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1.
Carbohydr Polym ; 342: 122267, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39048183

RESUMO

This article explores the use of carrageenan-based biomaterials in developing sustainable and efficient intelligent food packaging solutions. The research in this field has seen a notable surge, evident from >1000 entries in databases such as Web of Science, PubMed and Science Direct between 2018 and 2023. Various film preparation techniques are explored, including solvent casting, layer-by-layer (LbL) assembly, and electrospinning. Solvent casting is commonly used to incorporate active compounds, while LbL assembly and electrospinning are favored for enhancing mechanical properties and solubility. Carrageenan's film-forming characteristics enable the production of transparent films, ideal for indicator films that facilitate visual inspection for color changes indicative of pH variations, crucial for detecting food spoilage. Surface properties can be modified using additives like plant extracts to regulate moisture interaction, affecting shelf life and food safety. These materials' antioxidant and antimicrobial attributes are highlighted, demonstrating their efficacy against pathogens such as E. coli.


Assuntos
Materiais Biocompatíveis , Carragenina , Embalagem de Alimentos , Embalagem de Alimentos/métodos , Carragenina/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Escherichia coli/efeitos dos fármacos , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Solubilidade , Antibacterianos/farmacologia , Antibacterianos/química
2.
J Am Chem Soc ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058407

RESUMO

The ability to correlate the structure of a molecule with its properties is the key to the rational and accelerated design of new functional compounds and materials. Taking photoswitches as an example, the thermal stability of the metastable state is a crucial property that dictates their application in molecular systems. Indigos have recently emerged as an attractive motif for designing photoswitchable molecules due to their red-light addressability, which can be advantageous in biomedical and material applications. The lack of synthetic techniques to derivatize the abundant parent dye and a thorough understanding of the impact of structural factors on the photochemical and thermal properties hinder broad applications of this emerging photoswitch class. Herein, we report an efficient copper-catalyzed indigo N-arylation that enables the installation of a wide variety of aryl moieties carrying useful functional groups. The exclusive selectivity for monoarylation likely originates from a bimetallic cooperative mechanism through a binuclear copper-indigo intermediate. Functional N-aryl-N'-alkylindigos were prepared and shown to photoisomerize efficiently under red light. Moreover, this design allows for the modulation of thermal half-lives through N-aryl substituents, while the N'-alkyl groups enable the independent attachment of functional moieties without affecting the photochromic properties. A strong correlation between the structure of the N-aryl moiety and the thermal stability of the photogenerated Z-isomers was achieved by multivariate linear regression models obtained through a data-science workflow. This work thus builds an avenue leading to versatile red-light photoswitches and a general method for structure-property correlation that is expected to be broadly applicable to the design of photoresponsive molecules.

3.
Front Microbiol ; 15: 1406904, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939182

RESUMO

This review aims to comprehensively chronicle the biosynthesis, classification, properties, and applications of bacteriocins produced by Weissella genus strains, particularly emphasizing their potential benefits in food preservation, human health, and animal productivity. Lactic Acid Bacteria (LAB) are a class of microorganisms well-known for their beneficial role in food fermentation, probiotics, and human health. A notable property of LAB is that they can synthesize antimicrobial peptides known as bacteriocins that exhibit antimicrobial action against both closely related and other bacteria as well. Bacteriocins produced by Weissella spp. are known to exhibit antimicrobial activity against several pathogenic bacteria including food spoilage species, making them highly invaluable for potential application in food preservation and food safety. Importantly, they provide significant health benefits to humans, including combating infections, reducing inflammation, and modulating the gut microbiota. In addition to their applications in food fermentation and probiotics, Weissella bacteriocins show promising prospects in poultry production, processing, and improving animal productivity. Future research should explore the utilization of Weissella bacteriocins in innovative food safety measures and medical applications, emphasizing their potential to combat antibiotic-resistant pathogens, enhance gut microbiota composition and function, and synergize with existing antimicrobial therapies.

