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Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity of the 7-transmembrane protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. A central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Cholesterol activity in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability.
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Colesterol/metabolismo , Proteínas Hedgehog/metabolismo , Receptor Patched-1/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Microscopia Crioeletrônica , Dimerização , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Evolução Molecular , Células HEK293 , Proteínas Hedgehog/química , Proteínas Hedgehog/genética , Humanos , Camundongos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/química , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Receptor Patched-1/química , Receptor Patched-1/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Alinhamento de Sequência , Transdução de SinaisRESUMO
Membrane lipids control the cellular activity of kinases containing the Src homology 2 (SH2) domain through direct lipid-SH2 domain interactions. Here we report development of new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction that block the cellular activity of their host proteins. As a pilot study, we evaluated the efficacy of lipid-SH2 domain interaction inhibitors for spleen tyrosine kinase (Syk), which is implicated in hematopoietic malignancies, including acute myeloid leukemia (AML). An optimized inhibitor (WC36) specifically and potently suppressed oncogenic activities of Syk in AML cell lines and patient-derived AML cells. Unlike ATP-competitive Syk inhibitors, WC36 was refractory to de novo and acquired drug resistance due to its ability to block not only the Syk kinase activity, but also its noncatalytic scaffolding function that is linked to drug resistance. Collectively, our study shows that targeting lipid-protein interaction is a powerful approach to developing new small molecule drugs.
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Leucemia Mieloide Aguda , Proteínas Tirosina Quinases , Humanos , Proteínas Tirosina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Projetos Piloto , Domínios de Homologia de src , Fosforilação , Leucemia Mieloide Aguda/tratamento farmacológico , Lipídeos , Quinase Syk/metabolismoRESUMO
Reductions in red to far-red ratio (R:FR) provide plants with an unambiguous signal of vegetational shade and are monitored by phytochrome photoreceptors. Plants integrate this information with other environmental cues to determine the proximity and density of encroaching vegetation. Shade-sensitive species respond to reductions in R:FR by initiating a suite of developmental adaptations termed shade avoidance. These include the elongation of stems to facilitate light foraging. Hypocotyl elongation is driven by increased auxin biosynthesis promoted by PHYTOCHROME INTERACTING FACTORs (PIF) 4, 5 and 7. UV-B perceived by the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor rapidly inhibits shade avoidance, in part by suppressing PIF4/5 transcript accumulation and destabilising PIF4/5 protein. Here, we show that longer-term inhibition of shade avoidance is sustained by ELONGATED HYPOCOTYL 5 (HY5) and HY5 HOMOLOGUE (HYH), which regulate transcriptional reprogramming of genes involved in hormone signalling and cell wall modification. HY5 and HYH are elevated in UV-B and suppress the expression of XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASE (XTH) genes involved in cell wall loosening. They additionally increase expression GA2-OXIDASE1 (GA2ox1) and GA2ox2, encoding gibberellin catabolism enzymes that act redundantly to stabilise the PIF-inhibiting DELLA proteins. UVR8 therefore regulates temporally distinct signalling pathways to first rapidly inhibit and subsequently maintain suppression of shade avoidance following UV-B exposure.
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Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Transdução de Sinais/fisiologia , Plantas/metabolismo , Fitocromo/metabolismo , Hipocótilo/genética , Hipocótilo/metabolismo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismoRESUMO
Renewable energy sources, such as wind, tide, solar cells, etc, are the primary research areas that deliver enormous amounts of energy for our daily usage and minimize the dependency upon fossil fuel. Paralley, harnessing ambient energy from our surroundings must be prioritized for small powered systems. Nanogenerators, which use waste energy to generate electricity, are based on such concepts. We refer to these nanogenerators as energy harvesters. The purpose of energy harvesters is not to outcompete traditional renewable energy sources. It aims to reduce reliance on primary energy sources and enhance decentralized energy production. Energy storage is another area that needs to be explored for quickly storing the generated energy. Supercapacitor is a familiar device with a unique quick charging and discharging feature. Encouraging advancements in energy storage and harvesting technologies directly supports the efficient and comprehensive use of sustainable energy. Yet, self-optimization from independent energy harvesting and storage devices is challenging to overcome. It includes instability, insufficient energy output, and reliance on an external power source, preventing their direct application and future development. Coincidentally, integrating energy harvesters and storage devices can address these challenges, which demand their inherent action. This review intends to offer a complete overview of supercapacitor-based integrated energy harvester and storage systems and identify opportunities and directions for future research in this subject.
