much higher fidelity, under mild reaction conditions and are highly efficient in terms of number of steps, giving them an edge over their chemical counter parts. The unique characteristics of enzymes makes them highly applicable fora number of chemical transformation reactions in pharmaceutical industries, such as group protection and deprotection, selective acylation and deacylation, selective hydrolysis, deracemization, kinetic resolution of racemic mixtures, esterification, transesterification, and many others. In this review, an overview of the enzymes, their production and their applications in pharmaceutical syntheses and enzyme therapies are presented with diagrams, reaction schemes and table for easy understanding of the readers.
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| 8. |
- Rabiee, Navid, et al.
(författare)
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Green Biomaterials : fundamental principles
- 2023
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Ingår i: Green Biomaterials. - : Taylor & Francis. - 2993-4168. ; 1:1, s. 1-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Bhattacharjee, Rahul, et al.
(författare)
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Synergy of nanocarriers with CRISPR-Cas9 in an emerging technology platform for biomedical appliances : Current insights and perspectives
- 2022
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 224
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Tidskriftsartikel (refereegranskat)abstract
- Genetic editing technologies have emerged as a potential therapeutic tool in various biomedical fields owing to their applications against cancer, neurological diseases, diabetes, autoimmune disorder, muscu-lar dystrophy, bacterial infections (AMR), and cardiovascular diseases. CRISPR is one such valuable genetic editing tool with extensive therapeutic appliances but with a major challenge in terms of deliv-ery. Herein, we have strived to exploit a synergy of nanocarriers and CRISPR against the aforementioned diseases for their medical applications and explicated their clinical significance including the enhanced delivery via endosomal escape and environmental factors such as light, pH, and stimuli. In addition to highlighting the delivery strategies of nano-carriers for CRISPR and their characterization, we have expounded on the reliant factor of the CRISPR-Cas Complex.
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| 10. |
- Chauhan, Shakti, et al.
(författare)
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Designing peptide-based vaccine candidates for Plasmodium falciparum erythrocyte binding antigen 175
- 2020
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Ingår i: Biologicals (Print). - : Elsevier. - 1045-1056 .- 1095-8320. ; 67, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- Plasmodium falciparum leads to a virulent form of malaria. Progress has been achieved in understanding the mechanisms involved in the malarial infection, still there is no effective vaccine to prevent severe infection. An effective vaccine against malaria should be one which can induce immune responses against multiple epitopes in the context of predominantly occurring HLA alleles. In this study, an integrated approach was employed to identify promiscuous peptides of a well-defined sequence of erythrocyte binding antigen-175 and promiscuous peptides for HLA alleles were designed using bioinformatics tools. A peptide with 15 amino acids (ILAIAIYESRILKRK) was selected based on its high binding affinity score and synthesized. This promiscuous peptide was used as stimulating antigen in lymphoproliferative responses to evaluate the cellular immune response. It was observed this peptide evokes lymphoproliferative and cytokine responses in individuals naturally exposed to the malaria parasite. The intensity of PBMCs proliferation was observed to be higher in sera obtained from P. falciparum exposed as compared to unexposed healthy individuals, suggesting earlier recognition of peptide of this region by T cells. Furthermore, the binding mode of HLA–peptide complex and their interaction may lead to a rational and selective peptide-based vaccine candidate design approach which can be used as a malaria prophylaxis.
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| 11. |
- Chinnadurai, Raj Kumar, et al.
(författare)
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Pharmacoinformatic approach to identify potential phytochemicals against SARS-CoV-2 spike receptor-binding domain in native and variants of concern
- 2022
-
Ingår i: Molecular diversity. - : Springer Nature. - 1381-1991 .- 1573-501X.
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) pathogenesis is initiated by the binding of SARS-CoV-2 spike (S) protein with the angiotensin-converting enzyme 2 receptor (ACE2R) on the host cell surface. The receptor-binding domain (RBD) of the S protein mediates the binding and is more prone to mutations resulting in the generation of different variants. Recently, molecules with the potential to inhibit the interaction of S protein with ACE2R have been of interest due to their therapeutic value. In this context, the present work was performed to identify potential RBD binders from the Indian medicinal plant's phytochemical database through virtual screening, molecular docking, and molecular dynamic simulation. Briefly, 1578 compounds filtered from 9596 phytochemicals were chosen for screening against the RBD of the native SARS-CoV-2 S protein. Based on the binding energy, the top 30 compounds were selected and re-docked individually against the native and five variants of concern (VOCs: alpha, beta, gamma, delta, and omicron) of SARS-CoV-2. Four phytochemicals, namely withanolide F, serotobenine, orobanchol, and gibberellin A51, were found to be potential RBD binders in native and all SARS-CoV-2 VOCs. Among the four, withanolide F exhibited lower binding energy (− 10.84 to − 8.56 kcal/mol) and better ligand efficiency (− 0.3 to − 0.25) against all forms of RBD and hence was subjected to a 100 ns MD simulation which confirmed its stringent binding to the RBDs in native and VOCs. The study prioritizes withanolide F as a prospective COVID-19 (Coronavirus disease) therapeutic agent based on the observations. It warrants deeper investigations into the four promising leads for understanding their precise therapeutic value. Graphical abstract: [Figure not available: see fulltext.].
