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COVID-19 is currently considered the ninth-deadliest pandemic, spreading through direct or indirect contact with infected individuals. It has imposed a consistent strain on both the financial and healthcare resources of many countries. To address this challenge, there is a pressing need for the development of new potential therapeutic agents for the treatment of this disease. To identify potential antiviral agents as novel dual inhibitors of SARS-CoV-2, we retrieved 404 alkaloids from 12 selected medicinal antiviral plants and virtually screened them against the renowned catalytic sites and favorable interacting residues of two essential proteins of SARS-CoV-2, namely, the main protease and spike glycoprotein. Based on docking scores, 12 metabolites with dual inhibitory potential were subjected to drug-likeness, bioactivity scores, and drug-like ability analyses. These analyses included the ligand-receptor stability and interactions at the potential active sites of target proteins, which were analyzed and confirmed through molecular dynamic simulations of the three lead metabolites. We also conducted a detailed binding free energy analysis of pivotal SARS-CoV-2 protein inhibitors using molecular mechanics techniques to reveal their interaction dynamics and stability. Overall, our results demonstrated that 12 alkaloids, namely, adouetine Y, evodiamide C, ergosine, hayatinine, (+)-homoaromoline, isatithioetherin C, N,alpha-L-rhamnopyranosyl vincosamide, pelosine, reserpine, toddalidimerine, toddayanis, and zanthocadinanine, are shortlisted as metabolites based on their interactions with target proteins. All 12 lead metabolites exhibited a higher unbound fraction and therefore greater distribution compared with the standards. Particularly, adouetine Y demonstrated high docking scores but exhibited a nonspontaneous binding profile. In contrast, ergosine and evodiamide C showed favorable binding interactions and superior stability in molecular dynamics simulations. Ergosine demonstrated exceptional performance in several key pharmaceutical metrics. Pharmacokinetic evaluations revealed that ergosine exhibited pronounced bioactivity, good absorption, and optimal bioavailability. Additionally, it was predicted not to cause skin sensitivity and was found to be non-hepatotoxic. Importantly, ergosine and evodiamide C emerged as superior drug candidates for dual inhibition of SARS-CoV-2 due to their strong binding affinity and drug-like ability, comparable to known inhibitors like N3 and molnupiravir. This study is limited by its in silico nature and demands the need for future in vitro and in vivo studies to confirm these findings.
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Opisthorchis viverrini is the etiological agent of the disease opisthorchiasis and related cholangiocarcinoma (CCA). It infects fish-eating mammals and more than 10 million people in Southeast Asia suffered from opisthorchiasis with a high fatality rate. The only effective drug against this parasite is Praziquantel, which has significant side effects. Due to the lack of appropriate treatment options and the high death rate, there is a dire need to develop novel therapies against this pathogen. In this study, we designed a multi-epitope chimeric vaccine design against O. viverrini by using immunoinformatics approaches. Non-allergenic and immunogenic MHC-1, MHC-2, and B cell epitopes of three candidate proteins thioredoxin peroxidase (Ov-TPx-1), cathepsin F1 (Ov-CF-1) and calreticulin (Ov-CALR) of O. viverrini, were predicted to construct a potent multiepitope vaccine. The coverage of the HLA-alleles of these selected epitopes was determined globally. Four vaccine constructs made by different adjuvants and linkers were evaluated in the context of their physicochemical properties, antigenicity, and allergenicity. Protein-protein docking and MD simulation found that vaccines 3 was more stable and had a higher binding affinity for TLR2 and TLR4 immune receptors. In-silico restriction cloning of vaccine model led to the formation of plasmid constructs for expression in a suitable host. Finally, the immune simulation showed strong immunological reactions to the engineered vaccine. These findings suggest that the final vaccine construct has the potential to be validated by in vivo and in vitro experiments to confirm its efficacy against the CCA causing O. viverrini.
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Antígenos de Helmintos , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Opistorquíase , Opisthorchis , Vacinas de Subunidades Antigênicas , Opisthorchis/imunologia , Animais , Colangiocarcinoma/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Opistorquíase/imunologia , Opistorquíase/prevenção & controle , Humanos , Neoplasias dos Ductos Biliares/imunologia , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/química , Epitopos de Linfócito B/imunologia , Desenvolvimento de Vacinas , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Proteínas de Helminto/imunologia , Proteínas de Helminto/química , Epitopos de Linfócito T/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Receptor 2 Toll-Like/imunologiaRESUMO
Reaction between the polymeric [RuCl2(CO)2]n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl2(CO)2Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells.