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Heavy metal pollution in soil has emerged as a major environmental concern. This can be attributed to human activities such as mining, modern agriculture, and industrialization. This study was conducted to determine how heavy metals spread from mine tailings to surrounding farmland. Metal absorption and accumulation were also investigated in the root and shoot biomass of tapioca crops grown in those farmlands. Metal concentrations in MTAS1 were 85.3 ± 1.2, 45.8 ± 1.5, 134.8 ± 1.7, 92.4 ± 2.2, and 78.95 ± 1.4 mg kg-1, respectively. Heavy metal concentrations in MTAS2 and MTAS3 were found to be 79.62 ± 1.6, 75.4 ± 1.5, 41.31 ± 1.1, 47.8 ± 1.6, 142.5 ± 2.1, 128.4 ± 1.4, 86.2 ± 1.9, 79.5 ± 1.3, and 83.4 ± 1.2 mg kg-1, respectively. Tapioca crop shoot and root biomass grown at these metal polluted sites absorbed and accumulated significant amounts of Cd, Cu, Zn, Pb, Ni, and Mn. Notably, the metal content of the tapioca crop's root and shoot biomass exceeded national standards.
Assuntos
Biomassa , Metais Pesados , Mineração , Raízes de Plantas , Brotos de Planta , Poluentes do Solo , Metais Pesados/análise , Metais Pesados/metabolismo , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Manihot/crescimento & desenvolvimento , Manihot/metabolismo , Manihot/química , Agricultura/métodos , Monitoramento AmbientalRESUMO
The antimicrobial, antidiabetic, and anti-inflammatory activities efficiency of Aerva lanata plant extracts (aqueous (Aqu-E), acetone (Ace-E), and ethanol (Eth-E)) were investigated in this study. Furthermore, the active molecules exist in the crude extract were characterized by UV-Visible spectrophotometer, Fourier transform infrared (FTIR), High-performance liquid chromatography (HPLC), and Gas Chromatography-Mass Spectrometry (GC-MS) analyses. The preliminary phytochemical study revealed that the Ace-E restrain more phytochemicals like alkaloids, saponins, anthraquinone, tannins, phenolics, flavonoids, glycosides, terpenoids, amino acid, steroids, protein, coumarin, as well as quinine than Aqu-E and Eth-E. Accordingly to this Ace-E showed considerable antimicrobial activity as the follows: for bacteria S. aureus > E. coli > K. pneumoniae > P. aeruginosa > B. subtilis and for fungi T. viride > A.flavus > C. albicans > A.niger at 30 mg ml concentration. Similarly, Ace-E showed considerable antidiabetic (α-amylase: 71.7 % and α-glucosidase: 70.1 %) and moderate anti-inflammatory (59 % and 49.8 %) activities. The spectral and chromatogram studies confirmed that the Ace-E have pharmaceutically valuable bioactive molecules such as (Nbutyl)-octadecane, propynoic acid, neophytadiene, and 5,14-di (N-butyl)-octadecane. These findings suggest that Ace-E from A. lanata can be used to purify additional bioactive substances and conduct individual compound-based biomedical application research.