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| 12. |
- Dhumal, Tushar Tukaram, et al.
(författare)
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Molecular explorations of the Leishmania donovani 6-phosphogluconolactonase enzyme, a key player in the pentose phosphate pathway
- 2022
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Ingår i: Biochimie. - : Elsevier BV. - 0300-9084 .- 1638-6183. ; 202, s. 212-225
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Tidskriftsartikel (refereegranskat)abstract
- The enzymes of the pentose phosphate pathway are vital to survival in kinetoplastids. The second step of the pentose phosphate pathway involves hydrolytic cleavage of 6-phosphogluconolactone to 6- phosphogluconic acid by 6-phosphogluconolactonase (6PGL). In the present study, Leishmania dono-vani 6PGL (Ld6PGL) was cloned and overexpressed in bacterial expression system. Comparative sequence analysis revealed the conserved sequence motifs, functionally and structurally important residues in 6PGL family. In silico amino acid substitution study and interacting partners of 6PGL were predicted. The Ld6PGL enzyme was found to be active in the assay and in the parasites. Specificity was confirmed by Western blot analysis. The similar to 30 kDa protein was found to be a dimer in MALDI, glutaraldehyde cross-linking and size exclusion chromatography studies. Kinetic analysis and structural stability studies of Ld6PGL were performed with denaturants and at varied temperature. Computational 3D Structural modelling of Ld6PGL elucidates that it has a similar a/b hydrolase fold structural topology as in other members of 6PGL family. The three loops are found in extended form when the structure is compared with the human 6PGL (Hs6PGL). Further, enzyme substrate binding mode and its mechanism were investigated using the molecular docking and molecular simulation studies. Interesting dynamics action of substrate 6-phosphogluconolactone was observed into active site during MD simulation. Interesting differences were observed between host and parasite enzyme which pointed towards its potential to be explored as an antileishmanial drug target. This study forms the basis for further analysis of the role of Ld6PGL in combating oxidative stress in Leishmania.
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| 13. |
- Gahlawat, Anuj, et al.
(författare)
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Structure-Based Virtual Screening to Discover Potential Lead Molecules for the SARS-CoV-2 Main Protease.
- 2020
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 60:12, s. 5781-5793
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 disease is caused by a new strain of the coronavirus family (SARS-CoV-2), and it has affected at present millions of people all over the world. The indispensable role of the main protease (Mpro) in viral replication and gene expression makes this enzyme an attractive drug target. Therefore, inhibition of SARS-CoV-2 Mpro as a proposition to halt virus ingression is being pursued by scientists globally. Here we carried out a study with two objectives: the first being to perform comparative protein sequence and 3D structural analysis to understand the effect of 12 point mutations on the active site. Among these, two mutations, viz., Ser46 and Phe134, were found to cause a significant change at the active sites of SARS-CoV-2. The Ser46 mutation present at the entrance of the S5 subpocket of SARS-CoV-2 increases the contribution of other two hydrophilic residues, while the Phe134 mutation, present in the catalytic cysteine loop, can cause an increase in catalytic efficiency of Mpro by facilitating fast proton transfer from the Cys145 to His41 residue. It was observed that active site remained conserved among Mpro of both SARS-CoVs, except at the entrance of the S5 subpocket, suggesting sustenance of substrate specificity. The second objective was to screen the inhibitory effects of three different data sets (natural products, coronaviruses main protease inhibitors, and FDA-approved drugs) using a structure-based virtual screening approach. A total of 73 hits had a combo score >2.0. Eight different structural scaffold classes were identified, such as one/two tetrahydropyran ring(s), dipeptide/tripeptide/oligopeptide, large (approximately 20 atoms) cyclic peptide, and miscellaneous. The screened hits showed key interactions with subpockets of the active site. Further, molecular dynamics studies of selected screened compounds confirmed their perfect fitting into the subpockets of the active site. This study suggests promising structures that can fit into the SARS-CoV-2 Mpro active site and also offers direction for further lead optimization and rational drug design.
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| 14. |
- Kumar, Rajender, et al.
(författare)
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Biochemical characterization and molecular insights into substrate recognition of pectin methylesterase from Phytophthora infestans
- 2022
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Ingår i: Computational and Structural Biotechnology Journal. - : Elsevier BV. - 2001-0370. ; 20, s. 6023-6032
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Tidskriftsartikel (refereegranskat)abstract
- Pectin methylesterases (PMEs) are a class of carbohydrate-active enzymes that act on the O6-methyl ester groups of the homogalacturonan component of pectins, resulting in de-esterification of the sub-strate polymers and formation of pectate and methanol. PMEs occur in higher plants and microorgan-isms, including fungi, oomycetes, bacteria, and archaea. Microbial PMEs play a crucial role in pathogens' invasion of plant tissues. Here, we have determined the structural and functional properties of Pi-PME, a PME from the oomycete plant pathogen Phytophthora infestans. This enzyme exhibits maxi-mum activity at alkaline pH (8.5) and is active over a wide temperature range (25-50 degrees C). In silico deter-mination of the structure of Pi-PME reveals that the protein consists essentially of three parallel 8-sheets interconnected by loops that adopt an overall 8-helix organization. The loop regions in the vicinity of the active site are extended compared to plant and fungal PMEs, but they are shorter than the corresponding bacterial and insect regions. Molecular dynamic simulations revealed that Pi-PME interacts most strongly with partially de-methylated homogalacturonans, suggesting that it preferentially uses this type of sub-strates. The results are compared and discussed with other known PMEs from different organisms, high-lighting the specific features of Pi-PME.
