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INTRODUCTION: The Cluster bean is an economically significant annual legume, widely known as guar. Plant productivity is frequently constrained by drought conditions. OBJECTIVE: In this work, we have identified the untargeted drought stress-responsive metabolites in mature leaves of cluster beans under drought and control condition. METHODS: To analyse the untargeted metabolites, gas chromatography-mass spectrometry (GC-MS) technique was used. Supervised partial least-squares discriminate analysis and heat map were used to identify the most significant metabolites for drought tolerance. RESULTS: The mature leaves of drought-treated C. tetragonoloba cv. 'HG-365' which is a drought-tolerant cultivar, showed various types of amino acids, fatty acids, sugar alcohols and sugars as the major classes of metabolites recognized by GC-MS metabolome analysis. Metabolite profiling of guar leaves showed 23 altered metabolites. Eight metabolites (proline, valine, D-pinitol, palmitic acid, dodecanoic acid, threonine, glucose, and glycerol monostearate) with VIP score greater than one were considered as biomarkers and three metabolite biomarkers (D-pinitol, valine, and glycerol monostearate) were found for the first time in guar under drought stress. In this work, four amino acids (alanine, valine, serine and aspartic acid) were also studied, which played a significant role in drought-tolerant pathway in guar. CONCLUSION: This study provides information on the first-ever GC-MS metabolic profiling of guar. This work gives in-depth details on guar's untargeted drought-responsive metabolites and biomarkers, which can plausibly be used for further identification of biochemical pathways, enzymes, and the location of various genes under drought stress.
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Biomarcadores , Sequías , Cromatografía de Gases y Espectrometría de Masas , Metabolómica , Hojas de la Planta , Estrés Fisiológico , Cromatografía de Gases y Espectrometría de Masas/métodos , Metabolómica/métodos , Biomarcadores/metabolismo , Biomarcadores/análisis , Hojas de la Planta/metabolismo , Estrés Fisiológico/fisiología , Metaboloma/fisiología , Aminoácidos/metabolismo , Aminoácidos/análisis , Fabaceae/metabolismoRESUMEN
Increasing incidences of fungal infections and prevailing antifungal resistance in healthcare settings has given rise to an antifungal crisis on a global scale. The members of the genus Candida, owing to their ability to acquire sessile growth, are primarily associated with superficial to invasive fungal infections, including the implant-associated infections. The present study introduces a novel approach to combat the sessile/biofilm growth of Candida by fabricating nanofibers using a nanoencapsulation approach. This technique involves the synthesis of tyrosol (TYS) functionalized chitosan gold nanocomposite, which is then encapsulated into PVA/AG polymeric matrix using electrospinning. The FESEM, FTIR analysis of prepared TYS-AuNP@PVA/AG NF suggested the successful encapsulation of TYS into the nanofibers. Further, the sustained and long-term stability of TYS in the medium was confirmed by drug release and storage stability studies. The prepared nanomats can absorb the fluid, as evidenced by the swelling index of the nanofibers. The growth and biofilm inhibition, as well as the disintegration studies against Candida, showed 60-70 % biofilm disintegration when 10 mg of TYS-AuNP@PVA/AG NF was used, hence confirming its biological effectiveness. Subsequently, the nanofibers considerably reduced the hydrophobicity index and ergosterol content of the treated cells. Considering the challenges associated with the inhibition/disruption of fungal biofilm, the fabricated nanofibers prove their effectiveness against Candida biofilm. Therefore, nanocomposite-loaded nanofibers have emerged as potential materials that can control fungal colonization and could also promote healing.
