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1.
Development ; 149(4)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35029672

RESUMO

The submergence-induced hypoxic condition negatively affects the plant growth and development, and causes early onset of senescence. Hypoxia alters the expression of a number of microRNAs (miRNAs). However, the molecular function of submergence stress-induced miRNAs in physiological or developmental changes and recovery remains poorly understood. Here, we show that miR775 is an Arabidopsis thaliana-specific young and unique miRNA that possibly evolved non-canonically. miR775 post-transcriptionally regulates GALACTOSYLTRANSFERASE 9 (GALT9) and their expression is inversely affected at 24 h of complete submergence stress. The overexpression of miR775 (miR775-Oe) confers enhanced recovery from submergence stress and reduced accumulation of RBOHD and ROS, in contrast to wild-type and MIM775 Arabidopsis shoot. A similar recovery phenotype in the galt9 mutant indicates the role of the miR775-GALT9 module in post-submergence recovery. We predicted that Golgi-localized GALT9 is potentially involved in protein glycosylation. The altered expression of senescence-associated genes (SAG12, SAG29 and ORE1), ethylene signalling (EIN2 and EIN3) and abscisic acid (ABA) biosynthesis (NCED3) pathway genes occurs in miR775-Oe, galt9 and MIM775 plants. Thus, our results indicate the role for the miR775-GALT9 module in post-submergence recovery through a crosstalk between the ethylene signalling and ABA biosynthesis pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Etilenos/farmacologia , Galactosiltransferases/metabolismo , MicroRNAs/metabolismo , Senescência Vegetal/efeitos dos fármacos , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Sítios de Ligação , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Dioxigenases/genética , Dioxigenases/metabolismo , Galactosiltransferases/genética , Complexo de Golgi/metabolismo , MicroRNAs/química , MicroRNAs/genética , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/genética , Estresse Fisiológico
2.
J Sci Food Agric ; 104(10): 5675-5688, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38285130

RESUMO

Nanotechnology is a rapidly developing discipline that has the potential to transform the way we approach problems in a variety of fields, including agriculture. The use of nanotechnology in sustainable agriculture has gained popularity in recent years. It has various applications in agriculture, such as the development of nanoscale materials and devices to boost agricultural productivity, enhance food quality and safety, improve the efficiency of water and nutrient usage, and reduce environmental pollution. Nanotechnology has proven to be very beneficial in this field, particularly in the development of nanoscale delivery systems for agrochemicals such as pesticides, fertilizers, and growth regulators. These nanoscale delivery technologies offer various benefits over conventional delivery systems, including better penetration and distribution, enhanced efficacy, and lower environmental impact. Encapsulating agrochemicals in nanoscale particles enables direct delivery to the targeted site in the plant, thereby reducing waste and minimizing off-target effects. Plants are fundamental building blocks of all ecosystems and evaluating the interaction between nanoparticles (NPs) and plants is a crucial aspect of risk assessment. This critical review therefore aims to provide an overview of the latest advances regarding the positive and negative effects of nanotechnology in agriculture. It also explores potential future research directions focused on ensuring the safe utilization of NPs in this field, which could lead to sustainable development. © 2024 Society of Chemical Industry.


Assuntos
Agricultura , Nanotecnologia , Agroquímicos/química , Agroquímicos/efeitos adversos , Produtos Agrícolas/crescimento & desenvolvimento , Fertilizantes/análise , Nanopartículas/química , Nanotecnologia/métodos , Praguicidas/química , Desenvolvimento Sustentável
3.
J Assoc Physicians India ; 72(8): 107-108, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39163083

RESUMO

We present a case of a 56-year-old female with rheumatoid arthritis (RA) who has been on methotrexate for 9 years and has been complaining of high-grade fever for the past 1 month with no localizing signs and symptoms. She was thoroughly evaluated before being labeled as pyrexia of unknown origin. Histoplasmosis was suspected after bone marrow aspiration smear examination. The presence of histoplasma antigen in the urine confirmed our diagnosis. Fever responded after 2 weeks of liposomal amphotericin B and patient discharged in stable condition on tablet itraconazole.