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Aminoquinolinas , Monóxido de Carbono , Complexos de Coordenação , Rutênio , Animais , Camundongos , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Aminoquinolinas/química , Aminoquinolinas/farmacologia , Rutênio/química , Rutênio/farmacologia , Ligantes , Monóxido de Carbono/química , Mioglobina/química , Teoria da Densidade Funcional , LuzRESUMO
This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from â¼0.3 µg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (â¼100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.
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Climate change has brought an alarming situation in the scarcity of fresh water for irrigation due to the present global water crisis, climate variability, drought, increasing demands of water from the industrial sectors, and contamination of water resources. Accurately evaluating the potential of future rice genotypes in large-scale, multi-environment experiments may be challenging. A key component of the accurate assessment is the examination of stability in growth contexts and genotype-environment interaction. Using a split-plot design with three replications, the study was carried out in nine locations with five genotypes under continuous flooding (CF) and alternate wet and dry (AWD) conditions. Utilizing the web-based warehouse inventory search tool (WIST), the water status was determined. To evaluate yield performance for stability and adaptability, AMMI and GGE biplots were used. The genotypes clearly reacted inversely to the various environments, and substantial interactions were identified. Out of all the environments, G3 (BRRI dhan29) had the greatest grain production, whereas G2 (Binadhan-8) had the lowest. The range between the greatest and lowest mean values of rice grain output (4.95 to 4.62 t ha-1) was consistent across five distinct rice genotypes. The genotype means varied from 5.03 to 4.73 t ha-1 depending on the environment. In AWD, all genotypes out performed in the CF system. With just a little interaction effect, the score was almost zero for several genotypes (E1, E2, E6, and E7 for the AWD technique, and E5, E6, E8, and E9 for the CF method) because they performed better in particular settings. The GGE biplot provided more evidence in support of the AMMI study results. The study's findings made it clear that the AMMI model provides a substantial amount of information when evaluating varietal performance across many environments. Out of the five accessions that were analyzed, one was found to be top-ranking by the multi-trait genotype ideotype distance index, meaning that it may be investigated for validation stability measures. The study's findings provide helpful information on the variety selection for the settings in which BRRI dhan47 and BRRI dhan29, respectively, performed effectively in AWD and CF systems. Plant breeders might use this knowledge to choose newer kinds and to design breeding initiatives. In conclusion, intermittent irrigation could be an effective adaptation technique for simultaneously saving water and mitigating GHG while maintaining high rice grain yields in rice cultivation systems.
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Irrigação Agrícola , Mudança Climática , Interação Gene-Ambiente , Genótipo , Oryza , Oryza/genética , Oryza/crescimento & desenvolvimento , Adaptação Fisiológica/genética , SecasRESUMO
Ascorbic acid plays a pivotal role in the human body. It maintains the robustness, enlargement, and elasticity of the collagen triple helix. However, the abnormal concentration of ascorbic acid causes various diseases, such as scurvy, cardiovascular diseases, gingival bleeding, urinary stones, diarrhea, stomach convulsions, etc. In the present work, an iron-doped hydroxyapatite (HAp@Fe2O3)-based biosensor was developed for the colorimetric detection of ascorbic acid based on a low-cost, biocompatible, and ubiquitous material. Due to the catalytic nature of HAp owing to the acidic and basic moieties within the structure, it was used as a template for HAp@Fe2O3 synthesis. This approach provides an active as well as large surface area for the sensing of ascorbic acid. The synthesized platform was characterized by various techniques, such as UV-Vis, FTIR, SEM, XRD, TGA, EDX, etc. The HAp@Fe2O3 demonstrated inherent peroxidase-like activity in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) oxidized with the assistance of H2O2. It resulted in the color changing to blue-green, and after the addition of ascorbic acid, the color changed to colorless, resulting in the reduction of TMB. To achieve optimal sensing parameters, experimental conditions were optimized. The quantity of HAp@Fe2O3, H2O2, pH, TMB, time, and the concentration of ascorbic acid were fine-tuned. The linear range for the proposed sensor was 0.6-56 µM, along with a limit of detection of 0.16 µM and a limit of quantification of 0.53 µM. The proposed sensor detects ascorbic acid within 75 seconds at room temperature. The proposed platform was also applied to quantitatively check the concentration of ascorbic acid in a physiological solution.