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| 15. |
- Kumar, Rajender, et al.
(författare)
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Sequence, structure and functionality of pectin methylesterases and their use in sustainable carbohydrate bioproducts : A review
- 2023
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 244
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Tidskriftsartikel (refereegranskat)abstract
- Pectin methylesterases (PMEs) are enzymes that play a critical role in modifying pectins, a class of complex polysaccharides in plant cell walls. These enzymes catalyze the removal of methyl ester groups from pectins, resulting in a change in the degree of esterification and consequently, the physicochemical properties of the polymers. PMEs are found in various plant tissues and organs, and their activity is tightly regulated in response to developmental and environmental factors. In addition to the biochemical modification of pectins, PMEs have been implicated in various biological processes, including fruit ripening, defense against pathogens, and cell wall remodelling. This review presents updated information on PMEs, including their sources, sequences and structural diversity, biochemical properties and function in plant development. The article also explores the mechanism of PME action and the factors influencing enzyme activity. In addition, the review highlights the potential applications of PMEs in various industrial sectors related to biomass exploitation, food, and textile industries, with a focus on development of bioproducts based on eco-friendly and efficient industrial processes.
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| 16. |
- Kumar, Rajender, et al.
(författare)
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Structural–functional analysis of drug target aspartate semialdehyde dehydrogenase
- 2024
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 29:3
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Forskningsöversikt (refereegranskat)abstract
- Aspartate β-semialdehyde dehydrogenase (ASADH) is a key enzyme in the biosynthesis of essential amino acids in microorganisms and some plants. Inhibition of ASADHs can be a potential drug target for developing novel antimicrobial and herbicidal compounds. This review covers up-to-date information about sequence diversity, ligand/inhibitor-bound 3D structures, potential inhibitors, and key pharmacophoric features of ASADH useful in designing novel and target-specific inhibitors of ASADH. Most reported ASADH inhibitors have two highly electronegative functional groups that interact with two key arginyl residues present in the active site of ASADHs. The structural information, active site binding modes, and key interactions between the enzyme and inhibitors serve as the basis for designing new and potent inhibitors against the ASADH family.
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| 17. |
- Meghwanshi, Gautam Kumar, et al.
(författare)
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Archaeal lipolytic enzymes : Current developments and further prospects
- 2022
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Ingår i: Biotechnology Advances. - : Elsevier BV. - 0734-9750 .- 1873-1899. ; 61
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Forskningsöversikt (refereegranskat)abstract
- Lipolytic enzymes include triacylglycerol lipases (EC 3.1.1.3) and esterases (EC 3.1.1.1) that catalyze the cleavage and formation of ester bonds. They are potential industrial biocatalysts because of their broad range of activities on natural and synthetic substrates, high stability in organic solvents, thermal stability, stability in highly acidic and alkaline pH conditions and enantio-, regio-and chemo-selectivity. They also have varied ap-plications in different sectors, among which industrial biotechnology, the production of cleaning agents, and pharmaceuticals are the most important ones. Identifying extremophilic lipolytic enzymes is of paramount in-terest and is a growing field in academic and industrial research. This review is focused on the current knowledge and future avenues of investigation on lipolytic enzymes sourced from the underexploited archaeal domain. Archaea is a potential source for novel extremophilic enzymes, which have high demand in the industries. The archaeal lipases and esterases are clustered into different families based on their similarity/dissimilarity at the genetic level and protein structures. The updated information on characterized and putative lipase sequences has also been presented in this paper. Common structural scaffolds of archaeal lipases have been deduced and dis-cussed in this review. However, huge diversity at the level of their genetic sequences has yet to be correlated with the structure-function relationship. Based on their biochemical properties, possible applications and future prospective of archaeal lipolytic enzymes have also been proposed.
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| 18. |
- Ponne, Saravanaraman, et al.