Assuntos
Anfotericina B , Artrite Reumatoide , Febre de Causa Desconhecida , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/complicações , Histoplasmose/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Feminino , Pessoa de Meia-Idade , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/diagnóstico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Histoplasma/isolamento & purificação , Itraconazol/uso terapêutico
4.
Physiol Plant ; 175(4): e13968, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37402164

RESUMO

Serotonin is a well-studied pineal hormone that functions as a neurotransmitter in mammals and is found in varying amounts in diverse plant species. By modulating gene and phytohormonal crosstalk, serotonin has a significant role in plant growth and stress response, including root, shoot, flowering, morphogenesis, and adaptability responses to numerous environmental signals. Despite its prevalence and importance in plant growth and development, its molecular action, regulation and signalling processes remain unknown. Here, we highlight the current knowledge of the role of serotonin-mediated regulation of plant growth and stress response. We focus on serotonin and its regulatory connections with phytohormonal crosstalk and address their possible functions in coordinating diverse phytohormonal responses during distinct developmental phases, correlating with melatonin. Additionally, we have also discussed the possible role of microRNAs (miRNAs) in the regulation of serotonin biosynthesis. In summary, serotonin may act as a node molecule to coordinate the balance between plant growth and stress response, which may shed light on finding its key regulatory pathways for uncovering its mysterious molecular network.


Assuntos
Melatonina , Serotonina , Serotonina/metabolismo , Desenvolvimento Vegetal , Reguladores de Crescimento de Plantas/metabolismo , Plantas/genética , Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
5.
Org Biomol Chem ; 21(38): 7691-7695, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37691458

RESUMO

Maximum confusion in porphyrinoids can be achieved by inter-linking heterocycles only through 2,4-connectivity. 20π confused porphycene and 30π expanded porphycene represent examples with the highest number of confused heterocyclic units in a given macrocycle. They significantly differ from the parent 20π porphycene and 30π hexaphyrin in their structural, electronic and redox properties due to the cross conjugation arising from the 2,4-connectivity of the heterocycle. They have been characterized by single crystal X-ray diffraction studies and their aromatic features have been substantiated by quantum chemical calculations.

6.
J Chem Phys ; 158(7): 074906, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36813706

RESUMO

We report the synthesis and experimental studies on the liquid crystalline phase of a homologous series of compounds comprised of strongly asymmetric bent-core banana shaped molecules. Our x-ray diffraction studies clearly indicate that the compounds exhibit a frustrated tilted smectic phase with layer undulated structure. The low value of the dielectric constant as well as switching current measurements indicate the absence of polarization in this layer undulated phase. In spite of the absence of polarization, a planar aligned sample can be transformed irreversibly to a higher birefringent texture on the application of a high electric field. The zero field texture can only be retrieved by heating the sample to the isotropic phase and cooling it subsequently to the mesophase. We propose a double tilted smectic structure having layer undulation to account for the experimental observations with the layer undulation arising due to the leaning of the molecules in the layer.

7.
Plant Cell Rep ; 42(3): 649-653, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36680640

RESUMO

KEY MESSAGE: We highlight the newly emerged regulatory role of a mitotic kinase AUR1, its activator, and its microtubule-associated proteins (MAPs) in infection thread formation for root nodule symbiosis.


Assuntos
Fabaceae , Rhizobium , Fabaceae/metabolismo , Fixação de Nitrogênio , Nódulos Radiculares de Plantas/metabolismo , Verduras , Simbiose
8.
Physiol Plant ; 174(4): e13736, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35716004

RESUMO

Deepwater is an abiotic stress that limits rice cultivation worldwide due to recurrent floods. The miRNAs and lncRNAs are two non-coding RNAs emerging as major regulators of gene expressions under different abiotic stresses. However, the regulation of these two non-coding RNAs under deepwater stress in rice is still unexplored. In this study, small RNA-seq and RNA-seq from internode and node tissues were analyzed to predict deepwater stress responsive miRNAs and lncRNAs, respectively. Additionally, a competitive endogenous RNA (ceRNA) study revealed about 69 and 25 lncRNAs acting as endogenous target mimics (eTM) with the internode and node miRNAs, respectively. In ceRNA analyses, some of the key miRNAs such as miR1850.1, miR1848, and IN-nov-miR145 were upregulated while miR159e was downregulated, and their respective eTM lncRNAs and targets were found to have opposite expressions. Moreover, we have transiently expressed one module (IN-nov-miR145-Cc-TCONS_00011544-Os11g36430.3) in tobacco leaves. The integrated analysis has identified differentially expressed (DE) miRNAs, lncRNAs and their target genes, and the complex regulatory network, which might lead to stem elongation under deepwater stress. In this novel attempt to identify and characterize miRNAs and lncRNAs under deepwater stress in rice, we have provided, probably for the first time, a reference platform to study the interactions of these two non-coding RNAs with respective target genes through transient expression analyses.