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Salinity accumulation poses a threat to the production and productivity of economically important crops such as tomatoes (Solanum lycopersicum L.). Currently, salt tolerance breeding programs have been limited by insufficient genetic and physiological knowledge of tolerance-related traits and a lack of an efficient selection domain. For that purpose, we aimed to determine the ability of tomato cultivars to tolerate salt based on seed traits by multiple biochemical pathways. First, we tested three tomato cultivars according to their response to different sodium chloride (NaCl) concentrations (0, 6.3, 9.8, 13.0, and 15.8 dS m-1) and then we analysed their amino acids, organic acids, and phytohormones. Considering the results of germination traits, it is possible to conclude that cultivar H-2274 was more tolerant to salt stress than others. As a result, multivariate discriminant analysis including principal component analysis and two-way hierarchical clustering analyses were constructed and demonstrated that tomato cultivars were separated from each other by the amino acid, organic acid, and phytohormone contents. Considering germination traits of tomato seeds, cv. 'H-2274' was more tolerant to salinity than others depending on high proline (29 pmol µl-1) and citric acid (568 ng µl-1) assays. Biochemical variability offers a valuable tool for investigating salt tolerance mechanisms in tomatoes, and it will be appreciated to find high-tolerant tomato cultivar(s) to saline conditions. Also, the findings of this study have significant potential for practical applications in agriculture, particularly in developing salt-tolerant tomato cultivars to enhance productivity in saline environments and address socio-economic challenges.
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OBJECTIVES: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan. METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant. RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before. CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.
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Sequenciamento do Exoma , Filaminas , Sinostose , Humanos , Sinostose/genética , Filaminas/genética , Masculino , Feminino , Linhagem , Escoliose/genética , Escoliose/congênito , Anormalidades Múltiplas/genética , Mutação de Sentido Incorreto , Paquistão , Homozigoto , Vértebras Lombares/anormalidades , Doenças Musculoesqueléticas , Vértebras Torácicas/anormalidadesRESUMO
In the current study, seven (7) aurone derivatives (ADs) were synthesized and employed to in-vitro LOX and COX-2 assays, in-vivo models of acetic acid-induced mice writhing, formalin-induced mice paw licking and tail immersion test to evaluate their analgesic potential at the doses of 10 mg and 20 mg/kg body weight. Molecular docking was performed to know the active binding site at both LOX and COX-2 as compared to standard drugs. Among the ADs, 2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one (WE-4)possessed optimal LOX and COX-2 inhibitory strength (IC50=0.30 µM and 0.22 µM) as compared to standard (ZileutonIC50 = 0.08 µM, CelecoxibIC50 = 0.05 µM). Similarly in various pain models compound WE-4 showed significantly (p < 0.05) highest percent analgesic potency as compared to control at a dose of 20 mg/kg i.e. 77.60 % analgesic effect in acetic acid model, 49.97 % (in Phase-1) and 70.93 % (inPhase-2) analgesic effect in formalin pain model and 74.71 % analgesic response in tail immersion model. By the administration of Naloxone, the tail flicking latencies were reversed (antagonized) in all treatments. The WE-4 (at 10 mg/kg and 20 mg/kg) was antagonized after 90 min from 11.23 ± 0.93 and 13.41 ± 1.21 to 5.30 ± 0.48 and 4.80 ± 0.61 respectively as compared to standard Tramadol (from 17.74 ± 1.33 to 3.70 ± 0.48), showing the opiodergic receptor involvement. The molecular docking study of ADs revealed that WE-4 had a higher affinity for LOX and COX-2 with docking scores of -4.324 and -5.843 respectively. As a whole, among the tested ADs, compound WE-4 demonstrated excellent analgesic effects that may have been caused by inhibiting the LOX and COX-2 pathways.
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Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson's, Alzheimer's, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9-35 µM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.