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Alcanos , Amaranthaceae , Anti-Infecciosos , Acetona , Hipoglicemiantes , Escherichia coli , Staphylococcus aureus , Amaranthaceae/química , Antioxidantes , AntibacterianosRESUMO
In this study, we studied the hydrocracking of waste chicken oil (WCO) catalyzed by mesoporous SO42-/KIT-6. The study included WCO extraction, SO42-/KIT-6 catalyst synthesis, hydrocracking, and catalytic characterization. XRD patterns revealed intense peaks in the low-angle region, with shoulder peaks showing an increase in sulphate loading from 10% to 30%. The BET-specific surface area for the pure KIT-6 supports measured at 1003 m2/g, indicative of a well-defined mesoporous structure. Thermogravimetric analysis (TGA) showed a two-stage weight loss, attributed to the elimination of hydrated water (about 200 °C) and decomposition of sulphate ions (400-450 °C). SEM analysis highlighted the surface morphology of the active SK-2 catalyst. Hydrocatalytic and catalytic cracking reactions were performed, and about 99.8% conversion was achieved with 20 mL/H H2 flow, whereas higher production of bioliquids was observed at a flow of 15 mL/h. The hydrocracking mechanism was also studied to understand the formation of lower hydrocarbons. GC analyses of simulated distilled gasoline, kerosene, and diesel showed diverse hydrocarbon compositions. For engine testing, non-hydrocracked fuel rose to 28 kW at 3000 rpm and declined to 21 kW at 3500 rpm. Emission analysis revealed decreasing trends in NOX emissions of hydrogen-rich blends, with values of 65 ppm, 54 ppm, and 48 ppm for petrol, NHBL, and HBL, respectively. Similarly, SO2 emissions reduced from petrol to NHBL and HBL at 910 ppm, 800 ppm, and 600 ppm, respectively, suggesting reduced environmental impact. CO emissions exhibited a substantial reduction in NHBL (0.90%) and HBL (0.54%) compared to petrol (2.70%), emphasizing the cleaner combustion characteristics. Our results provide a comprehensive exploration of waste chicken oil hydrocracking, emphasizing catalyst synthesis, fuel characterization, engine performance, and environmental impact, thereby contributing valuable insights to the field of sustainable bioenergy.
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Galinhas , Animais , Catálise , Óleos/químicaRESUMO
Ruminants release enteric methane into the atmosphere, significantly increasing greenhouse gas emissions and degrading the environment. A common focus of traditional mitigation efforts is on dietary management and manipulation, which may have limits in sustainability and efficacy, exploring the potential of essential microorganisms as a novel way to reduce intestinal methane emissions in ruminants; a topic that has garnered increased attention in recent years. Fermentation and feed digestion are significantly aided by essential microbes found in the rumen, such as bacteria, fungi, and archaea. The practical implications of the findings reported in various studies conducted on rumen gut concerning methane emissions may pave the way to understanding the mechanisms of CH4 production in the rumen to enhance cattle feed efficiency and mitigate CH4 emissions from livestock. This review discussed using essential bacteria to reduce intestinal methane emissions in ruminants. It investigates how particular microbial strains or consortia can alter rumen fermentation pathways to lower methane output while preserving the health and productivity of animals. We also describe the role of probiotics and prebiotics in managing methane emissions using microbial feed additives. Further, recent studies involving microbial interventions have been discussed. The use of new methods involving functional metagenomics and meta-transcriptomics for exploring the rumen microbiome structure has been highlighted. This review also emphasizes the challenges faced in altering the gut microbiome and future directions in this area.
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Cost is the crucial impediment in commercializing microalgal biodiesel. Therefore, cultivating microalgae in cost-effective nutrients reduces the upstream process cost remarkably. Thus, in this study, sugar cane bagasse hydrolysate (SBH) as a lucrative carbon supplement for Chlorococcum sp. and subsequent lipid extraction via an optimized solvent system for biodiesel production was investigated. Characterization of SBH revealed the presence of various monosaccharides and other sugar derivatives such as glucose, fructose, xylose, arabinose, etc. The maximum dry cell weight of 1.7 g/L was estimated in cultures grown in 10 mL SBH. Different solvents such as diethyl ether (DEE), chloroform (CHL), ethyl acetate (ETA), hexane (HEX), methanol (MET), ethanol (ETOH), acetone (ACE) and also combination of solvents (2:1 ratio) such as DEE: MET, CHL: MET, HEX: MET, HEX: ETOH was tested for lipid extraction efficacy. Among solvents used, 12.3% and 18.4% of lipids were extracted using CHL and CHL: MET, respectively, from 10 mL SBH amended cultures. However, the biodiesel yield was found to be similar at about 70.16 % in both SBH and no SBH-added cultures. The fatty acid profile of the biodiesel shows palmitic, oleic, linoleic, linolenic, and arachidonic acid as principal fatty acids. Further, the levels of SFAs, MUFAs, and PUFAs in 10 mL SBH-added cells were 24.67, 12.89, and 34.24%, respectively. Eventually, the fuel properties of Chlorococcum sp. biodiesel, satisfying international biodiesel standards, make the biodiesel a viable diesel substitute in the future.