Assuntos
MicroRNAs , Oryza , RNA Longo não Codificante , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Oryza/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Estresse Fisiológico/genética
9.
Comput Electr Eng ; 101: 108028, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35498557

RESUMO

The concept of fuzzy set, intuitionistic set, and mediative fuzzy set as a generalization of a crisp set have been introduced in many real-life applications. The concept of crisp relation between elements of sets can be extended to fuzzy relations. Extended relations will be considered as relations on fuzzy sets. In this work, we developed the concept of mediative fuzzy relation and meditative fuzzy projection in the context of fuzzy relation and fuzzy projection. We extended the basic operations of fuzzy projection into intuitionistic fuzzy projection and then in the mediative fuzzy projection. We have shown the credibility and impact of mediative index factor involves in the mediative fuzzy projection in context of prediction work in relation to the proposed model. Further, we applied the mediative fuzzy projection in the medical diagnosis in post-COVID-19 patients. The obtained results have also been discussed with their geometrical representation.

10.
Appl Soft Comput ; 105: 107285, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33723486

RESUMO

This paper presents a model based on mediative fuzzy logic in this COVID-19 pandemic. COVID-19 (novel coronavirus respiratory disease) has become a pandemic now and the whole world has been affected by this disease. Different methodologies and many prediction techniques based on various models have been developed so far. In the present article, we have developed a mediative fuzzy correlation technique based on the parameters for COVID-19 patients from different parts of India. The proposed mediative fuzzy correlation technique provides the relation between the increments of COVID-19 positive patients in terms of the passage of increment with respect to time. The peaks of infected cases in connection with the other condition are estimated from the available data. The mediative fuzzy logic mathematical model can be utilized to find a good fit or a contradictory model for any pandemic model. The proposed approach to the prediction in COVID-19 based on mediative fuzzy logic has produced promising results for the continuous contradictory prediction in India.

11.
Carcinogenesis ; 40(10): 1179-1190, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31219154

RESUMO

In pre-clinical models, co-existence of Human Epidermal Growth Factor Receptor-2 (HER2)-amplification and PI3K catalytic subunit (PIK3CA) mutations results in aggressive, anti-HER2 therapy-resistant breast tumors. This is not always reflected in clinical setting. We speculated that the complex interaction between the HER2 and PIK3CA oncogenes is responsible for such inconsistency. We performed series of biochemical, molecular and cellular assays on genetically engineered isogenic mammary epithelial cell lines and breast cancer cells expressing both oncogenes. In vitro observations were validated in xenografts models. We showed that H1047R, one of the most common PIK3CA mutations, is responsible for endowing a senescence-like state in mammary epithelial cells overexpressing HER2. Instead of imposing a permanent growth arrest characteristic of oncogene-induced senescence, the proteome secreted by the mutant cells promotes stem cell enrichment, angiogenesis, epithelial-to-mesenchymal transition, altered immune surveillance and acute vulnerability toward HSP90 inhibition. We inferred that the pleiotropism, as observed here, conferred by the mutated oncogene, depending on the host microenvironment, contributes to conflicting pre-clinical and clinical characteristics of HER2+, mutated PIK3CA-bearing tumor cells. We also came up with a plausible model for evolution of breast tumors from mammary epithelial cells harboring these two molecular lesions.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Senescência Celular , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Mutação , Receptor ErbB-2/metabolismo , Animais , Apoptose , Mama/metabolismo , Neoplasias da Mama/metabolismo , Proliferação de Células , Células Cultivadas , Classe I de Fosfatidilinositol 3-Quinases/genética , Transição Epitelial-Mesenquimal , Feminino , Proteínas de Choque Térmico HSP90/genética , Humanos , Camundongos , Camundongos Nus , Receptor ErbB-2/genética
13.
Planta ; 248(3): 545-558, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29968061

