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Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could push current technological frontiers and provide new and innovative solutions for immune-related disorders and diseases without off-target effects. These materials enable targeted interactions with immune cells, thereby enhancing the effectiveness of checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. Moreover, they allow for fine-tuning of immune responses while minimizing side effects. At the intersection of nanotechnology and immunology, nanomaterial-based platforms have immense potential to revolutionize patient-centered immunotherapy and reshape disease management. By prioritizing safety, customization, and compliance with regulatory standards, these systems can make significant contributions to precision medicine, thereby significantly impacting the healthcare landscape.
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Worldwide urbanization and subsequent migration have accelerated the emergence and spread of diverse novel human diseases. Among them, diseases caused by viruses could result in epidemics, typified by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which hit the globe towards the end of December 2019. The global battle against SARS-CoV-2 has reignited interest in finding alternative treatments for viral infections. The marine world offers a large repository of diverse and unique bioactive compounds. Over the years, many antiviral compounds from marine organisms have been isolated and tested in vitro and in vivo. However, given the increasing need for alternative treatment, in silico analysis appears to provide a time- and cost-effective approach to identifying the potential antiviral compounds from the vast pool of natural metabolites isolated from marine organisms. In this perspective review, we discuss marine-derived bioactive metabolites as potential therapeutics for all known disease-causing viruses including the SARS-CoV-2. We demonstrate the efficacy of marine-derived bioactive metabolites in the context of various antiviral activities and their in silico, in vitro, and in vivo capacities.
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In the original publication [...].
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Hernia repair is one of the most frequently performed world-wide surgical procedures in which hernia meshes are becoming increasingly used. Polypropylene (PP) mesh implants reduce the risk of recurrence and post-operative pain, although many other risks are associated with it, such as bacterial infection. In this study we developed PP meshes coated with the well-known antimicrobial compound, benzalkonium chloride (BAK) by dip-coating. Several dilutions (40, 20, 30, 10, 7.5, 5, 2.5, 1, 0.5, 0.1 and 0.05 % v/v) of commercial BAK solution (BAK diluted in 70 % ethyl alcohol at 0.1 % w/v) were used to produce antimicrobial meshes with different amounts of BAK. The dip-coating treatment with low concentrations of BAK (1, 0.5, 0.1 and 0.05 % v/v dilutions) was found to have biocompatible results in fibroblast. The use of 0.1 and 0.05 % v/v dilutions (PP meshes with up to â¼2 % w/w of BAK) showed proliferative activity on fibroblast cells, indicating that these novel antimicrobial meshes show great promise for hernia repair due to their ability to prevent infections while inducing fibroblast proliferation.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the rapidly evolving RNA virus behind the COVID-19 pandemic, has spawned numerous variants since its 2019 emergence. The multifunctional Nonstructural protein 14 (NSP14) enzyme, possessing exonuclease and messenger RNA (mRNA) capping capabilities, serves as a key player. Notably, single and co-occurring mutations within NSP14 significantly influence replication fidelity and drive variant diversification. This study comprehensively examines 120 co-mutations, 68 unique mutations, and 160 conserved residues across NSP14 homologs, shedding light on their implications for phylogenetic patterns, pathogenicity, and residue interactions. Quantitative physicochemical analysis categorizes 3953 NSP14 variants into three clusters, revealing genetic diversity. This research underscoresthe dynamic nature of SARS-CoV-2 evolution, primarily governed by NSP14 mutations. Understanding these genetic dynamics provides valuable insights for therapeutic and vaccine development.
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COVID-19 , Exorribonucleases , SARS-CoV-2 , Proteínas não Estruturais Virais , Humanos , COVID-19/genética , Exorribonucleases/química , Exorribonucleases/genética , Exorribonucleases/metabolismo , Mutação/genética , Pandemias , Filogenia , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Replicação Viral/genética , Proteínas não Estruturais Virais/metabolismoRESUMO
Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.