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Antifúngicos , Biopelículas , Candida , Oro , Goma Arábiga , Nanopartículas del Metal , Nanofibras , Alcohol Feniletílico , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Oro/química , Oro/farmacología , Nanofibras/química , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/química , Nanopartículas del Metal/química , Antifúngicos/farmacología , Candida/efectos de los fármacos , Goma Arábiga/química , Goma Arábiga/farmacología , Quitosano/química , Quitosano/farmacología , Nanocompuestos/química , Pruebas de Sensibilidad Microbiana , Alcohol Polivinílico/química , Liberación de Fármacos , Plata/farmacología , Plata/química , Ergosterol/química , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
In the present work, new chiral stationary phase high-performance liquid chromatography (CSP-HPLC) method was established and validated for the quantification of pomalidomide (PMD) enantiomers in human plasma. The chromatographic enantiomeric separation was achieved on a Daicel-CSP, Chiralpack IA 4.6 × 250 mm, 5 µm; because of its advantages of high degree of retention, high resolution capacity, better reproducibility, ability to produce lower back pressure and low degree of tailing. The mobile phase was maintained as methanol: glacial acetic acid (499.50 ml:50 µL). Ultraviolet wavelength for detection was 220 nm. PMD enantiomer-I and enantiomer-II were separated at 8.83 and 15.34 min, respectively. Limit of detection and limit of quantification for each enantiomer and the calibration curve of standard PMD was linear in range between 10-5,000 ng mL-1. The method was validated according to The International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH(Q2R1)) specific guidelines. We found no interference peak with PMD chromatogram obtained. This is a simple, reliable and specific method for detection and quantification of enantiomer of PMD in human plasma sample.
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Fusarium oxysporum f.sp. lycopersici is a phytopathogen which causes vascular wilt disease in tomato plants. The survival tactics of both pathogens and hosts depend on intricate interactions between host plants and pathogenic microbes. Iron-binding proteins (IBPs) and copper-binding proteins (CBPs) play a crucial role in these interactions by participating in enzyme reactions, virulence, metabolism, and transport processes. We employed high-throughput computational tools at the sequence and structural levels to investigate the IBPs and CBPs of F. oxysporum. A total of 124 IBPs and 37 CBPs were identified in the proteome of Fusarium. The ranking of amino acids based on their affinity for binding with iron is Glu > His> Asp > Asn > Cys, and for copper is His > Asp > Cys respectively. The functional annotation, determination of subcellular localization, and Gene Ontology analysis of these putative IBPs and CBPs have unveiled their potential involvement in a diverse array of cellular and biological processes. Three iron-binding glycosyl hydrolase family proteins, along with four CBPs with carbohydrate-binding domains, have been identified as potential effector candidates. These proteins are distinct from the host Solanum lycopersicum proteome. Moreover, they are known to be located extracellularly and function as enzymes that degrade the host cell wall during pathogen-host interactions. The insights gained from this report on the role of metal ions in plant-pathogen interactions can help develop a better understanding of their fundamental biology and control vascular wilt disease in tomato plants.
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Cobre , Proteínas Fúngicas , Fusarium , Hierro , Proteoma , Solanum lycopersicum , Fusarium/metabolismo , Fusarium/química , Proteoma/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Solanum lycopersicum/microbiología , Solanum lycopersicum/metabolismo , Hierro/metabolismo , Cobre/metabolismo , Cobre/química , Proteínas Portadoras/metabolismo , Proteínas Portadoras/química , Proteínas Portadoras/genética , Proteínas de Unión a Hierro/metabolismo , Proteínas de Unión a Hierro/química , Proteínas de Unión a Hierro/genética , Enfermedades de las Plantas/microbiología , Unión ProteicaRESUMEN
Increased expression of target genes that code for proinflammatory chemical mediators results from a series of intracellular cascades triggered by activation of dysregulated NF-κB signaling pathway. Dysfunctional NF-kB signaling amplifies and perpetuates autoimmune responses in inflammatory diseases, including psoriasis. This study aimed to identify therapeutically relevant NF-kB inhibitors and elucidate the mechanistic aspects behind NF-kB inhibition. After virtual screening and molecular docking, five hit NF-kB inhibitors opted, and their therapeutic efficacy was examined using cell-based assays in TNF-α stimulated human keratinocyte cells. To investigate the conformational changes of target protein and inhibitor-protein interaction mechanisms, molecular dynamics (MD) simulations, binding free energy calculations together with principal component (PC) analysis, dynamics cross-correlation matrix analysis (DCCM), free energy landscape (FEL) analysis and quantum mechanical calculations were carried out. Among identified NF-kB inhibitors, myricetin and hesperidin significantly scavenged intracellular ROS and inhibited NF-kB activation. Analysis of the MD simulation trajectories of ligand-protein complexes revealed that myricetin and hesperidin formed energetically stabilized complexes with the target protein and were able to lock NF-kB in a closed conformation. Myricetin and hesperidin binding to the target protein significantly impacted conformational changes and internal dynamics of amino acid residues in protein domains. Tyr57, Glu60, Lys144 and Asp239 residues majorly contributed to locking the NF-kB in a closed conformation. The combinatorial approach employing in silico tools integrated with cell-based approaches substantiated the binding mechanism and NF-kB active site inhibition by the lead molecule myricetin, which can be explored as a viable antipsoriatic drug candidate associated with dysregulated NF-kB.Communicated by Ramaswamy H. Sarma.