4.
Sci Rep ; 14(1): 10992, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744854

RESUMO

The present study introduces "rock slope instability score (RSIS)" a novel classification system for assessing rock slope stability. It takes into account geological and geotechnical parameters, as well as the impact of human activities and triggering parameters, which have become more frequent due to climate change and few of them have been ignored in existing classifications. The study focuses on rock slopes of various lithologies from the Indian Himalayas. The development of this new classification system is based on the examination of 81 different rock slopes from various states of the Indian Himalayas. Extensive field surveys, rock sampling, geotechnical laboratory tests, and ground measurements have been conducted at the various slope sites to establish a comprehensive scoring system for the stability assessment. The distributions of weightage to each parameter have been considered, corresponding to its degree of impact in causing slope instability. Sensitivity analysis of all defined parameters of RSIS system has revealed that the majority of the parameters exhibit a strong positive correlation, with Pearson correlation coefficients ranging from 0.74 to 0.61. However, two parameters, namely discontinuity dip and the relationship between slope & discontinuity direction, gives moderate relationship with correlation coefficient values of 0.48 and 0.41, respectively. To avoid any designer biasness in the system, several individuals gathered data set at different times. The proposed classification system has demonstrated a strong correlation with the actual slope condition, and it is quite promising. The outcome of RSIS classification for studied 81 slopes classified 2 slopes under stable condition, 21 slopes as partially stable, 44 as unstable, and 14 as completely unstable.

5.
ACS Appl Bio Mater ; 7(6): 3701-3713, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38748449

RESUMO

Metal-organic complexes have shown astounding bioactive properties; however, they are rarely explored as biomaterials. Recent studies showed that carboxymethyl-chitosan (CMC) genipin-conjugated zinc biomimetic scaffolds have unique bioselective properties. The biomaterial was reported to be mammalian cell-friendly; at the same time, it was found to discourage microbial biofilm formation on its surface, which seemed to be a promising solution to addressing the problem of trauma-associated biofilm formation and development of antimicrobial resistance. However, the mechanically frail characteristics and zinc overload raise concerns and limit the potential of the said biomaterials. Hence, the present work is focused on improving the strength of the earlier scaffold formulations, testing its in vivo efficacy and reaffirming its action against biofilm-forming microbe Staphylococcus aureus. Scaling up of CMC proportion increased rigidity, and 8% CMC was found to be the ideal concentration for robust scaffold fabrication. Freeze-dried CMC scaffolds with or without genipin (GP) cross-linking were conjugated with zinc using 2 M zinc acetate solution. Characterization results indicated that the CMC-Zn scaffolds, without genipin, showed mechanical properties close to bone fillers, resist in vitro enzymatic degradation until 4 weeks, are porous in nature, and have radiopacity close to mandibular bones. Upon implantation in a subcutaneous pocket of Wistar rats, the scaffolds showed tissue in-growth with simultaneous degradation without any signs of toxicity past 28 days. Neither were there any signs of toxicity in any of the vital organs. Considering many superior properties among the other formulations, the CMC-Zn scaffolds were furthered for biofilm studies. CMC-Zn showed negligible S. aureus biofilm formation on its surface as revealed by an alamar blue-based study. RT-PCR analysis revealed that CMC-Zn downregulated the expression of pro-biofilm effector genes such as icaC and clfB. A protein docking study predicted the inhibitory mechanism of CMC-Zn. Although it binds strongly when alone, at high density, it may cause inactivation of the transmembrane upstream activators of the said genes, thereby preventing their dimerization and subsequent inactivation of the effector genes. In conclusion, zinc-conjugated carboxymethyl-chitosan scaffolds are mechanically robust, porous, yet biodegradable, harmless to the host in the long term, they are radiopaque and prevent biofilm gene expression in notorious microbes; hence, they could be a suitable candidate for bone filler applications.


Assuntos
Materiais Biocompatíveis , Biofilmes , Teste de Materiais , Staphylococcus aureus , Zinco , Biofilmes/efeitos dos fármacos , Zinco/química , Zinco/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Animais , Porosidade , Ratos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Tamanho da Partícula , Quitosana/química , Quitosana/farmacologia , Testes de Sensibilidade Microbiana , Alicerces Teciduais/química
6.
Curr Res Food Sci ; 8: 100720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559379

RESUMO

In the evolving landscape of food packaging, lipid-based edible films and coatings are emerging as a sustainable and effective solution for enhancing food quality and prolonging shelf life. This critical review aims to offer a comprehensive overview of the functional properties, roles, and fabrication techniques associated with lipid-based materials in food packaging. It explores the unique advantages of lipids, including waxes, resins, and fatty acids, in providing effective water vapor, gas, and microbial barriers. When integrated with other biopolymers, such as proteins and polysaccharides, lipid-based composite films demonstrate superior thermal, mechanical, and barrier properties. The review also covers the application of these innovative coatings in preserving a wide range of fruits and vegetables, highlighting their role in reducing moisture loss, controlling respiration rates, and maintaining firmness. Furthermore, the safety aspects of lipid-based coatings are discussed to address consumer and regulatory concerns.