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Neoplasias Encefálicas , Glioblastoma , RNA não Traduzido , Receptores Notch , Transdução de Sinais , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Glioblastoma/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , RNA não Traduzido/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão GênicaRESUMO
The complicated relationships between autoimmunity, COVID-19, and COVID-19 vaccinations are described, giving insight into their intricacies. Antinuclear antibodies (ANA), anti-Ro/SSA, rheumatoid factor, lupus anticoagulant, and antibodies against interferon (IFN)-I have all been consistently found in COVID-19 patients, indicating a high prevalence of autoimmune reactions following viral exposure. Furthermore, the discovery of human proteins with structural similarities to SARS-CoV-2 peptides as possible autoantigens highlights the complex interplay between the virus and the immune system in initiating autoimmunity. An updated summary of the current status of COVID-19 vaccines is presented. We present probable pathways underpinning the genesis of COVID-19 autoimmunity, such as bystander activation caused by hyperinflammatory conditions, viral persistence, and the creation of neutrophil extracellular traps. These pathways provide important insights into the development of autoimmune-related symptoms ranging from organ-specific to systemic autoimmune and inflammatory illnesses, demonstrating the wide influence of COVID-19 on the immune system.
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Autoimunidade , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Autoimunidade/imunologia , Doenças Autoimunes/imunologia , Autoantígenos/imunologiaRESUMO
Acetic acid, a colourless liquid organic acid with a characteristic acrid smell, is obtained naturally and has applications in both the food and pharmaceutical industries. It has been reported to have beneficial uses for lifestyle-related diseases, and its efficient disinfectant properties are well known. In this study, an alginate crosslinked with Ca2+ hydrogel film was treated with acetic acid to explore its biological properties for biomedicine. The results showed that the novel calcium alginate/acetic acid film was biocompatible in vitro using human keratinocyte cells and in vivo with Caenorhabditis elegans. It also had antiviral properties against enveloped and non-enveloped viruses and anticancer properties against melanoma and colon cancer cells. This novel film thus showed promise for the biomedical and pharmaceutical industries, with applications for fabricating broad-spectrum antiviral and anticancer materials.
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BACKGROUND: Biofilm formation on medical device surfaces is a persistent problem that shelters bacteria and encourages infections and implant rejection. One promising approach to tackle this problem is to coat the medical device with an antimicrobial material. In this work, for the first time, we impart antimicrobial functionality to Ti3Au intermetallic alloy thin film coatings, while maintaining their superior mechanical hardness and biocompatibility. METHODS: A mosaic Ti sputtering target is developed to dope controlled amounts of antimicrobial elements of Ag and Cu into a Ti3Au coating matrix by precise control of individual target power levels. The resulting Ti3Au-Ag/Cu thin film coatings are then systematically characterised for their structural, chemical, morphological, mechanical, corrosion, biocompatibility-cytotoxicity and antimicrobial properties. RESULTS: X-ray diffraction patterns reveal the formation of a super hard ß-Ti3Au phase, but the thin films undergo a transition in crystal orientation from (200) to (211) with increasing Ag concentration, whereas introduction of Cu brings no observable changes in crystal orientation. Scanning and transmission electron microscopy analysis show the polyhedral shape of the Ti3Au crystal but agglomeration of Ag particles between crystal grains begins at 1.2 at% Ag and develops into large granules with increasing Ag concentration up to 4.1 at%. The smallest doping concentration of 0.2 at% Ag raises the hardness of the thin film to 14.7 GPa, a 360% improvement compared to the â¼4 GPa hardness of the standard Ti6Al4V base alloy. On the other hand, addition of Cu brings a 315-330% improvement in mechanical hardness of films throughout the entire concentration range of 0.5-7.1 at%. The thin films also show good electrochemical corrosion resistance and a > tenfold reduction in wear rate compared to Ti6Al4V alloy. All thin film samples exhibit very safe cytotoxic profiles towards L929 mouse fibroblast cells when analysed with Alamar blue assay, with ion leaching concentrations lower than 0.2 ppm for Ag and 0.08 ppm for Cu and conductivity tests reveal the positive effect of increased conductivity on myogenic differentiation. Antimicrobial tests show a drastic reduction in microbial survival over a short test period of < 20 min for Ti3Au films doped with Ag or Cu concentrations as low as 0.2-0.5 at%. CONCLUSION: Therefore, according to these results, this work presents a new antimicrobial Ti3Au-Ag/Cu coating material with excellent mechanical performance with the potential to develop wear resistant medical implant devices with resistance to biofilm formation and bacterial infection.
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Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media.