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Phosphodiesterases (PDEs) are vital in signal transduction, specifically by hydrolyzing cAMP and cGMP. Within the PDE family, PDE10A is notable for its prominence in the striatum and its regulatory function over neurotransmitters in medium-spiny neurons. Given the dopamine deficiency in Parkinson's disease (PD) that affects striatal pathways, PDE10A inhibitors could offer therapeutic benefits by modulating D1 and D2 receptor signaling. This study was motivated by the successful history of quinazoline/quinazoline scaffolds in the inhibition of PDE10A. This study involved detailed in silico evaluations through docking followed by pharmacological, pharmacophoric, and pharmacokinetic analyses, prioritizing central nervous system (CNS)-active drug criteria. Seven cyclic peptides, those featuring the quinazoline/quinazoline moiety at both termini, exhibited notably enhanced docking scores compared to those of the remaining alkaloids within the screened library. We identified 7 quinolines and 1 quinazoline including Lepadin G, Aspernigerin, CJ-13536, Aurachin A, 2-Undecyl-4(1H)-quinolone, Huajiaosimuline 3-Prenyl-4-prenyloxyquinolin-2-one, and Isaindigotone that followed the standard CNS active drug criteria. The dominant quinoline ring in our study and its related quinazoline were central to our evaluations; therefore, the pharmacophoric features of these scaffolds were highlighted. The top alkaloids met all CNS-active drug properties; while nonmutagenic and without PAINS alerts, many indicated potential hepatotoxicity. Among the compounds, Huajiaosimuline was particularly significant due to its alignment with lead-likeness and CNS-active criteria. Aspernigerin demonstrated its affinity for numerous dopamine receptors, which signifies its potential to alter dopaminergic neurotransmission that is directly related to PD. Interestingly, the majority of these alkaloids had biological targets primarily associated with G protein-coupled receptors, critical in PD pathophysiology. They exhibit superior excretion parameters and toxicity end-points compared to the standard. Notably, selected alkaloids demonstrated stability in the binding pocket of PDE10A according to the molecular dynamic simulation results. Our findings emphasize the potential of these alkaloids as PDE10A inhibitors. Further experimental studies may be necessary to confirm their actual potency in inhibiting PDE10A before exploring their therapeutic potential in PD.
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The abundance of Panonychus citri McGregor 1916 (Acari: Tetranychidae) and its associated enemies (Euseius stipulatus Athias-Henriot, 1960; Typhlodromus sp.; Phytoseiulus persimilis Athias-Henriot, 1957) was studied on two 12-year-old citrus cultivars, specifically Clementine "Nules" (Citrus Clementina) and Valencia (Citrus sinensis), in the Gharb region of Morocco. Throughout the entire monitoring period in the Valencia late cultivar, the density of the spider mite P. citri on leaves was notably higher at 38.0% (n = 1,212 mobile forms). Predator P. persimilis exhibited a leaf occupancy of 25.0% (n = 812), followed by Typhlodromus sp. at 20.0% (n = 643). Conversely, the abundance of E. stipulatus was lower at 17.0% (n = 538). In the Nules variety, P. citri abundance recorded a higher percentage at 48.0% (n = 1,922). E. stipulatus emerged as the most abundant predator at 23.0% (n = 898), followed by P. persimilis with 16.0% (n = 639). Meanwhile, the population of Typlodromus sp. remained notably low at 13.0% (n = 498). Regarding the fluctuation of the different mites studied on the two cultivars across monitoring dates, the period from May 4 to June 1 was characterized by low temperatures and a diminished presence of mite populations (P. citri, E. stipulatus, Typhlodromus sp., and P. persimilis). However, from June 7 to June 19, characterized by high temperatures, a notable increase in the presence of mite populations was observed. As regards the effect of the variety on the different mites studied, the varietal impact was significant.