RESUMO

MAIN CONCLUSION: Present review addresses the advances made in the understanding of biogenesis of plant small RNAs and their role in plant development. We discuss the elaborate role of microRNAs (miRNAs) and trans-acting small interfering RNAs (ta-siRNAs) in various aspects of plant growth and development and highlight relevance of small RNA mobility. Small non-coding RNAs regulate various aspects of plant development. Small RNAs (sRNAs) of 21-24 nucleotide length are derived from double-stranded RNAs through the combined activity of several biogenesis and processing components. These sRNAs function by negatively regulating the expression of target genes. miRNAs and ta-siRNAs constitute two important classes of endogenous small RNAs in plants, which play important roles in plant growth and developmental processes like embryogenesis, organ formation and patterning, shoot and root growth, and reproductive development. Biogenesis of miRNAs is a multistep process which includes transcription, processing and modification, and their loading onto RNA-induced silencing complex (RISC). RISC-loaded miRNAs carry out post-transcriptional silencing of their target(s). Recent studies identified orthologues of different biogenesis components of novel and conserved small RNAs from different model plants. Although many small RNAs have been identified from diverse plant species, only a handful of them have been functionally characterized. In this review, we discuss the advances made in understanding the biogenesis, functional conservation/divergence in miRNA-mediated gene regulation, and the developmental role of small RNAs in different plant species.


Assuntos
Desenvolvimento Vegetal , RNA de Plantas/metabolismo , Pequeno RNA não Traduzido/metabolismo , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Germinação , Meristema/crescimento & desenvolvimento , Desenvolvimento Vegetal/genética , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/crescimento & desenvolvimento , Plantas/genética , Plantas/metabolismo , Sementes/crescimento & desenvolvimento
15.
Trends Plant Sci ; 29(6): 610-612, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38102044

RESUMO

In the intricate landscape of cellular function, proper protein folding is pivotal for cellular processes, particularly within the endoplasmic reticulum (ER). In a recent study, Ko et al. reveal a signaling role for inositol-requiring enzyme 1 (IRE1) in ER stress and identify PHOSPHATASE TYPE 2CA (PP2CA)-INTERACTING RING FINGER PROTEIN 1 (PIR1) as a crucial plant-specific regulator, balancing the unfolded protein response (UPR) and ubiquitin-proteasome system (UPS) by modulating ABI5 stability, unveiling intricate stress response connections.


Assuntos
Estresse do Retículo Endoplasmático , Complexo de Endopeptidases do Proteassoma , Transdução de Sinais , Resposta a Proteínas não Dobradas , Complexo de Endopeptidases do Proteassoma/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Retículo Endoplasmático/metabolismo
16.
Phys Rev E ; 109(2-1): 024703, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38491713

RESUMO

We report experimental investigations of a liquid crystal comprising thiophene-based achiral bent-core banana shaped molecules. The compound exhibits the following phase sequence on cooling: Isotropic (517.4 K), N (514.9 K), de Vries SmA (402 K), SmC. Practically no layer contraction was observed across the SmA to SmC transition, confirming the "de Vries" nature of the SmA phase. Interestingly, the crystallization does not occur on cooling the sample, unlike most other liquid crystals. Instead, the SmC phase undergoes a glass transition at 271 K even at a slow cooling rate. The dielectric spectroscopy studies carried out on the sample reveal the presence of a dielectric mode whose relaxation process is of the Cole-Cole type. The relaxation frequency of the mode was found to drop rapidly with decreasing temperature, confirming the glassy behavior. The variation of relaxation frequency with temperature follows the Vogel-Fulcher-Tammann equation, indicating the fragile glassy nature of the sample. This report identifies a bent-core liquid crystal exhibiting a "de Vries" SmA phase and glassy behavior at lower temperatures.

17.
Nat Genet ; 35(1): 84-9, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12923531

RESUMO

Hermansky-Pudlak syndrome (HPS; MIM 203300) is a genetically heterogeneous disorder characterized by oculocutaneous albinism, prolonged bleeding and pulmonary fibrosis due to abnormal vesicle trafficking to lysosomes and related organelles, such as melanosomes and platelet dense granules. In mice, at least 16 loci are associated with HPS, including sandy (sdy; ref. 7). Here we show that the sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1 (encoding dysbindin) and that mutation of the human ortholog DTNBP1 causes a novel form of HPS called HPS-7. Dysbindin is a ubiquitously expressed protein that binds to alpha- and beta-dystrobrevins, components of the dystrophin-associated protein complex (DPC) in both muscle and nonmuscle cells. We also show that dysbindin is a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1; refs. 9-11), which regulates trafficking to lysosome-related organelles and includes the proteins pallidin, muted and cappuccino, which are associated with HPS in mice. These findings show that BLOC-1 is important in producing the HPS phenotype in humans, indicate that dysbindin has a role in the biogenesis of lysosome-related organelles and identify unexpected interactions between components of DPC and BLOC-1.