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Oryza , Poluentes Químicos da Água , Humanos , Oryza/química , Água , Corantes/química , Adsorção , Cinética , Poluentes Químicos da Água/análise , Concentração de Íons de HidrogênioRESUMO
Water treatment is crucial in solving the rising people's appetite for water and global water shortages. Carbon nanotubes (CNTs) have considerable promise for water treatment because of their adjustable and distinctive arbitrary, physical, as well as chemical characteristics. This illustrates the benefits and risks of integrating CNT into the traditional water treatment resource. Due to their outstanding adsorbent ability and chemical and mechanical properties, CNTs have gained global consideration in environmental applications. The desalination and extraction capability of CNT were improved due to chemical or physical modifications in pure CNTs by various functional groups. The CNT-based composites have many benefits, such as antifouling performance, high selectivity, and increased water permeability. Nevertheless, their full-scale implementations are still constrained by their high costs. Functionalized CNTs and their promising nanocomposites to eliminate contaminants are advised for marketing and extensive water/wastewater treatment.
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Nanotubos de Carbono , Purificação da Água , Humanos , Nanotubos de Carbono/químicaRESUMO
The global COVID-19 pandemic has warned scientists of the requirement to look for new antimicrobial compounds to prevent infection by this type of viral pathogen. Natural compounds are becoming a promising avenue of research thanks to their renewable, biodegradable, and non-toxic properties. In this work, tiger nut milk's (TNM) antiviral properties, with and without sugar, were studied against enveloped and non-enveloped viruses. The antiviral properties of TNM were evaluated at different concentrations. The antiviral tests showed that TNM is antiviral against the enveloped bacteriophage phi 6, which is commonly used as a surrogate for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), although it did not have any antiviral effect against the non-enveloped bacteriophage MS2. We also found that adding sugar to this natural drink can improve its antiviral properties against enveloped viruses and render it antiviral against non-enveloped viruses like bacteriophage MS2. The antiviral activity of TNM depends on the TNM concentration. TNM is a natural bioproduct that could help to fight against viral infections and protect against a wide range of viral illnesses. These results confirm that the typical sweetened drink made from tiger nut extract and sugar (known as horchata in Spain) possesses broad-spectrum antiviral properties.
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Antivirais , COVID-19 , Humanos , Animais , Antivirais/farmacologia , Leite , Açúcares , Pandemias , SARS-CoV-2RESUMO
Chitosan films were prepared by solvent casting using an acetic acid-based solution. The films that were developed contained 15.49% of acetic acid solution (10% v/v) and showed biocompatibility in vitro in human keratinocyte HaCaT cells and potent antiviral activity against both enveloped and non-enveloped viruses. The results showed up to 99.98% and 99.92% viral inactivation against the phi 6 enveloped bacteriophage and MS2 non-enveloped bacteriophage, respectively, suggesting that this chitosan/acetic acid film is a promising material for biomedical applications that require biodegradable broad-spectrum antiviral materials.
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Quitosana , Vírus , Humanos , Antivirais/farmacologia , Quitosana/farmacologia , Ácido Acético/farmacologia , Inativação de Vírus , Materiais Biocompatíveis/farmacologiaRESUMO
Diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) have been receiving increasing attention in the last decade, particularly in the last 5 years, due to their potential to offer a combination of enhanced antimicrobial and mechanical performance. These multi-functional bioactive DLC coatings offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This review begins with an overview of the status and issues with current total joint implant materials and the state-of-the art in DLC coatings and their application to medical implants. A detailed discussion of recent advances in wear resistant bioactive DLC coatings is then presented with a focus on doping the DLC matrix with controlled quantities of Ag and Cu elements. It is shown that both Ag and Cu doping can impart strong antimicrobial potency against a range of Gram-positive and Gram-negative bacteria, but this is always accompanied so far by a reduction in mechanical performance of the DLC coating matrix. The article concludes with discussion of potential synthesis methods to accurately control bioactive element doping without jeopardising mechanical properties and gives an outlook to the potential long-term impact of developing a superior multifunctional bioactive DLC coating on implant device performance and patient health and wellbeing. STATEMENT OF SIGNIFICANCE: Multi-functional diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This article provides a critical review of the state-of-the-art in Ag and Cu doped DLC coatings, beginning with an overview of the current applications of DLC coatings in implant technology followed by a detailed discussion of Ag/Cu doped DLC coatings with particular focus on the relationship between their mechanical and antimicrobial performance. Finally, it ends with a discussion on the potential long-term impact of developing a truly multifunctional ultra-hard wearing bioactive DLC coating to extend the lifetime of total joint implants.