7.
RSC Chem Biol ; 5(3): 249-261, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38456040

RESUMO

Intracellular protein delivery shows promise as a selective and specific approach to cancer therapy. However, a major challenge is posed by delivering proteins into the target cells. Despite the development of nanoparticle (NP)-based approaches, a versatile and biocompatible delivery system that can deliver active therapeutic cargo into the cytosol while escaping endosome degradation remains elusive. In order to overcome these challenges, a polymeric nanocarrier was prepared using cationic dextrin (CD), a biocompatible and biodegradable polymer, to encapsulate and deliver cytochrome C (Cyt C), a therapeutic protein. The challenge of endosomal escape of the nanoparticles was addressed by co-delivering the synthesized NP construct with chloroquine, which enhances the endosomal escape of the therapeutic protein. No toxicity was observed for both CD NPs and chloroquine at the concentration tested in this study. Spectroscopic investigations confirmed that the delivered protein, Cyt C, was structurally and functionally active. Additionally, the delivered Cyt C was able to induce apoptosis by causing depolarization of the mitochondrial membrane in HeLa cells, as evidenced by flow cytometry and microscopic observations. Our findings demonstrate that an engineered delivery system using CD NPs is a promising platform in nanomedicine for protein delivery applications.

8.
ACS Biomater Sci Eng ; 10(4): 2510-2522, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38466622

RESUMO

Theranostic systems, which integrate therapy and diagnosis into a single platform, have gained significant attention as a promising approach for noninvasive cancer treatment. The field of image-guided therapy has revolutionized real-time tumor detection, and within this domain, plasmonic nanostructures have garnered significant attention. These structures possess unique localized surface plasmon resonance (LSPR), allowing for enhanced absorption in the near-infrared (NIR) range. By leveraging the heat generated from plasmonic nanoparticles upon NIR irradiation, target cancer cells can be effectively eradicated. This study introduces a plasmonic gold dogbone-nanorattle (AuDB NRT) structure that exhibits broad absorption in the NIR region and demonstrates a photothermal conversion efficiency of 35.29%. When exposed to an NIR laser, the AuDB NRTs generate heat, achieving a maximum temperature rise of 38 °C at a concentration of 200 µg/mL and a laser power density of 3 W/cm2. Additionally, the AuDB NRTs possess intrinsic electromagnetic hotspots that amplify the signal of a Raman reporter molecule, making them an excellent probe for surface-enhanced Raman scattering-based bioimaging of cancer cells. To improve the biocompatibility of the nanorattles, the AuDB NRTs were conjugated with mPEG-thiol and successfully encapsulated into cationic dextrin nanoparticles (CD NPs). Biocompatibility tests were performed on HEK 293 A and MCF-7 cell lines, revealing high cell viability when exposed to AuDB NRT-CD NPs. Remarkably, even at a low laser power density of 1 W/cm2, the application of the NIR laser resulted in a remarkable 80% cell death in cells treated with a nanocomposite concentration of 100 µg/mL. Further investigation elucidated that the cell death induced by photothermal heat followed an apoptotic mechanism. Overall, our findings highlight the significant potential of the prepared nanocomposite for cancer theranostics, combining effective photothermal therapy along with the ability to image cancer cells.


Assuntos
Nanocompostos , Nanopartículas , Neoplasias , Humanos , Ouro/farmacologia , Ouro/química , Dextrinas , Nanomedicina Teranóstica/métodos , Células HEK293 , Nanopartículas/uso terapêutico , Neoplasias/terapia
9.
Sci Total Environ ; 921: 171051, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382616