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Modern classes of antimicrobials are crucial because most drugs in development today are basically antibiotic derivatives. Even though a large number of metal-based compounds have been studied as antimicrobial agents, relatively few studies have examined the antimicrobial properties of Pd(II) and Pt(II) compounds. The [3+2] cycloaddition reactions of [M(N3)L]PF6 (M = Pd(II) and Pt(II); L = 4'-(2-pyridyl)-2,2':6',2â³-terpyridine) with 4,4,4-trifluoro-2-butynoic acid ethyl ester gave the corresponding triazolate complexes. The reaction products were fully characterized with a variety of analytical and spectroscopic tools including X-ray crystallographic analysis. The crystal structure of [Pd(triazolatoCF3,COOCH2CH3)L]PF6 provided cut-off evidence that the kinetically formed N1-triazolato isomer favoured the isomerization to the thermodynamically stable N2-analogue. The experimental work was complemented with computational work to get an insight into the nature of the predominant triazolate isomer. The lysozyme binding affinity of the triazolate complexes was examined by mass spectrometry. An analysis of the lysozyme Pd(II) adducts suggests a coordinative covalent mode of binding via the loss of the triazolato ligand. The free ligand and its triazolate complexes displayed selective toxicity against Candida albicans and Cryptococcus neoformans, while no cytotoxicity was observed against the normal human embryonic kidney cell line.
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Anti-Infecciosos , Muramidase , Humanos , Anti-Infecciosos/farmacologia , Reação de Cicloadição , Isomerismo , Ligantes , Platina/química , Chumbo/químicaRESUMO
Yersinia pestis, the causative agent of plague, is a gram-negative bacterium that can be fatal if not treated properly. Three types of plague are currently known: bubonic, septicemic, and pneumonic plague, among which the fatality rate of septicemic and pneumonic plague is very high. Bubonic plague can be treated, but only if antibiotics are used at the initial stage of the infection. But unfortunately, Y. pestis has also shown resistance to certain antibiotics such as kanamycin, minocycline, tetracycline, streptomycin, sulfonamides, spectinomycin, and chloramphenicol. Despite tremendous progress in vaccine development against Y. pestis, there is no proper FDA-approved vaccine available to protect people from its infections. Therefore, effective broad-spectrum vaccine development against Y. pestis is indispensable. In this study, vaccinomics-assisted immunoinformatics techniques were used to find possible vaccine candidates by utilizing the core proteome prepared from 58 complete genomes of Y. pestis. Human non-homologous, pathogen-essential, virulent, and extracellular and membrane proteins are potential vaccine targets. Two antigenic proteins were prioritized for the prediction of lead epitopes by utilizing reverse vaccinology approaches. Four vaccine designs were formulated using the selected B- and T-cell epitopes coupled with appropriate linkers and adjuvant sequences capable of inducing potent immune responses. The HLA allele population coverage of the T-cell epitopes selected for vaccine construction was also analyzed. The V2 constructs were top-ranked and selected for further analysis on the basis of immunological, physicochemical, and immune-receptor docking interactions and scores. Docking and molecular dynamic simulations confirmed the stability of construct V2 interactions with the host immune receptors. Immune simulation analysis anticipated the strong immune profile of the prioritized construct. In silico restriction cloning ensured the feasible cloning ability of the V2 construct in the expression system of E. coli strain K12. It is anticipated that the designed vaccine construct may be safe, effective, and able to elicit strong immune responses against Y. pestis infections and may, therefore, merit investigation using in vitro and in vivo assays.
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Peste , Yersinia pestis , Yersinia pestis/imunologia , Yersinia pestis/genética , Humanos , Peste/prevenção & controle , Peste/imunologia , Vacina contra a Peste/imunologia , Vacina contra a Peste/genética , Genoma Bacteriano , Desenvolvimento de Vacinas , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Vacinas Sintéticas/imunologia , AnimaisRESUMO
Reactions between sodium tetrachloropalladate and 2- (or 4-) substituted 4-phenyl-3-thiosemicarbazone ligands (HLR), with various electron-donating and electron-withdrawing substituents (R = OCH3, NO2, and Cl), afford square-planar complexes of the general formula [Pd(LR)2]. Ground-state geometry optimization and the vibrational analysis of cis- and trans-isomers of the complexes were carried out to get an insight into the stereochemistry of the complexes. Natural bond orbital analysis was used to analyze how the nature of the substituent affects the natural charge of the metal center, the type of hybridization, and the strength of the M-N and M-S bonds. Using spectrophotometry, the stability of the complexes, and their DNA binding abilities were assessed. The Pd(II) complexes showed moderate cytotoxicity against MCF-7 and Caco-2â cell lines, two of the assessed malignant cell lines, resulting in all known cell death types, including early apoptotic bodies and late apoptotic vacuoles as well as evident necrotic bodies.