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Hesperidina , FN-kappa B , Humanos , FN-kappa B/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Transducción de SeñalRESUMEN
Ligands derived from 2-(1-phenylhydrazinyl)pyridine and salicylaldehyde (HL1), 3-methoxysalicylaldehyde (HL2), 5-bromosalicylaldehyde (HL3), and 3,5-di-tert-butylsalicylaldehyde (HL4) react with [VIVO(acac)2] in MeOH followed by aerial oxidation to give [VVO2(L1)] (1), [VVO2(L2)] (2), [VVO2(L3)] (3), and [VVO2(L4)] (4). Complex [VIVO(acac)(L1)] (5) is also isolable from [VIVO(acac)2] and HL1 in dry MeOH. Structures of all complexes were confirmed by single-crystal X-ray and spectroscopic studies. They efficiently catalyze benzyl alcohol and its derivatives' oxidation in the presence of H2O2 to their corresponding aldehydes. Under optimized reaction conditions using 1 as a catalyst precursor, conversion of benzyl alcohol follows the order: 4 (93%) > 2 (90%) > 1 (86%) > 3 (84%) ≈ 5 (84%). These complexes were also evaluated for antifungal and antiproliferative activities. Complex 3 with MIC50 = 16 µg/mL, 4 with MIC50 = 12 µg/mL, and 5 with MIC50 = 16 µg/mL are efficient toward planktonic cells of Candida albicans and Candida tropicalis. On Michigan cancer foundation-7 (MCF-7) cells, they show comparable cytotoxic effects and exhibit IC50 in the 27.3-33.5 µg/mL range, and among these, 4 exhibits the highest cytotoxicity. A similar study on human embryonic kidney cells (HEK293) confirms their less toxicity at lower concentrations (4 to 16 µg/mL) compared to MCF-7.
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Antifúngicos , Vanadio , Humanos , Vanadio/química , Antifúngicos/farmacología , Peróxido de Hidrógeno/química , Células HEK293 , Alcoholes Bencílicos , LigandosRESUMEN
The MYC transcription factor (TF) has a variety of roles in abiotic stress responses of plants. In the present work, MYC TF named CtMYC (Cymopsis tetragonoloba) from guar plant, which is induced by drought stress, was identified. The mature leaves of guar were employed to detect the full-length CtMYC TF on the 8th day of drought stress. The CtMYC gene showed tissue-specific expression and up regulated under drought stress conditions as compared to the control and maximum expression was observed in mature leaves. Additionally, CtMYC TF was cloned and expressed in E. coli Rosetta cells and CtMYC protein was purified. The circular dichroism (CD) analysis revealed the presence of helical content and beta sheets and in the presence of genomic DNA the conformational changes were observed in secondary structure, which showed DNA binding potential of CtMYC. These results were analyzed by CD and fluorescence studies. In silico studies reveal the presence of conserved bHLH domain and DNA-binding amino acid residues His, Glu and Arg in CtMYC. This is first report on CtMYC TF with DNA binding potential that is responsive to drought. This study provides the structure and characterization of CtMYC TF and DNA binding ability in drought tolerance mechanism in guar.