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Cobre , Prótese Articular , Humanos , Cobre/farmacologia , Prata/farmacologia , Carbono , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-PositivasRESUMO
Alginate is a highly promising biopolymer due to its non-toxic and biodegradable properties. Alginate hydrogels are often fabricated by cross-linking sodium alginate with calcium cations and can be engineered with highly desirable enhanced physical and biological properties for biomedical applications. This study reports on the anticancer, antiviral, antibacterial, in vitro, and in vivo toxicity, water absorption, and compound release properties of an alginate hydrogel crosslinked with calcium and different amounts of zinc cations. The results showed that the calcium alginate hydrogel film crosslinked with the highest amount of zinc showed similar water sorption properties to those of calcium alginate and released a suitable amount of zinc to provide anticancer activity against melanoma and colon cancer cells and has antibacterial properties against methicillin-resistant Staphylococcus epidermidis and antiviral activity against enveloped and non-enveloped viruses. This film is non-toxic in both in vitro in keratinocyte HaCaT cells and in vivo in the Caenorhabditis elegans model, which renders it especially promising for biomedical applications.
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PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes. PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS). CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.
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Neoplasias da Mama , Feminino , Humanos , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Recidiva Local de Neoplasia , Prognóstico , Receptores de Progesterona/genéticaRESUMO
Polymers in the form of films, fibers, nano- and microspheres, composites, and porous supports are promising biomaterials for a wide range of advanced biomedical applications: wound healing, controlling drug delivery, anti-cancer therapy, biosensors, stem cell therapy, and tissue engineering [...].
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Gold nanoparticles (AuNPs) are a fundamental building block of many applications across nanotechnology as they have excellent biosafety which make them promising for a broad range of biomedical applications. Here we explore their in vivo toxicity, cytotoxicity and proliferative capacity in human keratinocyte HaCaT cells, their ability to induce gene expression and their antiviral properties against a surrogate of SARS-CoV-2. These nanoparticles were characterized by transmission electron microscopy, dynamic light scattering and zeta potential. The results showed that these AuNPs with sizes ranging from 10 to 60 nm are non-toxic in vivo at any concentration up to 800 µg/mL. However, AuNP cytotoxicity in human HaCaT cells is time-dependent, so that concentrations of up to 300 µg/mL did not show any in vitro toxic effect at 3, 12 and 24 h, although higher concentrations were found to have some significant toxic activity, especially at 24 h. No significant proliferative activity was observed when using low AuNP concentrations (10, 20 and 40 µg/mL), while the AuNP antiviral tests indicated low or insignificant antiviral activity. Surprisingly, none of the 13 analyzed genes had their expressions modified after 24 h's exposure to AuNPs. Therefore, the results show that AuNPs are highly stable inactive materials and thus very promising for biomedical and clinical applications demanding this type of materials.
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COVID-19 , Nanopartículas Metálicas , Humanos , Ouro/toxicidade , Nanopartículas Metálicas/toxicidade , SARS-CoV-2 , Expressão GênicaRESUMO
This review explores the potential of photonic nanoparticles for cancer theranostics. Photonic nanoparticles offer unique properties and photonics capabilities that make them promising materials for cancer treatment, particularly in the presence of near-infrared light. However, the size of the particles is crucial to their absorption of near-infrared light and therapeutic potential. The limitations and challenges associated with the clinical use of photonic nanoparticles, such as toxicity, immune system clearance, and targeted delivery to the tumor are also discussed. Researchers are investigating strategies such as surface modification, biodegradable nanoparticles, and targeting strategies to improve biocompatibility and accumulation in the tumor. Ongoing research suggests that photonic nanoparticles have potential for cancer theranostics, further investigation and development are necessary for clinical use.
Tiny particles called 'photonic nanoparticles' can be used to help treat cancer. These particles have special properties that allow them to be used with special light to treat cancer. However, the size of the particles is really important, so scientists are trying to find ways to make sure they are the right size. There are also some challenges with using these particles in people, like making sure they don't harm the body and that they go to the right place. Scientists are working on ways to improve the safety of these particles and make sure they go where they need to.