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Antineoplásicos , Complexos de Coordenação , Paládio , Tiossemicarbazonas , Humanos , Paládio/química , Paládio/farmacologia , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Ligantes , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Células MCF-7 , Estrutura Molecular , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Relação Estrutura-Atividade , DNA/química , DNA/metabolismo , DNA/efeitos dos fármacosRESUMO
Diabetes, also known as diabetes mellitus (DM), is a metabolic disorder characterized by an abnormal rise in blood sugar (glucose) levels brought on by a complete or partial lack of insulin secretion along with corresponding changes in the metabolism of lipids, proteins, and carbohydrates. It has been reported that medicinal plants play a pivotal role in the treatment of various ailments such as diabetes mellitus, dyslipidemia, and hypertension. The current study involved exploring the acute toxicity and in vivo antidiabetic activity of berberine (WA1), palmatine (WA2), and 8-trichloromethyl dihydroberberine (WA3) previously isolated from Berberis glaucocarpa Stapf using a streptozotocin (STZ)-induced diabetic rat model. Body weight and blood glucose level were assessed on a day interval for 4 weeks. Biochemical parameters, antioxidant enzymes, and oxidative stress markers were also determined. In an acute toxicity profile, the WA1, WA2, and WA3 were determined to be nontoxic up to 500 mg/kg (b.w). After the second and third weeks of treatment (14 and 21 days), the blood glucose levels in the WA1-, WA2-, and WA3-treated groups were significantly lower than those in the diabetic control group (476.81 ± 8.65 mg/dL, n = 8, P < 0.001). On the 21st day, there was a decrease in the blood glucose level and the results obtained were 176.33 ± 4.69, 197.21 ± 4.80, and 161.99 ± 4.75 mg/dL (n = 8, P < 0.001) for WA1, WA2, and WA3 at 12 mg/kg, respectively, as opposed to the diabetic control group (482.87 ± 7.11 mg/dL, n = 8, P < 0.001). Upon comparison with the diabetic group at the end of the study (28 days), a substantial drop in the glucose level of WA3 at 12 mg/kg (110.56 ± 4.11 mg/dL, n = 8, P < 0.001) was observed that was almost near the values of the normal control group. The treated groups (WA1, WA2, and WA3) treated with the samples displayed a significant decline in the levels of HbA1c. Treatment of the samples dramatically lowered the lipid level profile. In groups treated with samples, plasma levels of triglycerides, total cholesterol, and LDL were significantly lowered [F (5, 42) = 100.6, n = 8, P < 0.001]; these levels were also significantly decreased [F (5, 42) = 129.6 and 91.17, n = 8, P < 0.001]. In contrast to the diabetes group, all treated groups had significantly higher HDL levels [F (5, 42) = 15.46, n = 8, P < 0.001]. As a result, hypolipidemic activity was anticipated in the samples. In addition to that, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was considerably elevated in the groups treated with the sample compared to the diabetic control group (n = 8, P < 0.001).
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The existence of antibiotics in the environment has recently raised serious concerns about their possible hazards to human health and the water ecosystem. In the current study, an activated carbon-supported nanocomposite, AC-CoFe2O3, was synthesized by a coprecipitation method, characterized, and then applied to adsorb different drugs from water. The synthesized composites were characterized by using energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller plots, and scanning electron microscopy. The adsorption of both Ciprofloxacin (Cipro) and Amoxicillin (Amoxi) antibiotics on the composite followed the pseudo-second-order kinetic model (R2 = 0.9981 and 0.9974 mg g-1 min-1, respectively). Langmuir isotherm was the best-fit model showing 312.17 and 217.76 mg g-1 adsorption capacities for Ciprofloxacin and Amoxicillin, respectively, at 333 K. The negative Gibbs free energy (ΔG°) specified the spontaneity of the method. The positive change in the enthalpy (ΔH) indicated that the adsorption process was assisted by higher temperatures. The different optimized parameters were pH, contact time, adsorbent weight, concentration, and temperature. The maximum adsorption of Cipro was found to be 98.41% at pH 12, while for Amoxi, it was 89.09% at pH 2 at 333 K. The drugs were then successfully determined from natural water samples at optimized conditions using these nanocomposites.