RESUMO

Glyphosate (Gly) is a massively utilized toxic herbicide exceeding its statutory restrictions, causing adverse environmental and health impacts. Engineered nanomaterials, even though are integral to remediate Gly, their practical use is limited due to time and energy driven purifications, and negative environmental impacts. Here, a 3D wide area (~1.6 ± 0.4 cm2) Cu2O nanoparticle supported biotemplate is designed using fish-scale wastes as a sustainable approach for the ultra-efficient and selective hand-remediation of Gly from real-time samples from agro-farms. While the innate metal binding and reducing ability of collagenous scales aided self-synthesis cum grafting of Cu2O, the selective binding potential of Cu2O to Gly facilitated its hand-retrieval; as assessed using optical characterizations, Fourier transform infrared spectroscopy, thermogravimetric analysis and liquid chromatography mass spectrometry. Optimization studies revealed extractions of diverse pay-loads of Gly between 0.1 µg/mL to 40 µg/mL per 80 mg biotemplate grafted with ~6.354 µg of sub-5 nm Cu2O and was exponential to the number of Cu2O@biotemplates. Even though pH and surfactant didn't have any impact on the adsorption of Gly to the Cu2O@biotemplates, increase in the ionic strength led to a drastic increase in the adsorption. Density function theory simulations unveiled the involvement of phosphonic and carboxylic groups of Gly for interaction with Cu2O with a bond length of 1.826 Å and 1.833 Å, respectively. Overall, our sustainably generated, cost-efficient, hand-retrievable Cu2O supported biotemplate can be generalized to extract diverse organophosphorus toxins from agro-farms and other sewage embodiments. SYNOPSIS: Glyphosate is an excessively applied herbicide with potent health hazards and carcinogenicity. Thus, a hand removable Cu2O-supported biotemplate to selectively and efficiently remediate glyphosate from irrigation water is developed.


Assuntos
Glifosato , Herbicidas , Animais , Herbicidas/química , Água , Tensoativos , Bioengenharia
10.
RNA Biol ; 21(1): 1-14, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38329136

RESUMO

In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.


Assuntos
Neoplasias Hematológicas , Leucemia , Humanos , Regulação da Expressão Gênica , RNA/genética , Neoplasias Hematológicas/genética , Leucemia/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
11.
Foods ; 13(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338521

RESUMO

Entomophagy describes the practice of eating insects. Insects are considered extremely nutritious in many countries worldwide. However, there is a lethargic uptake of this practice in Europe where consuming insects and insect-based foodstuffs is often regarded with disgust. Such perceptions and concerns are often due to a lack of exposure to and availability of food-grade insects as a food source and are often driven by neophobia and cultural norms. In recent years, due to accelerating climate change, an urgency to develop alternate safe and sustainable food-sources has emerged. There are currently over 2000 species of insects approved by the World Health Organization as safe to eat and suitable for human consumption. This review article provides an updated overview of the potential of edible insects as a safe, palatable, and sustainable food source. Furthermore, legislation, food safety issues, and the nutritional composition of invertebrates including, but not limited, to crickets (Orthoptera) and mealworms (Coleoptera) are also explored within this review. This article also discusses insect farming methods and the potential upscaling of the industry with regard to future prospects for insects as a sustainable food source. Finally, the topics addressed in this article are areas of potential concern to current and future consumers of edible insects.

12.
J Biomed Mater Res B Appl Biomater ; 112(3): e35384, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38400798

RESUMO

This study aims at developing a calcium magnesium phosphate-based bone biocement that combines a natural polymer and regenerative properties of bone bonding materials. The formulation of this biocement consists of oxidized guar gum, polydopamine, and calcium magnesium phosphate. The oxidized guar gum is easily soluble in water and has a slightly basic pH, unlike unmodified guar gum, thus allowing a homogenous paste to form in the alkaline environment of calcium magnesium phosphate. Three different oxidized degrees of guar gum were made, and the impact on the biocement properties was studied. The modified guar gum-reinforced biocement (OGG C2) displayed higher mechanical strength and lower degradation rates than OGG B1 and OGG A0. Furthermore, samples with polydopamine exhibited better results, thus, improving the already reinforced biocement. Morphological studies of the biocement displayed a highly porous structure with porosity varying among biocement containing different oxidized guar gum and polydopamine levels.