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Cyamopsis , Factores de Transcripción , Factores de Transcripción/metabolismo , Cyamopsis/genética , Sequías , Escherichia coli/genética , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismoRESUMEN
Fusarium oxysporum f. sp. lycopersici is a soil-borne phytopathogenic species which causes vascular wilt disease in the Solanum lycopersicum (tomato). Due to the continuous competition for zinc usage by Fusarium and its host during infection makes zinc-binding proteins a hotspot for focused investigation. Zinc-binding effector proteins are pivotal during the infection process, working in conjunction with other essential proteins crucial for its biological activities. This work aims at identifying and analysing zinc-binding proteins and zinc-binding proteins effector candidates of Fusarium. We have identified three hundred forty-six putative zinc-binding proteins; among these proteins, we got two hundred and thirty zinc-binding proteins effector candidates. The functional annotation, subcellular localization, and Gene Ontology analysis of these putative zinc-binding proteins revealed their probable role in wide range of cellular and biological processes such as metabolism, gene expression, gene expression regulation, protein biosynthesis, protein folding, cell signalling, DNA repair, and RNA processing. Sixteen proteins were found to be putatively secretory in nature. Eleven of these were putative zinc-binding protein effector candidates may be involved in pathogen-host interaction during infection. The information obtained here may enhance our understanding to design, screen, and apply the zinc-metal ion-based antifungal agents to protect the S. lycopersicum and control the vascular wilt caused by F. oxysporum.
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Fusarium , Proteoma , Fusarium/genética , Transporte BiológicoRESUMEN
Occurrence of non-canonical G-quadruplex (G4) DNA structures in the genome have been recognized as key factors in gene regulation and several other cellular processes. The mosR and ndhA genes involved in pathways of oxidation sensing regulation and ATP generation, respectively, make Mycobacterium tuberculosis (Mtb) bacteria responsible for oxidative stress inside host macrophage cells. Circular Dichroism spectra demonstrate stable hybrid G4 DNA conformations of mosR/ndhA DNA sequences. Real-time binding of mitoxantrone to G4 DNA with an affinity constant ~105-107 M-1, leads to hypochromism with a red shift of ~18 nm, followed by hyperchromism in the absorption spectra. The corresponding fluorescence is quenched with a red shift ~15 nm followed by an increase in intensity. A change in conformation of the G4 DNA accompanies the formation of multiple stoichiometric complexes with a dual binding mode. The external binding of mitoxantrone with a partial stacking with G-quartets and/or groove binding induces significant thermal stabilization, ~20-29 °C in ndhA/mosR G4 DNA. The interaction leads to a two/four-fold downregulation of transcriptomes of mosR/ndhA genes apart from the suppression of DNA replication by Taq polymerase enzyme, establishing the role of mitoxantrone in targeting G4 DNA, as an alternate strategy for effective anti-tuberculosis action in view of deadly multi-drug resistant tuberculosis disease causing bacterial strains t that arise from existing therapeutic treatments.
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G-Cuádruplex , Mycobacterium tuberculosis , Mitoxantrona/farmacología , Mitoxantrona/química , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , ADN/genética , Secuencia de BasesRESUMEN
Wound dressings with outstanding biocompatibility, antimicrobial, and tissue regeneration activities are essential to manage emerging recalcitrant antifungal infections to speed up healing. In this study, we have engineered p-cymene-loaded gellan/PVA nanofibers using electrospinning. Morphological and physicochemical properties of the nanofibers were characterized using a multitude of techniques to validate the successful integration of p-cymene (p-cym). The fabricated nanomaterials exhibited strong antibiofilm activity against Candida albicans and Candida glabrata compared to pure p-cymene. In vitro biocompatibility assay demonstrated that nanofibers did not possess any cytotoxicity to the NIH3T3 cell lines. In vivo, full-thickness excision wound healing study showed that the nanofibers were able to heal skin lesions faster than the conventional clotrimazole gel in 24 days without forming any scar. These findings unraveled p-cymene-loaded gellan gum (GA)/poly(vinyl alcohol) (PVA) nanofibers as an effective biomaterial for cutaneous tissue regeneration.
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Nanofibras , Ratones , Animales , Nanofibras/uso terapéutico , Nanofibras/química , Células 3T3 NIH , Cicatrización de Heridas , BiopelículasRESUMEN
[This corrects the article DOI: 10.1016/j.omtn.2022.11.008.].