(författare)
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Reverse engineering protection : A comprehensive survey of reverse vaccinology-based vaccines targeting viral pathogens
- 2024
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 42:10, s. 2503-2518
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Forskningsöversikt (refereegranskat)abstract
- Vaccines have significantly reduced the impact of numerous deadly viral infections. However, there is an increasing need to expedite vaccine development in light of the recurrent pandemics and epidemics. Also, identifying vaccines against certain viruses is challenging due to various factors, notably the inability to culture certain viruses in cell cultures and the wide-ranging diversity of MHC profiles in humans. Fortunately, reverse vaccinology (RV) efficiently overcomes these limitations and has simplified the identification of epitopes from antigenic proteins across the entire proteome, streamlining the vaccine development process. Furthermore, it enables the creation of multiepitope vaccines that can effectively account for the variations in MHC profiles within the human population. The RV approach offers numerous advantages in developing precise and effective vaccines against viral pathogens, including extensive proteome coverage, accurate epitope identification, crossprotection capabilities, and MHC compatibility. With the introduction of RV, there is a growing emphasis among researchers on creating multiepitope-based vaccines aiming to stimulate the host's immune responses against multiple serotypes, as opposed to single-component monovalent alternatives. Regardless of how promising the RV-based vaccine candidates may appear, they must undergo experimental validation to probe their protection efficacy for real-world applications. The time, effort, and resources allocated to the laborious epitope identification process can now be redirected toward validating vaccine candidates identified through the RV approach. However, to overcome failures in the RV-based approach, efforts must be made to incorporate immunological principles and consider targeting the epitope regions involved in disease pathogenesis, immune responses, and neutralizing antibody maturation. Integrating multi-omics and incorporating artificial intelligence and machine learning-based tools and techniques in RV would increase the chances of developing an effective vaccine. This review thoroughly explains the RV approach, ideal RV-based vaccine construct components, RV-based vaccines designed to combat viral pathogens, its challenges, and future perspectives.
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| 19. |
- Singh, Rajesh, et al.
(författare)
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Removal of sulphate, COD and Cr(VI) in simulated and real wastewater by sulphate reducing bacteria enrichment in small bioreactor and FTIR study
- 2011
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 102:2, s. 677-682
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Tidskriftsartikel (refereegranskat)abstract
- The present study was conducted to investigate the chromium(VI), COD and sulphate removal efficiency from aqueous solution and treatment of real effluent (CETP) in a small scale bioreactor using sulphate reducing bacteria consortium. Effect of different hydraulic retention times (HRTs), initial metal concentrations, various carbon sources and temperatures were studied on removal of chromium(VI), COD and sulphate. Maximum chromium(VI) and sulphate removal was found to be 96.0% and 82.0%, respectively, at initial concentration of 50 mg l(-1) using lactate as carbon source. However, highest COD removal was 36.2% in medium containing fructose as the carbon source and electron donor. NADH dependent chromate reductase activity was not observed which indicated the anaerobic consortium. Initially consortium medium with a strong negative oxidation reduction potential indicated the reducing activity. The FTIR spectrum of the sulphate reducing bacteria consortium clearly shows the existence of the sulphate ions and signifies that sulfate reducing bacteria have used sulfate during the growth phase.
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| 20. |
- Srivastava, A., et al.
(författare)
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Gamma (γ)-radiation stress response of the cyanobacterium Anabaena sp. PCC7120 : Regulatory role of LexA and photophysiological changes
- 2023
-
Ingår i: Plant Science. - : Elsevier BV. - 0168-9452 .- 1873-2259. ; 326, s. 111529-
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Tidskriftsartikel (refereegranskat)abstract
- High radioresistance of the cyanobacterium, Anabaena sp. PCC7120 has been attributed to efficient DNA repair, protein recycling, and oxidative stress management. However, the regulatory network involved in these batteries of responses remains unexplored. In the present study, the role of a global regulator, LexA in modulating gamma (γ)-radiation stress response of Anabaena was investigated. Comparison of the cytosolic proteome profiles upon γ-radiation in recombinant Anabaena strains, AnpAM (vector-control) and AnlexA+ (LexA-overexpressing), revealed 41 differentially accumulated proteins, corresponding to 29 distinct proteins. LexA was found to be involved in the regulation of 27 of the corresponding genes based on the presence of AnLexA-Box, EMSA, and/or qRT-PCR studies. The majority of the regulated genes were found to be involved in C-assimilation either through photosynthesis or C-catabolism and oxidative stress alleviation. Photosynthesis, measured in terms of PSII photophysiological parameters and thylakoid membrane proteome was found to be affected by γ-radiation in both AnpAM and AnlexA+ cells, with LexA affecting them even under control growth conditions. Thus, LexA functioned as one of the transcriptional regulators involved in modulating γ-radiation stress response in Anabaena. This study could pave the way for a deeper understanding of the regulation of γ-radiation-responsive genes in cyanobacteria at large.
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| 21. |
- Verma, Swati, et al.
(författare)
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Current perspectives for microbial lipases from extremophiles and metagenomics
- 2021
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Ingår i: Biochimie. - : Elsevier. - 0300-9084 .- 1638-6183. ; 182, s. 23-36
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Forskningsöversikt (refereegranskat)abstract
- Microbial lipases are most broadly used biocatalysts for environmental and industrial applications. Lipases catalyze the hydrolysis and synthesis of long acyl chain esters and have a characteristic folding pattern of α/β hydrolase with highly conserved catalytic triad (Serine, Aspartic/Glutamic acid and Histidine). Mesophilic lipases (optimal activity in neutral pH range, mesophilic temperature range, atmospheric pressure, normal salinity, non-radio-resistant, and instability in organic solvents) have been in use for many industrial biotransformation reactions. However, lipases from extremophiles can be used to design biotransformation reactions with higher yields, less byproducts or useful side products and have been predicted to catalyze those reactions also, which otherwise are not possible with the mesophilic lipases. The extremophile lipase perform activity at extremes of temperature, pH, salinity, and pressure which can be screened from metagenome and de novo lipase design using computational approaches. Despite structural similarity, they exhibit great diversity at the sequence level. This diversity is broader when lipases from the bacterial, archaeal, plant, and animal domains/kingdoms are compared. Furthermore, a great diversity of novel lipases exists and can be discovered from the analysis of the dark matter - the unexplored nucleotide/metagenomic databases. This review is an update on extremophilic microbial lipases, their diversity, structure, and classification. An overview on novel lipases which have been detected through analysis of the genomic dark matter (metagenome) has also been presented.