Assuntos
Galactanos , Fosfatos , Gomas Vegetais , Galactanos/química , Mananas/química
13.
Blood Adv ; 8(2): 261-275, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38048400

RESUMO

ABSTRACT: RNA-binding proteins (RBPs) are emerging as a novel class of therapeutic targets in cancer, including in leukemia, given their important role in posttranscriptional gene regulation, and have the unexplored potential to be combined with existing therapies. The RBP insulin-like growth factor 2 messenger RNA-binding protein 3 (IGF2BP3) has been found to be a critical regulator of MLL-AF4 leukemogenesis and represents a promising therapeutic target. Here, we study the combined effects of targeting IGF2BP3 and menin-MLL interaction in MLL-AF4-driven leukemia in vitro and in vivo, using genetic inhibition with CRISPR-Cas9-mediated deletion of Igf2bp3 and pharmacologic inhibition of the menin-MLL interaction with multiple commercially available inhibitors. Depletion of Igf2bp3 sensitized MLL-AF4 leukemia to the effects of menin-MLL inhibition on cell growth and leukemic initiating cells in vitro. Mechanistically, we found that both Igf2bp3 depletion and menin-MLL inhibition led to increased differentiation in vitro and in vivo, seen in functional readouts and by gene expression analyses. IGF2BP3 knockdown had a greater effect on increasing survival and attenuating disease than pharmacologic menin-MLL inhibition with small molecule MI-503 alone and showed enhanced antileukemic effects in combination. Our work shows that IGF2BP3 is an oncogenic amplifier of MLL-AF4-mediated leukemogenesis and a potent therapeutic target, providing a paradigm for targeting leukemia at both the transcriptional and posttranscriptional level.


Assuntos
Leucemia , Proteína de Leucina Linfoide-Mieloide , Humanos , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Leucemia/tratamento farmacológico , Leucemia/genética , Leucemia/metabolismo , Fatores de Transcrição , Diferenciação Celular , Proteínas de Fusão Oncogênica/genética
14.
J Mater Chem B ; 11(43): 10418-10432, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37877327

RESUMO

Medical implants are frequently used in medicine and reconstructive surgery to treat various pathological and anatomical conditions. However, over time, biofilm formation on the surface of these implants can cause recurrent infections and subsequent inflammatory responses in the host, resulting in tissue damage, necrosis, and re-hospitalization. To address these implant-associated infections, the best approach is to create antimicrobial coatings. Here, we report the fabrication of a biocompatible, non-leaching, and contact-based antibacterial coating for implants using quaternary pullulan functionalized MoS2 (MCP) glycosheets. The cationic MCP glycosheets were coated on the surfaces of polydopamine-modified stainless steel and polyvinyl fluoride substrates through a simple process of electrostatic interaction. The developed coating showed excellent antibacterial activity (>99.5%) against E. coli and S. aureus that remained stable over 30 days without leaching out of the substrates and retained its antibacterial activity. MCP-coated implants did not induce any acute or sub-chronic toxicity to mammalian cells, both in vitro and in vivo. Furthermore, MCP coating prevented S. aureus colonization on stainless steel implants in a mouse model of implant-associated infection. The MCP coating developed in this study represents a simple, safe, and effective antibacterial coating for preventing implant-associated infections.


Assuntos
Molibdênio , Staphylococcus aureus , Camundongos , Animais , Molibdênio/farmacologia , Escherichia coli , Aço Inoxidável , Biofilmes , Antibacterianos/farmacologia , Mamíferos
15.
J Mech Behav Biomed Mater ; 148: 106200, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37907060

RESUMO

Hydroxyapatite (HAp) exists as an inorganic and crystalline composition present in bones and dental enamel, and hence can be utilized as a direct element or as part of the composition of biomaterials and implants for dental and orthopaedic applications. Listed below are a few synthesis techniques for HAp that are listed in the literature: solid-state and mechano-chemical methods (dry methods), wet chemical precipitation and sol-gel methods (wet methods), and combustion and pyrolysis methods (high-temperature processes). Nevertheless, there are new and more productive techniques that result in HAp with a regulated morphology, such as the Schiff base method, which, on reaction with calcium and phosphate precursors, forms chelating complexes to produce HAp nuclei. This research paper presents the comparison in characteristics between HAp synthesized using Schiff base (HAp-SB), wet chemical precipitation (HAp-WC) methods, and commercial HAp (HAp-CM) in their powdered and pelleted form. The average size of HAp-WC particles in the spherical form was found to be 603 nm ± 176, HAp-SB were found to have rod-like morphology, which is very similar to human bone-like HAp, with an average length and width of 1522 nm ± 759 and 400 nm ± 112, respectively, and HAp-CM were found to have spherical morphology with dimensions of 52 nm ± 25. Biological studies show that cell viability of HAp-SB pellet (202.01% ± 8.16) seemed to have higher cell proliferation properties than HAp-WC pellet (145.7% ± 5.11) and HAp-CM pellet (71.53% ± 3.61) due to its higher aspect ratio, and hence higher surface area for the cells to adhere. In a detailed study, it is observed that both techniques had their advantages, and there were no significant disadvantages observed.