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Helicoverpa armigera (Ha), a polyphagous pest, causes significant damage to several crop plants, including cotton. The control of this cosmopolitan pest is largely challenging due to the development of resistance to existing management practices. The Juvenile Hormone (JH) plays a pivotal role in the life cycle of insects by regulating their morphogenetic and gonadotropic development. Hence, enzymes involved in JH biosynthesis are an attractive target for the development of selective insecticides. Farnesyl diphosphate synthase (FPPS), a member protein of (E)-prenyl-transferases, is one of the most crucial enzymes in the biosynthetic pathway of JHs. It catalyzes the condensation of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP), forming farnesyl diphosphate (FPP), a precursor of JH. The study was designed to identify an effective small inhibitory molecule that could inhibit the activity of Helicoverpa armigera - FPPS (HaFPPS) for an effective pest control intervention. Therefore, a 3D model of FPPS protein was generated using homology modeling. The FooDB database library of small molecules was selected for virtual screening, following which binding affinities were evaluated using docking studies. Three top-scored molecules were analyzed for various pharmacophore properties. Further, molecular dynamics (MD) simulation analysis showed that the identified molecules (mitraphylline-ZINC1607834, chlorogenic acid-ZINC2138728 and llagate-ZINC3872446) had a reasonably acceptable binding affinity for HaFPPS and resulted in the formation of a stable HaFPPS-inhibitor(s) complex. The identified phytochemical molecules may be used as potent inhibitors of HaFPPS thus, paving the way for further developing environment-friendly insect growth regulator(s). Communicated by Ramaswamy H. Sarma.
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Geraniltranstransferasa , Mariposas Nocturnas , Animales , Geraniltranstransferasa/química , Geraniltranstransferasa/metabolismoRESUMEN
G-quadruplex is a non-canonical secondary structure identified in the telomeric region and the promoter of many oncogenes. Anthraquinone derivatives, a well-known inducer of telomere disruption in malignant cells and activate the apoptotic pathway. We used biophysical and biochemical studies to confirm the interaction of synthesized anthraquinone derivatives with the human telomeric G-quadruplex sequence. The binding affinity of N-2DEA and N-1DEA are K b = 4.8 × 106 M-1 and K b = 7.6 × 105 M-1, respectively, leading to hypochroism, fluorescence quenching with minor redshift and ellipticity variations indicating ligand binding in the external groove. We found that sodium ions induced stabilization more rather than potassium ions. Molecular docking of complex demonstrates a molecule's exterior binding to a quadruplex. The investigation of ROS activity indicated that the cell initiates mortality in response to the IC50 concentration. Cellular morphology, nuclear condensation, and fragmentation were altered in the treated cell, impairing cellular function. Finally, the transcriptional regulatory study paves the way for drug design as an anti-cancer agent because of the tremendous possibilities of changing substituent groups on anthraquinones to improve efficacy and selectivity for G-quartet DNA. Our research focused on how ligand binding to telomere sequences induces oxidative stress and inhibits the growth of malignant cells.
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Renewable biofuels, such as biodiesel, bioethanol, and biobutanol, serve as long-term solutions to fossil fuel depletion. A sustainable approach feedstock for their production is plant biomass, which is degraded to sugars with the aid of microbes-derived enzymes, followed by microbial conversion of those sugars to biofuels. Considering their global demand, additional efforts have been made for their large-scale production, which is ultimately leading breakthrough research in biomass energy. Metagenomics is a powerful tool allowing for functional gene analysis and new enzyme discovery. Thus, the present article summarizes the revolutionary advances of metagenomics in the biofuel industry and enlightens the importance of unexplored habitats for novel gene or enzyme mining. Moreover, it also accentuates metagenomics potentials to explore uncultivable microbiomes as well as enzymes associated with them.
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Biocombustibles , Metagenómica , Biomasa , AzúcaresRESUMEN
According to current research, anti-cancer anthraquinones impact telomere disruption and may interact with G-quadruplex DNA that triggers signaling to apoptosis. The present study represents the biophysical investigation of oxidative stress, late apoptosis, and induced senescence among cancer cells after binding laboratory synthesized piperidine-based anthraquinone derivatives, 2, 6- Bis [(3-piperidino)acetamido)]anthracene-9,10-dione (N1P) and 2, 6-Bis [piperidino)propionamido]anthracene-9,10-dione (N2P), with G-quadruplex DNA. We employed biophysical approaches to explore the interaction of synthetic anthraquinone derivatives with quadruplex DNA sequences to influence biological activities in the presence of K+ and Na+ cations. The binding affinity for N2P and N1P are Kb = 5.8 × 106 M-1 and Kb = 1.0 × 106 M-1, respectively, leading to hypo-/hyper-chromism with 5-7 nm red shift and significant fluorescence quenching and changes in ellipticity resulting in external binding of both the ligands to G-quadruplex DNA. Ligand binding induced enhancement of thermostability of G4 DNA is greater in Na+ environment (ΔTm = 34 °C) as compared to that in K+ environment (ΔTm = 21 °C), thereby restricting telomerase binding access to telomeres. Microscopic images of treated cells indicated cellular shape, nuclear condensation, and fragmentation alterations. The findings pave the path for therapeutic research, given the great potential of modifying anthraquinone substituent groups towards improved efficacy, ROS generation, and G-quadruplex DNA selectivity.