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| 22. |
- Verma, Swati, et al.
(författare)
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Identification of new members of alkaliphilic lipases in archaea and metagenome database using reconstruction of ancestral sequences
- 2019
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Ingår i: 3 Biotech. - : Springer Berlin/Heidelberg. - 2190-5738 .- 2190-572X. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- The application of bioinformatics in lipase research has the potential to discover robust members from different genomic/metagenomic databses. In this study, we explored the diversity and distribution of alkaliphilic lipases in archaea domain and metagenome data sets through phylogenetic survey. Reconstructed ancestral sequence of alkaphilic lipase was used to search the homologous alkaliphilic lipases among the archaea and metagenome public databases. Our investigation revealed a total 21 unique sequences of new alkaliphilic lipases in the archaeal and environmental metagenomic protein databases that shared significant sequence similarity to the bacterial alkaliphilic lipases. Most of the identified new members of alkaliphilic lipases belong to class Haloarchaea. The searched list of homologs also comprised of one characterized lipase from alkalohyperthermophilic Archaeoglobus fulgidus. All the newly identified alkaliphilic lipase members showed conserved pentapeptide [X-His-Ser-X-Gly] motif, a key feature of lipase family. Furthermore, detailed analysis of all these new sequences showed homology either with thermostable or alkalophilic lipases. The reconstructed ancestral sequence-based searches increased the sensitivity and efficacies to detect remotely homologous sequences. We hypothesize that this study can enrich our current knowledge on lipases in designing more potential thermo-alkaliphilic lipases for industrial applications.
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| 23. |
- Alam, Athar, et al.
(författare)
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Dissociation between the critical role of ClpB of Francisella tularensis for the heat shock response and the DnaK interaction and its important role for efficient type VI secretion and bacterial virulence
- 2020
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Ingår i: PLoS Pathogens. - : Public Library of Science. - 1553-7366 .- 1553-7374. ; 16:4, s. 1-27
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Tidskriftsartikel (refereegranskat)abstract
- Author summary Type VI secretion systems (T6SSs) are essential virulence determinants of many Gram-negative pathogens, including Francisella tularensis. This highly virulent bacterium encodes an atypical T6SS lacking ClpV, the ATPase crucial for prototypic T6SS sheath disassembly. It, however, possesses ClpB, a protein critical for heat shock survival via its interaction with DnaK. Since ClpB possesses ATPase activity, it has been hypothesized to provide a compensatory function for the absence of ClpV, a hypothesis supported by the recent findings from us and others. Here, we investigated how F. tularensis ClpB controls T6S. In silico modelling of the ClpB-DnaK complex identified key interactions that were experimentally verified. For example, mutating one of the DnaK-interacting residues rendered the bacterium exquisitely susceptible to heat shock, but had no effect on T6S and virulence. In contrast, removing the N-terminal of ClpB only had a slight effect on the heat shock response, but strongly compromised both T6S and virulence. Intriguingly, the Escherichia coli ClpB could fully complement the function of F. tularensis ClpB. The data demonstrate that the two critical roles of ClpB, mediating heat shock survival and effective T6S, are dissociated and that the N-terminal is crucial for T6S and virulence. Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for its virulence. The chaperone ClpB, a member of the Hsp100/Clp family, is involved in Francisella T6SS disassembly and type VI secretion (T6S) is impaired in its absence. We asked if the role of ClpB for T6S was related to its prototypical role for the disaggregation activity. The latter is dependent on its interaction with the DnaK/Hsp70 chaperone system. Key residues of the ClpB-DnaK interaction were identified by molecular dynamic simulation and verified by targeted mutagenesis. Using such targeted mutants, it was found that the F. novicida ClpB-DnaK interaction was dispensable for T6S, intracellular replication, and virulence in a mouse model, although essential for handling of heat shock. Moreover, by mutagenesis of key amino acids of the Walker A, Walker B, and Arginine finger motifs of each of the two Nucleotide-Binding Domains, their critical roles for heat shock, T6S, intracellular replication, and virulence were identified. In contrast, the N-terminus was dispensable for heat shock, but required for T6S, intracellular replication, and virulence. Complementation of the Delta clpB mutant with a chimeric F. novicida ClpB expressing the N-terminal of Escherichia coli, led to reconstitution of the wild-type phenotype. Collectively, the data demonstrate that the ClpB-DnaK interaction does not contribute to T6S, whereas the N-terminal and NBD domains displayed critical roles for T6S and virulence.
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| 24. |
- Alam, Athar, et al.