Assuntos
Durapatita , Bases de Schiff , Humanos , Durapatita/química , Materiais Biocompatíveis/química , Osso e Ossos , Precipitação Química
16.
J Exp Clin Cancer Res ; 42(1): 231, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37670323

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric hematological malignancy, with ETV6::RUNX1 being the most prevalent translocation whose exact pathogenesis remains unclear. IGF2BP1 (Insulin-like Growth Factor 2 Binding Protein 1) is an oncofetal RNA binding protein seen to be specifically overexpressed in ETV6::RUNX1 positive B-ALL. In this study, we have studied the mechanistic role of IGF2BP1 in leukemogenesis and its synergism with the ETV6::RUNX1 fusion protein. METHODS: Gene expression was analyzed from patient bone marrow RNA using Real Time RT-qPCR. Knockout cell lines were created using CRISPR-Cas9 based lentiviral vectors. RNA-Seq and RNA Immunoprecipitation sequencing (RIP-Seq) after IGF2BP1 pulldown were performed using the Illumina platform. Mouse experiments were done by retroviral overexpression of donor HSCs followed by lethal irradiation of recipients using a bone marrow transplant model. RESULTS: We observed specific overexpression of IGF2BP1 in ETV6::RUNX1 positive patients in an Indian cohort of pediatric ALL (n=167) with a positive correlation with prednisolone resistance. IGF2BP1 expression was essential for tumor cell survival in multiple ETV6::RUNX1 positive B-ALL cell lines. Integrated analysis of transcriptome sequencing after IGF2BP1 knockout and RIP-Seq after IGF2BP1 pulldown in Reh cell line revealed that IGF2BP1 targets encompass multiple pro-oncogenic signalling pathways including TNFα/NFκB and PI3K-Akt pathways. These pathways were also dysregulated in primary ETV6::RUNX1 positive B-ALL patient samples from our center as well as in public B-ALL patient datasets. IGF2BP1 showed binding and stabilization of the ETV6::RUNX1 fusion transcript itself. This positive feedback loop led to constitutive dysregulation of several oncogenic pathways. Enforced co-expression of ETV6::RUNX1 and IGF2BP1 in mouse bone marrow resulted in marrow hypercellularity which was characterized by multi-lineage progenitor expansion and strong Ki67 positivity. This pre-leukemic phenotype confirmed their synergism in-vivo. Clonal expansion of cells overexpressing both ETV6::RUNX1 and IGF2BP1 was clearly observed. These mice also developed splenomegaly indicating extramedullary hematopoiesis. CONCLUSION: Our data suggest a combined impact of the ETV6::RUNX1 fusion protein and RNA binding protein, IGF2BP1 in activating multiple oncogenic pathways in B-ALL which makes IGF2BP1 and these pathways as attractive therapeutic targets and biomarkers.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Animais , Camundongos , Subunidade alfa 2 de Fator de Ligação ao Core , Camundongos Knockout , Fosfatidilinositol 3-Quinases , Variante 6 da Proteína do Fator de Translocação ETS
17.
ACS Appl Bio Mater ; 6(10): 3946-3958, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37698377

RESUMO

Primary bone tumors such as Ewing sarcoma, osteosarcoma, and chondrosarcoma, secondary bone tumors developed from progressive malignancies, and metastasized bone tumors are more prevalent and studied descriptively through biology and medical research. Less than 0.2% of cancer diagnoses are caused by rare bone-originating tumors, which despite being rare are particularly difficult due to their high death rates and substantial disease burden. A giant cell tumor of bone (GCTB) is an intramurally invasive but rare and benign type of bone tumor, which seldom metastasizes. The most often prescribed medication for GCTB is Denosumab, a RANKL (receptor activator of nuclear factor κB ligand) inhibitor. Because pharmaceutical drug companies rely on two-dimensional and animal models, current approaches for investigating the diverse nature of tumors are insufficient. Cell line based medication effectiveness and toxicity studies cannot predict tumor response to antitumor medicines. It has already been investigated in detail why molecular pathways do not reproduce in vitro, a phenomenon known as flat biology. Due to physiological differences between human beings and animals, animal models do not succeed in identifying side effects of the treatment, emulating metastatic growth, and establishing the link between cancer and the immune system. This review summarizes and discusses GCTB, the disease, its cellular composition, various bone tumor models, and their properties and utilization in research. As a result, this study delves deep into in vitro testing, which is vital for scientists and physicians in various fields, including pharmacology, preclinical investigations, tissue engineering, and regenerative medicine.