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The objective of the study was to extend shelf life of Vitis vinifera (L.) by the application of green synthesized Magnesium oxide nanoparticles. Aqueous leaf extract of Azadirachta indica A. juss. and various concentrations of 20 mM, 30 mM, and 40 mM solutions of Magnesium nitrate hexa hydrate salt, were used to synthesize nanoparticles of different size. The characterization of nanoparticles was done by SEM, XRD, and UV. The antimicrobial activity of MgO NPs was evaluated for Azospirilum brasilense and Trichoderma viride, representative of microbes responsible for V. vinifera fruits spoilage. Nanoparticles with crystal size of 28.60 nm has more pronounced effect against microbes. The Shelf life of the Vitis vinifera L. was evaluated by application of 28.60 nm MgO NPs through T1 (nanoparticles coated on packaging), T2 (nanoparticles coated directly on fruit) at 4 °C and 25 °C. T1 at 4 °C was effective to extend the shelf life of Vitis vinifera (L) for an average of 20 days.
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Nitrogen (N) is one of the most crucial elements for plant growth. However, a deficiency of N affects plant growth and development. Wedelia trilobata is a notorious invasive plant species that exhibits superior tolerance to adapt to environmental stresses. Yet, research on the growth and antioxidant defensive system of invasive Wedelia under low N stress, which could contribute to understanding invasion mechanisms, is still limited. Therefore, this study aims to investigate and compare the tolerance capability of invasive and native Wedelia under low and normal N conditions. Native and invasive Wedelia species were grown in normal and low-N conditions using a hydroponic nutrient solution for 8 weeks to assess the photosynthetic parameters, antioxidant activity, and localization of reactive oxygen species (ROS). The growth and biomass of W. trilobata were significantly (p < 0.05) higher than W. chinensis under low N. The leaves of W. trilobata resulted in a significant increase in chlorophyll a, chlorophyll b, and total chlorophyll content by 40.2, 56.2, and 46%, respectively, compared with W. chinensis. W. trilobata significantly enhanced antioxidant defense systems through catalase, peroxidase, and superoxide dismutase by 18.6%, 20%, and 36.3%, respectively, providing a positive response to oxidative stress caused by low N. The PCA analysis showed that W. trilobata was 95.3% correlated with physiological traits by Dim1 (79.1%) and Dim2 (16.3%). This study provides positive feedback on W. trilobata with respect to its comprehensive invasion mechanism to improve agricultural systems via eco-friendly approaches in N deficit conditions, thereby contributing to the reclamation of barren land.
RESUMO
Stress is one of the important factors that directly or indirectly affects the plant architecture, biochemical pathways, and growth and development. Melatonin (MEL) is an important stress hormone; however, the exogenous addition of melatonin to culture media stimulates the defense mechanism and releases higher quantities of secondary metabolites. In this study, submerged adventitious root cultures (SARCs) of diabetically important Stevia rebaudiana were exposed to variable concentrations (0.5-5.0 mg/L) of MEL in combination with 0.5 mg/L naphthalene acetic acid (NAA) to investigate the biomass accumulation during growth kinetics with 07 days intervals for a period of 56 days. The effects of exogenous MEL on the biosynthesis of stevioside (Stev.), total phenolics content (TPC), total flavonoids content (TFC), total phenolics production (TPP), total flavonoids production (TFP), total polyphenolics content (TPPC), fresh and dry weight (FW & DW), and antioxidant potential were also studied. Most of the SARCs displayed lag, exponential, stationary, and decline phases with variable biomass accumulation. The maximum fresh (236.54 g/L) and dry biomass (28.64 g/L) was observed in SARCs exposed to 3.0 mg/L MEL and 0.5 mg/L NAA. The same combination of MEL and NAA also enhanced the accumulation of TPC (18.96 mg/g-DW), TFC (6.33 mg/g-DW), TPP (271.51 mg/L), TFP (90.64 mg/L), and TPPC (25.29 mg/g-DW). Similarly, the highest stevioside biosynthesis (91.45 mg/g-DW) and antioxidant potential (86.15%) were observed in SARCs exposed to 3.0 mg/L MEL and NAA. Moreover, a strong correlation was observed between the biomass and the contents of phenolics, flavonoids, antioxidants, and stevioside. These results suggest that MEL is one of multidimensional stress hormones that modulate the biosynthetic pathways to release higher quantities of metabolites of interest for various industrial applications.