(författare)
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The Role of ClpB in Bacterial Stress Responses and Virulence
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media S.A.. - 2296-889X. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Bacterial survival within a mammalian host is contingent upon sensing environmental perturbations and initiating an appropriate counter-response. To achieve this, sophisticated molecular machineries are used, where bacterial chaperone systems play key roles. The chaperones are a prerequisite for bacterial survival during normal physiological conditions as well as under stressful situations, e.g., infection or inflammation. Specific stress factors include, but are not limited to, high temperature, osmolarity, pH, reactive oxidative species, or bactericidal molecules. ClpB, a member of class 1 AAA+ proteins, is a key chaperone that via its disaggregase activity plays a crucial role for bacterial survival under various forms of stress, in particular heat shock. Recently, it has been reported that ClpB also regulates secretion of bacterial effector molecules related to type VI secretion systems. In this review, the roles of ClpB in stress responses and the mechanisms by which it promotes survival of pathogenic bacteria are discussed.
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| 25. |
- de Oliveira, Andressa Souza, et al.
(författare)
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Antifungal activity of sustainable histone deacetylase inhibitors against planktonic cells and biofilms of Candida spp. and Cryptococcusneoformans
- 2023
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Ingår i: Medical Mycology. - : Oxford University Press (OUP). - 1369-3786 .- 1460-2709. ; 61:8
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Tidskriftsartikel (refereegranskat)abstract
- The limited therapeutic options for fungal infections and the increased incidence of fungal strains resistant to antifungal drugs, especially Candida spp., require the development of new antifungal drugs and strategies. Histone deacetylase inhibitors (HDACi), like vorinostat, have been studied in cancer treatment and have antifungal effects, acting alone or synergistically with classical antifungals. Here we investigated the antifungal activity of two novel sustainable HDACi (LDT compounds) based on vorinostat structure. Molecular docking simulation studies reveal that LDT compounds can bind to Class-I HDACs of Candida albicans, C. tropicalis, and Cryptococcus neoformans, which showed similar binding mode to vorinostat. LDT compounds showed moderate activity when tested alone against fungi but act synergistically with antifungal azoles against Candida spp. They reduced biofilm formation by more than 50% in C. albicans (4 µg/mL), with the main action in fungal filamentation. Cytotoxicity of the LDT compounds against RAW264.7 cells was evaluated and LDT536 demonstrated cytotoxicity only at the concentration of 200 µmol/L, while LDT537 showed IC50 values of 29.12 µmol/L. Our data indicated that these sustainable and inexpensive HDACi have potential antifungal and antibiofilm activities, with better results than vorinostat, although further studies are necessary to better understand the mechanism against fungal cells.
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| 26. |
- Harshita, S., et al.
(författare)
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Genetic Privacy Shields: A DNA Steganography Approach for Multi-Level Text Encryption : iling the Future of Genetic Data Protection
- 2023
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Ingår i: 2023 1st International Conference on Advances in Electrical, Electronics and Computational Intelligence, ICAEECI 2023. - : Institute of Electrical and Electronics Engineers (IEEE). - 9798350342796
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Konferensbidrag (refereegranskat)abstract
- In the current era genetic sequencing has emerged as an indispensable methodology for examining diverse DNA profiles across domains encompassing healthcare, agriculture, and forensic science. To enhance precision, a range of techniques, including high-throughput shotgun sequencing, have evolved over time. Recent strides in next-generation sequencing methodologies have facilitated the embedding of data within DNA using synthesized oligonucleotides. Notably, significant efforts have been dedicated to embedding extensive volumes of information within living organisms to safeguard intellectual property. When it comes to DNA steganography, traditional detection methods, exemplified by frequency analysis-based approaches, often overlook crucial signals and are susceptible to newly emerging steganography techniques. This study undertakes a comprehensive analysis of inherent allocations, distribution variance computation, and the classification of sequences as coding or non-coding. Our research endeavors to devise an advanced security strategy employing DNA steganography. Central to our proposition is the utilization of DNA steganography to forge a robust security framework. In this study, we introduce the DNA-Genetic Encryption (D-GET) mechanism to augment security. The D-GET technique involves the binarization of digital data followed by its conversion into DNA sequences. Subsequently, a sequence of operations, including reshaping, encryption, crossover, and mutation, is performed iteratively to heighten the robustness and unpredictability of the technique. The core processes of D-GET are iterated at least three times. Encrypted data is transmitted in either text or image file formats. Upon reception, the D-GET approach is employed to decode and restore the acquired data to its original form. A distinguishing aspect of our approach is the transformation of textual content into visual representations and vice versa, augmenting security measures. Multiple key sequences are leveraged to amplify the degree of dispersion and ambiguity, rendering the final cipher data highly intricate to decipher. Empirical observations highlight that our proposed methodology affords multi-layered security attributes, fortified by multi-stage and genetic operations, rendering it resilient against diverse threats and affording an elevated level of safeguarding. Notably, the methodology's efficacy derives from the pronounced divergence between the transformed information and the confidential content, thereby reinforcing the integrity of the encryption framework.
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| 27. |
- Kumar, Rajender, et al.