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Microalgas , Saccharum , Ácidos Graxos , Solventes , Lipídeos , Biocombustíveis , Carbono , Metanol , BiomassaRESUMO
Cu2ZnSnS4 (CZTS) was synthesized following hot injection method and the process was optimized by varying temperature conditions. Four samples at different temperatures viz., 200, 250, 300 and 350 °C were prepared and analyzed using different characterization techniques. Based on the correlation between XRD, Raman and XPS, we conclude that the formation of ZnS and SnS2 occurs at 350 °C but at 200 °C there is no breakdown of the complex as per XRD. According to Raman and XPS analysis, as the temperature rises, the bonds between the metals become weaker, which is visibly seen in Raman and XPS due to the minor peaks of copper sulfide. Scanning electron microscopic analysis confirmed nanometric particles which increase in size with temperature. The photocatalytic evaluation showed that CZTS synthesized at 200 °C performed efficiently in the removal of the two colorants, methylene blue and Rhodamine 6G, achieving 92.80% and 90.65%, respectively. The photocatalytic degradation efficiencies decreased at higher temperatures due to bigger sized CZTS particles as confirmed by SEM results. Computational simulations confirm that CZTS has a highly negative energy -25,764 Ry, confirming its structural stability and higher covalent than ionic character.
Assuntos
Cobre , Azul de Metileno , Rodaminas , Sulfetos , Rodaminas/química , Azul de Metileno/química , Sulfetos/química , Cobre/química , Catálise , Compostos de Estanho/química , Temperatura Alta , Poluentes Químicos da Água/químicaRESUMO
Shade-avoiding plants can detect the presence of neighboring vegetation and evoke escape responses before canopy cover limits photosynthesis. Rapid stem elongation facilitates light foraging and enables plants to overtop competitors. A major regulator of this response is the phytochrome B photoreceptor, which becomes inactivated in light environments with a low ratio of red to far-red light (low R:FR), characteristic of vegetational shade. Although shade avoidance can provide plants with a competitive advantage in fast-growing stands, excessive stem elongation can be detrimental to plant survival. As such, plants have evolved multiple feedback mechanisms to attenuate shade-avoidance signaling. The very low R:FR and reduced levels of photosynthetically active radiation (PAR) present in deep canopy shade can, together, trigger phytochrome A (phyA) signaling, inhibiting shade avoidance and promoting plant survival when resources are severely limited. The molecular mechanisms underlying this response have not been fully elucidated. Here, we show that Arabidopsis thaliana phyA elevates early-evening expression of the central circadian-clock components TIMING OF CAB EXPRESSION 1 (TOC1), PSEUDO RESPONSE REGULATOR 7 (PRR7), EARLY FLOWERING 3 (ELF3), and ELF4 in photocycles of low R:FR and low PAR. These collectively suppress stem elongation, antagonizing shade avoidance in deep canopy shade.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Relógios Circadianos , Fitocromo A/metabolismo , Folhas de Planta/fisiologia , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Relógios Circadianos/efeitos da radiação , Ritmo Circadiano/efeitos da radiação , Regulação da Expressão Gênica de Plantas , Luz , Folhas de Planta/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Microplastics are found ubiquitous in the natural environment and are an increasing source of worry for global health. Rapid industrialization and inappropriate plastic waste management in our daily lives have resulted in an increase in the amount of microplastics in the ecosystem. Microplastics that are <150 µm in size could be easily ingested by living beings and cause considerable toxicity. Microplastics can aggregate in living organisms and cause acute, chronic, carcinogenic, developmental, and genotoxic damage. As a result, a sustainable approach to reducing, reusing, and recycling plastic waste is required to manage microplastic pollution in the environment. However, there is still a significant lack of effective methods for managing these pollutants. As a result, the purpose of this review is to convey information on microplastic toxicity and management practices that may aid in the reduction of microplastic pollution. This review further insights on how plastic trash could be converted as value-added products, reducing the load of accumulating plastic wastes in the environment, and leading to a beneficial endeavor for humanity.