Assuntos
Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas Associadas à Distrofina , Síndrome de Hermanski-Pudlak/genética , Mutação , Animais , Células COS , Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Disbindina , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Lectinas , Substâncias Macromoleculares , Masculino , Melanossomas/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Transgênicos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fosfoproteínas/metabolismo , Ligação Proteica
18.
Org Lett ; 25(36): 6628-6632, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37669470

RESUMO

Thiophene-based expanded porphyrinoids undergo a transition from a planar conformation to a twisted conformation upon a systematic increase in the number of thiophene units. Octaphyrin, with 40π electrons, displayed temperature-dependent interconversion between planar and nonplanar conformations in the solution state, in contrast to the rigid planar conformation in the solid state. 60π-dodecaphyrin and 70π-tetradecaphyrin have the maximum number of π-electrons for 12- and 14-heterocycle porphyrinoids, respectively. Spectro-electrochemical measurements confirmed facile reversible two-electron oxidation and the unstable radical cation intermediate in these systems.

19.
ISA Trans ; 124: 124-134, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33500125

RESUMO

In this paper, we have considered a mathematical model that deals with the effectiveness of the measures that may be helpful for reducing the spread of the COVID-19 virus in the society. Here we have illustrated the importance of lock down in controlling and maintaining the spread of the COVID-19 virus. The impact of the virus on the susceptible population has been considered in the model. Also, we have taken into account the susceptible population, which by taking preventive measures viz., by having strong immunity, maintaining social distancing, wearing PPE kits and masks etc., is able to reduce the possibility of getting infected from the virus. Local as well as global stability of the equilibrium points of the model have been studied using Lyapunov function and the geometrical approach techniques. Basic reproduction number has also been obtained by using the next generation matrix. To show the effectiveness of the model, different cases obtained by varying the parameters involved in the model have been considered. A comparison between the actual number of infected cases in India and that obtained by the proposed model, showing the effectiveness of the proposed model, has also been carried out.


Assuntos
COVID-19 , Número Básico de Reprodução , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Humanos , Modelos Teóricos , SARS-CoV-2
20.
Front Oncol ; 12: 953098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052261

RESUMO

Glioblastoma multiforme (GBM) is known as the primary malignant and most devastating form of tumor found in the central nervous system of the adult population. The active pharmaceutical component in current chemotherapy regimens is mostly hydrophobic and poorly water-soluble, which hampers clinical implications. Nanodrug formulations using nanocarriers loaded with such drugs assisted in water dispersibility, improved cellular permeability, and drug efficacy at a low dose, thus adding to the overall practical value. Here, we successfully developed a water-dispersible and biocompatible nanocargo (GO-PEG) based on covalently modified graphene oxide (GO) with a 6-armed poly(ethylene glycol) amine dendrimer for effective loading of the two hydrophobic anticancer drug molecules, CPI444 and vatalanib. These drug molecules target adenosine receptor (A2AR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and type III stem cell receptor tyrosine kinase (c-KIT), which plays a crucial role in cancers. The effective cellular delivery of the drugs when loaded on GO-PEG is attributed to the increased permeability of the drug-nanoconjugate formulation. We observed that this combinatorial drug treatment with nanocargo resulted in a significant reduction in the overall cell survival as supported by reduced calcium levels and stem cell markers such as Oct4 and Nanog, which are two of the prime factors for GBM stem cell proliferation. Furthermore, reduced expression of CD24 upon treatment with nanoformulation impeded cellular migration. Cellular assays confirmed inhibition of cell proliferation, migration, and angiogenic potential of GBM treated with GO-PEG-Drug conjugates. Ultimately, GBM U87 cells assumed programmed cell death at a very low concentration due to nanocarrier-mediated drug delivery along with the chosen combination of drugs. Together, this study demonstrated the advantage of GO-PEG mediated combined delivery of CPI444 and vatalanib drugs with increased permeability, a three-pronged combinatorial strategy toward effective GBM treatment.

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