(författare)
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Exploring the Diversity Within the Genus Francisella – An Integrated Pan-Genome and Genome-Mining Approach
- 2020
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Pan-genome analysis is a powerful method to explore genomic heterogeneity and diversity of bacterial species. Here we present a pan-genome analysis of the genus Francisella, comprising a dataset of 63 genomes and encompassing clinical as well as environmental isolates from distinct geographic locations. To determine the evolutionary relationship within the genus, we performed phylogenetic whole-genome studies utilizing the average nucleotide identity, average amino acid identity, core genes and non-recombinant loci markers. Based on the analyses, the phylogenetic trees obtained identified two distinct clades, A and B and a diverse cluster designated C. The sizes of the pan-, core-, cloud-, and shell-genomes of Francisella were estimated and compared to those of two other facultative intracellular pathogens, Legionella and Piscirickettsia. Francisella had the smallest core-genome, 692 genes, compared to 886 and 1,732 genes for Legionella and Piscirickettsia respectively, while the pan-genome of Legionella was more than twice the size of that of the other two genera. Also, the composition of the Francisella Type VI secretion system (T6SS) was analyzed. Distinct differences in the gene content of the T6SS were identified. In silico approaches performed to identify putative substrates of these systems revealed potential effectors targeting the cell wall, inner membrane, cellular nucleic acids as well as proteins, thus constituting attractive targets for site-directed mutagenesis. The comparative analysis performed here provides a comprehensive basis for the assessment of the phylogenomic relationship of members of the genus Francisella and for the identification of putative T6SS virulence traits.
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| 28. |
- Kumar, Rajender, et al.
(författare)
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Improved Binding Affinity of Omicron's Spike Protein for the Human Angiotensin-Converting Enzyme 2 Receptor Is the Key behind Its Increased Virulence
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:6
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Tidskriftsartikel (refereegranskat)abstract
- The new variant of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), Omicron, has been quickly spreading in many countries worldwide. Compared to the original virus, Omicron is characterized by several mutations in its genomic region, including the spike protein's receptor-binding domain (RBD). We have computationally investigated the interaction between the RBD of both the wild type and Omicron variant of SARS-CoV-2 with the human angiotensin-converting enzyme 2 (hACE2) receptor using molecular dynamics and molecular mechanics-generalized Born surface area (MM-GBSA)-based binding free energy calculations. The mode of the interaction between Omicron's RBD with the hACE2 receptor is similar to the original SARS-CoV-2 RBD except for a few key differences. The binding free energy difference shows that the spike protein of Omicron has an increased affinity for the hACE2 receptor. The mutated residues in the RBD showed strong interactions with a few amino acid residues of hACE2. More specifically, strong electrostatic interactions (salt bridges) and hydrogen bonding were observed between R493 and R498 residues of the Omicron RBD with D30/E35 and D38 residues of the hACE2, respectively. Other mutated amino acids in the Omicron RBD, e.g., S496 and H505, also exhibited hydrogen bonding with the hACE2 receptor. A pi-stacking interaction was also observed between tyrosine residues (RBD-Tyr501: hACE2-Tyr41) in the complex, which contributes majorly to the binding free energies and suggests that this is one of the key interactions stabilizing the formation of the complex. The resulting structural insights into the RBD:hACE2 complex, the binding mode information within it, and residue-wise contributions to the free energy provide insight into the increased transmissibility of Omicron and pave the way to design and optimize novel antiviral agents.
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| 29. |
- Kumar, Rajender
(författare)
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Structural dynamics and mechanistic action guided engineering of lipolytic enzymes
- 2023
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Ingår i: Journal of Cellular Biochemistry. - : Wiley. - 0730-2312 .- 1097-4644. ; 124:6, s. 877-888
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Tidskriftsartikel (refereegranskat)abstract
- Lipases have been established as important biocatalysts in several industrial applications, owing to their diverse substrate specificity. The availability of data on three-dimensional crystal structures for various lipases offers an opportunity for modulating their structural and functional aspects to design and engineer better versions of lipases. With the aim of investigating the structural components governing the extremophilic behavior of lipases, structural analysis of microbial lipases was performed using advanced bioinformatics and molecular dynamics simulation approaches. In sequences and functionally distinct alkaliphilic and thermophilic lipases were investigated for their functional properties to understand the distinguishing features of their structures. The alkaliphilic lipase from Bacillus subtilis (LipA) showed conformational changes in the loop region Ala132–Met137, subsequently, the active site residue His156 shows two conformations, toward the active site nucleophilic residues Ser77 and away from the Ser77. Interestingly, the active site of LipA is more solvent-exposed and can be correlated with the adoption of an open conformation which might extend and expose the active site region to solvents during the catalysis process. Furthermore, the MD simulation of thermophilic lipase from marine Streptomyces (MAS1) revealed the role of N- and C-terminal regions with disulfide bridges and identified a metal ion binding site that facilitates the enzyme stability. The novel thermo-alkaliphilic lipase can be designed to integrate the stability features of MAS1 into the alkaliphilic LipA. These structural-level intrinsic characteristics can be used for lipase engineering to amend the lipase activity and stability as per the requirements of the industrial processes.