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Poluentes Ambientais , Poluentes Químicos da Água , Microplásticos , Plásticos , Ecossistema , Poluição Ambiental/prevenção & controle , Poluentes Químicos da Água/análise , Monitoramento AmbientalRESUMO
UV-B radiation regulates numerous morphogenic, biochemical and physiological responses in plants, and can stimulate some responses typically associated with other abiotic and biotic stimuli, including invertebrate herbivory. Removal of UV-B from the growing environment of various plant species has been found to increase their susceptibility to consumption by invertebrate pests, however, to date, little research has been conducted to investigate the effects of UV-B on crop susceptibility to field pests. Here, we report findings from a multi-omic and genetic-based study investigating the mechanisms of UV-B-stimulated resistance of the crop, Brassica napus (oilseed rape), to herbivory from an economically important lepidopteran specialist of the Brassicaceae, Plutella xylostella (diamondback moth). The UV-B photoreceptor, UV RESISTANCE LOCUS 8 (UVR8), was not found to mediate resistance to this pest. RNA-Seq and untargeted metabolomics identified components of the sinapate/lignin biosynthetic pathway that were similarly regulated by UV-B and herbivory. Arabidopsis mutants in genes encoding two enzymes in the sinapate/lignin biosynthetic pathway, CAFFEATE O-METHYLTRANSFERASE 1 (COMT1) and ELICITOR-ACTIVATED GENE 3-2 (ELI3-2), retained UV-B-mediated resistance to P. xylostella herbivory. However, the overexpression of B. napus COMT1 in Arabidopsis further reduced plant susceptibility to P. xylostella herbivory in a UV-B-dependent manner. These findings demonstrate that overexpression of a component of the sinapate/lignin biosynthetic pathway in a member of the Brassicaceae can enhance UV-B-stimulated resistance to herbivory from P. xylostella.
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Arabidopsis , Brassica napus , Mariposas , Animais , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Brassica napus/genética , Herbivoria , Lignina , Mariposas/fisiologia , PlantasRESUMO
Nanoparticles synthesis from green chemistry method is gaining a lot of attention due to their non-toxic, low cost and facile. In this study, a copper oxide nanoparticle (CuO NPs) was synthesized using Sida cordifolia aqueous leaf extract and incorporated chitosan biomolecules to potential enhancing of biological properties. The CuO NPs and chitosan (CS) embedded nanocomposite was noted as CuO-CS nanocomposite, its was physicochemical characterized by using of UV-Visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray Diffraction (XRD) and Field emission scanning electron microscopy (FE-SEM) with Energy dispersive X-ray (EDX) analysis. Bio-functionalized CuO-CS nanocomposite was performed antibacterial efficiency against both Gram positive (Staphylococcus aureus, Bacillus subtilis) and Gram negative (Salmonella typhi, Escherichia coli) bacteria through the Mueller Hinton agar (MHA) well diffusion techniques. The highest bactericidal activity was revealed Gram positive of B. subtilis and Gram negative of S. typhi bacteria, respectively. Further, the cytotoxicity effect of biosynthesized nanocomposite was an examined against human breast cancer MDA-MB-231 and lung cancer A549 cell lines. The half maximal inhibitory concentration is showed at 2 µg/mL for MDA-MB-231and 4 µg/mL was A549 cells. Live/dead cells were detected by fluorescence microscopic observation at the IC50 concentration. In furthermore, bio-functionalized CuO-CS nanocomposite was performed photocatatlytic dye degradation against for industrial dyes of crystal violet (CV) and malachite green (MG). From the results, synergic bio-functionalized CuO-CS nanocomposite was suggested potential suitable for biomedical applications as well as industrial wastewater treatment.