18.
Cancers (Basel) ; 15(18)2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37760460

RESUMO

BACKGROUND: Although IGF2BP3 has been implicated in tumorigenesis and poor outcomes in multiple cancers, its role in soft-tissue sarcoma (STS) remains unknown. Preliminary data have suggested an association with IGF2BP3 expression among patients with well-differentiated/dedifferentiated liposarcoma (WD/DD LPS), a disease where molecular risk stratification is lacking. METHODS: We examined the survival associations of IGF2BP3 via univariate and multivariate Cox regression in three unique datasets: (1) the Cancer Genome Atlas (TCGA), (2) an in-house gene microarray, and (3) an in-house tissue microarray (TMA). A fourth dataset, representing an independent in-house TMA, was used for validation. RESULTS: Within the TCGA dataset, IGF2BP3 expression was a poor prognostic factor uniquely in DD LPS (OS 1.6 vs. 5.0 years, p = 0.009). Within the microarray dataset, IGF2BP3 expression in WD/DD LPS was associated with worse survival (OS 7.7 vs. 21.5 years, p = 0.02). IGF2BP3 protein expression also portended worse survival in WD/DD LPS (OS 3.7 vs. 13.8 years, p < 0.001), which was confirmed in our validation cohort (OS 2.7 vs. 14.9 years, p < 0.001). In the multivariate model, IGF2BP3 was an independent risk factor for OS, (HR 2.55, p = 0.034). CONCLUSION: IGF2BP3 is highly expressed in a subset of WD/DD LPS. Across independent datasets, IGF2BP3 is also a biomarker of disease progression and worse survival.

19.
Analyst ; 148(20): 5279-5290, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37743715

RESUMO

In this study, a highly sensitive and efficient surface-enhanced Raman spectroscopy (SERS) substrate was developed using Au dogbone nanorattles (Au-DBNRTs) deposited on a 3D wrinkled polymeric heat shrink film. The plasmonic structures of Au-DBNRTs, which possess a solid gold dogbone-shaped core and a thin, porous gold shell, and Au nanorod nanorattles (Au-NRNRTs), which have a rod-shaped core, were synthesized and their SERS performance was evaluated. Au-DBNRTs exhibited better Raman signal enhancement. The substrate was used to detect the pesticide thiabendazole with a limit of detection of up to 10-8 M. The unique optical properties and geometry of the Au-DBNRT nanoparticles, which have portruding corners in the vicinity of the metal shell, along with the shrinkage of the film after heat treatment, led to the creation of a 3D surface morphology, resulting in the generation of plasmonic electromagnetic hot spots. The fabricated substrate achieved an enhancement factor of 2.77 × 1010 for BDT, and the detection limit was 10-13 M. The current work offers a simple, cost-effective, and sensitive SERS substrate design that has great potential for sensing and detecting trace analytes.

20.
ACS Appl Mater Interfaces ; 15(36): 43124-43134, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37665350

RESUMO

Despite recent developments, surface-enhanced Raman spectroscopy (SERS) applications face challenges in achieving both high sensitivity and uniform Raman signals over a large area. Using the directional self-assembly of plasmonic nanoparticles in lattice structures, we show how one can increase the SERS signal 43-fold over randomly aligned gold nanoparticles without relying on the photoluminescence of Rhodamine 6G. For this study, we have chosen the lattice constant for an off-resonant case that matches the lattice resonance and super-radiant plasmon mode along the particle chain. Supported by electromagnetic simulations, we systematically analyze the radiative components of the plasmon modes by varying the particle size while keeping the lattice periodicity constant. We perform polarization-dependent SERS measurements and compare them with other standard SERS excitation wavelengths. Using the self-assembled plasmonic particle lattice, we have developed an effective SERS substrate that provides a significantly higher signal with 73% less surface coverage. This colloidal approach enables the cost-effective and scalable fabrication of highly sensitive, uniform, and polarization-dependent SERS substrates.

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