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G-Cuádruplex , Neoplasias , Telomerasa , Secuencia de Bases , Telómero/genética , Telómero/metabolismo , Antraquinonas/farmacología , Telomerasa/genética , ADN/química , Apoptosis , Antracenos , Neoplasias/tratamiento farmacológico , Neoplasias/genéticaRESUMEN
In the present study, tyrosol-functionalized chitosan gold nanoparticles (Chi-TY-AuNPs) were prepared as an alternative treatment strategy to combat fungal infections. Various biophysical techniques were used to characterize the synthesized Chi-TY-AuNPs. The antifungal and antibiofilm activities of Chi-TY-AuNPs were evaluated against Candida albicans and C. glabrata, and efforts have been made to elucidate the possible mechanism of action. Chi-TY-AuNPs showed a high fungicidal effect against both sessile and planktonic cells of Candida spp. Additionally, Chi-TY-AuNPs completely eradicated (100%) the mature biofilms of both the Candida spp. FESEM analysis highlighted the morphological alterations in Chi-TY-AuNP-treated Candida biofilm cells. The effect of Chi-TY-AuNPs on the ECM components showed significant reduction in protein content in the C. glabrata biofilm and substantial decrease in extracellular DNA content of both the Candida spp. ROS generation analysis using DCFDA-PI staining showed high ROS levels in both the Candida spp., whereas pronounced ROS production was observed in the Chi-TY-AuNP-treated C. glabrata biofilm. Biochemical analysis revealed decreased ergosterol content in Chi-TY-AuNP-treated C. glabrata cells, while inconsequential changes were observed in C. albican s. Furthermore, the transcriptional expression of selected genes (ergosterol biosynthesis, efflux, sterol importer, and glucan biogenesis) was reduced in C. glabrata in response to Chi-TY-AuNPs except ERG11 and CDR1. Conclusively, the result showed the biofilm inhibition and biofilm eradication efficacy of Chi-TY-AuNPs in both the Candida spp. Findings of the present study manifest Chi-TY-AuNPs as a potential therapeutic solution to Candida biofilm-related chronic infections and overcome biofilm antifungal resistance.
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Candida tropicalis is an opportunistic human pathogen with an ability to cause superficial as well as systemic infections in immunocompromised patients. The formation of biofilm by C. tropicalis can cause dreadful and persistent infections which are difficult to treat due to acquired resistance. Presently, available anti-Candida drugs exhibit a high frequency of resistance, low specificity and toxicity at a higher dosage. In addition, the discovery of natural or synthetic anti-Candida drugs is slow paced and often does not pass clinical trials. Citral, a monoterpene aldehyde, has shown effective antimicrobial activities against various microorganisms. However, only few studies have elaborated the action of citral against the biofilm of C. tropicalis. In the present work, the aim was to study the fungicidal effect, differential expression of proteome and changes in extracellular matrix in response to the sub-lethal concentration (16 µg/mL) of citral. The administration of citral on C. tropicalis biofilm leads to a fungicidal effect. Furthermore, the differential expression of proteome has revealed twenty-five proteins in C. tropicalis biofilm, which were differentially expressed in the presence of citral. Among these, amino acid biosynthesis (Met6p, Gln1p, Pha2p); nucleotide biosynthesis (Xpt1p); carbohydrate metabolism (Eno1p, Fba1p, Gpm1p); sterol biosynthesis (Mvd1p/Erg19p, Hem13p); energy metabolism (Dnm1p, Coa1p, Ndk1p, Atp2p, Atp4p, Hts1p); oxidative stress (Hda2p, Gre22p, Tsa1p, Pst2p, Sod2p) and biofilm-specific (Adh1p, Ape1p, Gsp1p) proteins were identified. The overexpression of oxidative stress-related proteins indicates the response of biofilm cell to combating oxidative stress during citral treatment. Moreover, the upregulation of Adh1p is of particular interest because it subsidizes the biofilm inhibition through ethanol production as a cellular response. The augmented expression of Mvd1p/Erg19p signifies the effect of citral on ergosterol biosynthesis. The presence of citral has also shown an increment in hexosamine and ergosterol component in extracellular matrix of C. tropicalis biofilm. Hence, it is indicated that the cellular response towards citral acts through multifactorial processes. This study will further help in the interpretation of the effect of citral on C. tropicalis biofilm and development of novel antifungal agents against these potential protein targets.