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| 30. |
- Kumar, Vikas, et al.
(författare)
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Computational insights into allosteric inhibition of focal adhesion kinase: A combined pharmacophore modeling and molecular dynamics approach
- 2024
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Ingår i: JOURNAL OF MOLECULAR GRAPHICS & MODELLING. - 1093-3263 .- 1873-4243. ; 130
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Tidskriftsartikel (refereegranskat)abstract
- Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that modulates integrin and growth factor signaling pathways and is implicated in cancer cell migration, proliferation, and survival. Over the past decade various, FAK kinase, FERM, and FAT domain inhibitors have been reported and a few kinase domain inhibitors are under clinical consideration. However, few of them were identified as multikinase inhibitors. In kinase drug design selectivity is always a point of concern, to improve selectivity allosteric inhibitor development is the best choice. The current research utilized a pharmacophore modeling (PM) approach to identify novel allosteric inhibitors of FAK. The all-available allosteric inhibitor bound 3D structures with PDB ids 4EBV, 4EBW, and 4I4F were utilized for the pharmacophore modeling. The validated PM models were utilized to map a database of 770,550 compounds prepared from ZINC, EXIMED, SPECS, ASINEX, and InterBioScreen, aiming to identify potential allosteric inhibitors. The obtained compounds from screening step were forwarded to molecular docking (MD) for the prediction of binding orientation inside the allosteric site and the results were evaluated with the known FAK allosteric inhibitor (REF). Finally, 14 FAK-inhibitor complexes were selected from the docking study and were studied under molecular dynamics simulations (MDS) for 500 ns. The complexes were ranked according to binding free energy (BFE) and those demonstrated higher affinity for allosteric site of FAK than REF inhibitors were selected. The selected complexes were further analyzed for intermolecular interactions and finally, three potential allosteric inhibitor candidates for the inhibition of FAK protein were identified. We believe that identified scaffolds may help in drug development against FAK as an anticancer agent.
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| 31. |
- Sadik, May, 1970, et al.
(författare)
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Artificial intelligence could alert for focal skeleton/bone marrow uptake in Hodgkin’s lymphoma patients staged with FDG-PET/CT
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- To develop an artificial intelligence (AI)-based method for the detection of focal skeleton/bone marrow uptake (BMU) in patients with Hodgkin’s lymphoma (HL) undergoing staging with FDG-PET/CT. The results of the AI in a separate test group were compared to the interpretations of independent physicians. The skeleton and bone marrow were segmented using a convolutional neural network. The training of AI was based on 153 un-treated patients. Bone uptake significantly higher than the mean BMU was marked as abnormal, and an index, based on the total squared abnormal uptake, was computed to identify the focal uptake. Patients with an index above a predefined threshold were interpreted as having focal uptake. As the test group, 48 un-treated patients who had undergone a staging FDG-PET/CT between 2017–2018 with biopsy-proven HL were retrospectively included. Ten physicians classified the 48 cases regarding focal skeleton/BMU. The majority of the physicians agreed with the AI in 39/48 cases (81%) regarding focal skeleton/bone marrow involvement. Inter-observer agreement between the physicians was moderate, Kappa 0.51 (range 0.25–0.80). An AI-based method can be developed to highlight suspicious focal skeleton/BMU in HL patients staged with FDG-PET/CT. Inter-observer agreement regarding focal BMU is moderate among nuclear medicine physicians.
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| 32. |
- Sadik, May, 1970, et al.
(författare)
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Metabolic tumour volume in Hodgkin lymphoma - A comparison between manual and AI-based analysis
- 2024
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961 .- 1475-097X. ; 44:3, s. 220-227
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To compare total metabolic tumour volume (tMTV), calculated using two artificial intelligence (AI)-based tools, with manual segmentation by specialists as the reference. Methods: Forty-eight consecutive Hodgkin lymphoma (HL) patients staged with [18F] fluorodeoxyglucose positron emission tomography/computed tomography were included. The median age was 35 years (range: 7–75), 46% female. The tMTV was automatically measured using the AI-based tools positron emission tomography assisted reporting system (PARS) (from Siemens) and RECOMIA (recomia.org) without any manual adjustments. A group of eight nuclear medicine specialists manually segmented lesions for tMTV calculations; each patient was independently segmented by two specialists. Results: The median of the manual tMTV was 146 cm3 (interquartile range [IQR]: 79–568 cm3) and the median difference between two tMTV values segmented by different specialists for the same patient was 26 cm3 (IQR: 10–86 cm3). In 22 of the 48 patients, the manual tMTV value was closer to the RECOMIA tMTV value than to the manual tMTV value segmented by the second specialist. In 11 of the remaining 26 patients, the difference between the RECOMIA tMTV and the manual tMTV was small (<26 cm3, which was the median difference between two manual tMTV values from the same patient). The corresponding numbers for PARS were 18 and 10 patients, respectively. Conclusion: The results of this study indicate that RECOMIA and Siemens PARS AI tools could be used without any major manual adjustments in 69% (33/48) and 58% (28/48) of HL patients, respectively. This demonstrates the feasibility of using AI tools to support physicians measuring tMTV for assessment of prognosis in clinical practice.
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