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Quitosana , Neoplasias Pulmonares , Nanopartículas Metálicas , Nanocompostos , Humanos , Quitosana/química , Cobre/química , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/química , Nanocompostos/química , Bactérias , Neoplasias Pulmonares/tratamento farmacológico , Água , Linhagem Celular , Testes de Sensibilidade Microbiana , Difração de Raios X , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/químicaRESUMO
KEY MESSAGE: Plant regulatory noncoding RNAs (ncRNAs) have emerged as key modulators of gene expression during callus induction. Their further study may promote the design of innovative plant tissue culture protocols. The use of plants by humans has recently taken on a new and expanding insight due to the advent of genetic engineering technologies. In this context, callus cultures have shown remarkable potential for synthesizing valuable biomolecules, crop improvement, plant micropropagation, and biodiversity preservation. A crucial stage in callus production is the conversion of somatic cells into totipotent cells; compelling evidence indicates that stress factors, transcriptional regulators, and plant hormones can trigger this biological event. Besides, posttranscriptional regulators of gene expression might be essential participants in callus induction. However, research related to the analysis of noncoding RNAs (ncRNAs) that modulate callogenesis and plant cell dedifferentiation in vitro is still at an early stage. During the last decade, some relevant studies have enlightened the fact that different classes of ncRNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and long noncoding RNAs (lncRNAs) are implicated in plant cell dedifferentiation through regulating the expression levels of diverse gene targets. Hence, understanding the molecular relevance of these ncRNAs in the aforesaid biological processes might represent a promising source of new biotechnological approaches for callus culture and plant improvement. In this current work, we review the experimental evidence regarding the prospective roles of ncRNAs in callus induction and plant cell dedifferentiation to promote this field of study.
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MicroRNAs , RNA Longo não Codificante , Humanos , Desdiferenciação Celular/genética , RNA não Traduzido/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Interferente Pequeno/genética , RNA Longo não Codificante/genética , Plantas/genéticaRESUMO
Despite significant progress in early detection and treatment, a few aggressive breast cancers still exhibit resistance to therapy. This study aimed to identify a therapeutic target for radioresistant breast cancer (RRbc) through a protein network from breast cancer genes and to evaluate potent phytochemicals against the identified target. Our approach includes the integration of differential expression genes from expression datasets to create a protein network and to use survival analysis to identify the crucial RRbc protein in order to discover a therapeutic target. Next, the phytochemicals sourced from brown algae were screened through molecular docking, ADME (absorption, distribution, metabolism, and excretion), molecular dynamics (MD) simulation, MM-GBSA, and quantum mechanics against the identified target. As a result of our protein network investigation, the proto-oncogene c-KIT (KIT) protein was identified as a potent radioresistant breast cancer target. Further, phytochemical screening establishes that nahocol-A1 from brown algae has high binding characteristics (-8.56 kcal/mol) against the KIT protein. Then, quantum chemical analysis of nahocol-A1 provided insights into its electronic properties favorable for protein binding. Also, MD simulation comprehends the conformational stability of the KIT-nahocol-A1 complex. Overall, our findings suggest nahocol-A1 could serve as a promising therapeutic candidate for radioresistant breast cancer.
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Neoplasias , Phaeophyceae , Simulação de Acoplamento Molecular , Cromatografia Gasosa , Simulação de Dinâmica MolecularRESUMO
Zinc ferrite nanoparticles (ZFO NPs) are a promising magneto-crystalline platform for nanomedicine-based cancer theranostics. ZFO NPs synthesized using co-precipitation method are characterized using different techniques. UV-visible spectroscopy exhibits absorption peaks specific for ZFO. Raman spectroscopy identifies Raman active, infrared active, and silent vibrational modes while Fourier transforms infrared spectroscopic (FTIR) spectra display IR active modes that confirm the presence of ZFO. X-ray diffraction pattern (XRD) exhibits the crystalline planes of single-phase ZFO with a face-centered cubic structure that coincides with the selected area electron diffraction pattern (SAED). The average particle size according to high-resolution transmission electron microscopy (HR-TEM) is 5.6 nm. X-ray photoelectron spectroscopy (XPS) signals confirm the chemical states of Fe, Zn, and O. A superconducting quantum interference device (SQUID) displays the magnetic response of ZFO NPs, showing a magnetic moment of 45.5 emu/gm at 70 kOe. These ZFO NPs were then employed for comparative cytotoxicity evaluation using MTT, crystal violet, and LDH assays on breast adenocarcinoma epithelial cell (MCF-7), triple-negative breast cancer lines (MDA-MB 231), and human embryonic kidney cell lines (HEK-293). Flow cytometric analysis of all the three cell lines were performed in various concentrations of ZFO NPs for automated cell counting and sorting based on live cells, cells entering in early or late apoptotic phase, as well as in the necrotic phase. This analysis confirmed that ZFO NPs are more cytotoxic towards triple-negative breast cancer cells (MDA-MB-231) as compared to breast adenocarcinoma cells (MCF-7) and normal cell lines (HEK-293), thus corroborating that ZFO can be exploited for cancer therapeutics.