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Candida tropicalis , Proteómica , Monoterpenos Acíclicos , Antifúngicos/farmacología , Biopelículas , Candida tropicalis/fisiología , Matriz Extracelular , HumanosRESUMEN
The two major bottlenecks faced during microalgal biofuel production are, (a) higher medium cost for algal cultivation, and (b) cost-intensive and time consuming oil extraction techniques. In an effort to address these issues in the large scale set-ups, this comprehensive review article has been systematically designed and drafted to critically analyze the recent scientific reports that demonstrate the feasibility of microalgae cultivation using wastewaters in outdoor raceway ponds in the first part of the manuscript. The second part describes the possibility of bio-crude oil production directly from wet algal biomass, bypassing the energy intensive and time consuming processes like dewatering, drying and solvents utilization for biodiesel production. It is already known that microalgal drying can alone account for â¼30% of the total production costs of algal biomass to biodiesel. Therefore, this article focuses on bio-crude oil production using the hydrothermal liquefaction (HTL) process that converts the wet microalgal biomass directly to bio-crude in a rapid time period. The main product of the process, i.e., bio-crude oil comprises of C16-C20 hydrocarbons with a reported yield of 50-65 (wt%). Besides elucidating the unique advantages of the HTL technique for the large scale biomass processing, this review article also highlights the major challenges of HTL process such as update, and purification of HTL derived bio-crude oil with special emphasis on deoxygenation, and denitrogenation problems. This state of art review article is a pragmatic analysis of several published reports related to algal crude-oil production using HTL technique and a guide towards a new approach through collaboration of industrial wastewater bioremediation with rapid one-step bio-crude oil production from chlorophycean microalgae.
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The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China's Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae, genus Betacoronavirus, and subgenus Sarbecovirus. As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency's (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100-150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.
Asunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , Inmunidad Colectiva , SARS-CoV-2/inmunología , Proteínas Estructurales Virales/inmunología , Inmunidad Adaptativa , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/clasificación , Humanos , Inmunidad Innata , Vacunación , Desarrollo de VacunasRESUMEN
Fungal infections pose a serious threat to humankind due to the toxicity of conventional antifungal therapy and continuous emerging incidence of multidrug resistance. Essential oils fascinated researchers because of their broad antimicrobial activity and minimal cytotoxicity. However, hydrophobic, volatile and low water solubility of essential oils hinder their applications in pharmaceutical industries. Therefore, in this study we have loaded eucalyptol/ ß-cyclodextrin inclusion complex to gellan/polyvinyl alcohol nanofibers (EPNF) to eradicate Candida albicans and Candida glabrata biofilms. The electrospun nanofibers characterized by various physicochemical techniques and it was observed that EPNF possess highly hydrophilic surface property that facilitate rapid drug release. EPNF inhibited approximately 70% biofilm of C. albicans and C. glabrata. Time kill results depicted that eucalyptol (EPTL) encapsulation in the nanofibers prolonged its antifungal activity than the pure EPTL. Electron microscopy studies revealed that EPNF disrupted the cell surface of Candida. Collectively the current study suggested nanofiber encapsulation enhanced antibiofilm activity of eucalyptol and these nanoscale systems can serve as an alternative therapeutic strategy to treat fungal infections. Further, the developed nanofibrous materials can be applied as cost effective coating agent for biomedical implants.