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Adenocarcinoma , Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Violeta Genciana , Zinco , Células HEK293 , ApoptoseRESUMO
The negative impact on worldwide social well-being by the increasing rate of psychiatric diseases has led to a continuous new drug search. Even though the current therapeutic options exert their activity on multiple neurological targets, these have various adverse effects, causing treatment abandonment. Recent research has shown that Coriandrum sativum offers a rich source of metabolites, mainly terpenes and flavonoids, as useful agents against central nervous system disorders, with remarkable in vitro and in vivo activities on models related to these pathologies. Furthermore, studies have revealed that some compounds exhibit a chemical interaction with γ-aminobutyric acid, 5-hydroxytryptamine, and N-methyl-D-aspartate receptors, which are key components in the pathophysiology associated with psychiatric and neurological diseases. The current clinical evaluations of standardized extracts of C. sativum are scarce; however, one or more of its compounds represents an area of opportunity to test the efficacy of the plant as an anxiolytic, antidepressant, antiepileptic, or sleep enhancer. For this, the aim of the review was based on the pharmacological activities offered by the compounds identified and isolated from coriander and the processes involved in achieving their effect. In addition, lines of technological research, like molecular docking and nanoparticles, are proposed for the future development of phytomedicines, based on the bioactive molecules of C. sativum, for the treatment of psychiatric and neurological disorders addressed in the present study.
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Ansiolíticos , Coriandrum , Transtornos Mentais , Humanos , Coriandrum/química , Simulação de Acoplamento Molecular , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Transtornos Mentais/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismoRESUMO
Biopharmaceuticals are large, complex and labile therapeutic molecules prone to instability due to various factors during manufacturing. To ensure their safety, quality and efficacy, a wide range of critical quality attributes (CQAs) such as product concentration, aggregation, particle size, purity and turbidity have to be met. Size exclusion chromatography (SEC) is the gold standard to measure protein aggregation and degradation. However, other techniques such as dynamic light scattering (DLS) are employed in tandem to measure the particle size distribution (PSD) and polydispersity of biopharmaceutical formulations. In this study, the application of multi-angle dynamic light scattering (MADLS) was evaluated for the determination of particle size, particle concentration and aggregation in 3 different protein modalities, namely bovine serum albumin (BSA) and two biopharmaceuticals including a monoclonal antibody (mAb) and an enzyme. The obtained calibration curve (R2 > 0.95) for the particle number concentration of the 3 proteins and the observed correlation between MADLS and SEC (R2 = 0.9938) for the analysis of aggregation in the enzyme can be employed as a 3-in-1 approach to assessing particle size, concentration and aggregation for the screening and development of products while also reducing the number of samples and experiments required for analysis prior to other orthogonal tests.
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Produtos Biológicos , Difusão Dinâmica da Luz , Soroalbumina Bovina/química , Anticorpos Monoclonais/análise , LuzRESUMO
Background: Medical image segmentation is more complicated and demanding than ordinary image segmentation due to the density of medical pictures. A brain tumour is the most common cause of high mortality. Objectives: Extraction of tumorous cells is particularly difficult due to the differences between tumorous and non-tumorous cells. In ordinary convolutional neural networks, local background information is restricted. As a result, previous deep learning algorithms in medical imaging have struggled to detect anomalies in diverse cells. Methods: As a solution to this challenge, a deep convolutional generative adversarial network for tumour segmentation from brain Magnetic resonance Imaging (MRI) images is proposed. A generator and a discriminator are the two networks that make up the proposed model. This network focuses on tumour localisation, noise-related issues, and social class disparities. Results: Dice Score Coefficient (DSC), Peak Signal to Noise Ratio (PSNR), and Structural Index Similarity (SSIM) are all generally 0.894, 62.084 dB, and 0.88912, respectively. The model's accuracy has improved to 97 percent, and its loss has reduced to 0.012. Conclusions: Experiments reveal that the proposed approach may successfully segment tumorous and benign tissues. As a result, a novel brain tumour segmentation approach has been created.