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Tumor‐on‐chip (ToC) is crucial to bridge the gap between traditional cell culture experiments and in vivo models, allowing to recreate an in vivo‐like microenvironment in cancer research. ToC use microfluidics to provide fine‐tune control over environmental factors, high‐throughput screening, and reduce requirements of samples and reagents. However, creating these microfluidic devices requires skilled researchers and dedicated manufacturing equipment, making widespread adoption cumbersome and difficult. To address some bottlenecks and improve accessibility to ToC technology, innovative materials and fabrication processes are required. Polystyrene (PS) is a promising material for microfluidics due to its biocompatibility, affordability, and optical transparency. Herein, a fabrication process based on direct laser writing on thermosensitive PS, allowing the swift and economical crafting of devices with easy pattern alterations, is presented. For the first time, a device for cell culture fabricated only by PS is presented, allowing customizing and optimization for efficient cell culture approaches. These biochips support 2D and 3D cultures with comparable viability and proliferation kinetics to traditional 96‐well plates. The data show that gene and protein silencing efficiencies remain consistent across both chip and plate‐based cultures, either 2D culture or 3D spheroid format. Although simple, this approach might facilitate the use of customized chip‐based cancer models. [ABSTRACT FROM AUTHOR]

Advances in nanotechnology and medical science have spurred the development of engineered nanomaterials and nanoparticles with particular focus on their applications in biomedicine. In particular, gold nanoparticles (AuNPs) have been the focus of great interest, due to their exquisite intrinsic properties, such as ease of synthesis and surface functionalization, tunable size and shape, lack of acute toxicity and favorable optical, electronic, and physicochemical features, which possess great value for application in biodetection and diagnostics purposes, including molecular sensing, photoimaging, and application under the form of portable and simple biosensors (e.g., lateral flow immunoassays that have been extensively exploited during the current COVID‐19 pandemic). We shall discuss the main properties of AuNPs, their synthesis and conjugation to biorecognition moieties, and the current trends in sensing and detection in biomedicine and diagnostics. This article is categorized under:Diagnostic Tools > BiosensingDiagnostic Tools > In Vitro Nanoparticle‐Based SensingDiagnostic Tools > In Vivo Nanodiagnostics and Imaging [ABSTRACT FROM AUTHOR]

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%–30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient's resistance and disease relapse. Here, we report a Ph+ B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190BCR-ABL1 isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission. [ABSTRACT FROM AUTHOR]

Digital microfluidics (DMF) arises as the next step in the fast-evolving field of operation platforms for molecular diagnostics. Moreover, isothermal schemes, such as loop-mediated isothermal amplification (LAMP), allow for further simplification of amplification protocols. Integrating DMF with LAMP will be at the core of a new generation of detection devices for effective molecular diagnostics at point-of-care (POC), providing simple, fast, and automated nucleic acid amplification with exceptional integration capabilities. Here, we demonstrate for the first time the role of coupling DMF and LAMP, in a dedicated device that allows straightforward mixing of LAMP reagents and target DNA, as well as optimum temperature control (reaction droplets undergo a temperature variation of just 0.3 °C, for 65 °C at the bottom plate). This device is produced using low-temperature and low-cost production processes, adaptable to disposable and flexible substrates. DMF-LAMP is performed with enhanced sensitivity without compromising reaction efficacy or losing reliability and efficiency, by LAMP-amplifying 0.5 ng/μL of target DNA in just 45 min. Moreover, on-chip LAMP was performed in 1.5 μL, a considerably lower volume than standard bench-top reactions. [ABSTRACT FROM AUTHOR]

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the association between risk of obesity in the Portuguese population and two obesity-related single-nucleotide gene polymorphisms: fat-mass and obesity-associated (FTO) rs9939609 and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282. Patients and methods: A total of 194 Portuguese premenopausal female Caucasians aged between 18 and 50 years (95 with body mass index [BMI] ⩾30 g/m2, 99 controls with BMI 18.5-24.9 kg/m2) participated in this study. The association of the single-nucleotide polymorphisms with obesity was determined by odds ratio calculation with 95% confidence intervals. Results: Significant differences in allelic expression of FTO rs9939609 (P,0.05) were found between control and case groups, indicating a 2.5-higher risk for obesity in the presence of both risk alleles when comparing the control group with the entire obese group. A fourfold-higher risk was found for subjects with class III obesity compared to those with classes I and II. No significant differences in BMI were found between the control and case groups for PPARG rs1801282 (P.0.05). Conclusion: For the first time, a study involving an adult Portuguese population shows that individuals harboring both risk alleles in the FTO gene locus are at higher risk for obesity, which is in agreement to what has been reported for other European populations. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) cell culture using tumor spheroids provides a crucial platform for replicating tissue microenvironments. However, effective gene modulation via nanoparticle-based transfection remains a challenge, often facing delivery hurdles. Gold nanoparticles (AuNPs) with their tailored synthesis and biocompatibility, have shown promising results in two-dimensional (2D) cultures, nevertheless, they still require a comprehensive evaluation before they can reach its full potential on 3D models. While 2D cultures offer simplicity and affordability, they lack physiological fidelity. In contrast, 3D spheroids better capture in vivo conditions, enabling the study of cell interactions and nutrient distribution. These models are essential for investigating cancer behavior, drug responses, and developmental processes. Nevertheless, transitioning from 2D to 3D models demands an understanding of altered internalization mechanisms and microenvironmental influences. This study assessed ASO-AuNP conjugates for silencing the c-MYC oncogene in 2D cultures and 3D tumor spheroids, revealing distinctions in gene silencing efficiency and highlighting the microenvironment's impact on AuNP-mediated gene modulation. Herein, we demonstrate that increasing the number of AuNPs per cell by 2.6 times, when transitioning from a 2D cell model to a 3D spheroid, allows to attain similar silencing efficiencies. Such insights advance the development of targeted gene therapies within intricate tissue-like contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Oliveira, Fernandes and Baptista.)

Introduction: Delivery of therapeutic nanoparticles (NPs) to cancer cells represents a promising approach for biomedical applications. A key challenge for nanotechnology translation from the bench to the bedside is the low amount of administered NPs dose that effectively enters target cells. To improve NPs delivery, several studies proposed NPs conjugation with ligands, which specifically deliver NPs to target cells via receptor binding. One such example is epidermal growth factor (EGF), a peptide involved in cell signaling pathways that control cell division by binding to epidermal growth factor receptor (EGFR). However, very few studies assessed the influence of EGF present in the cell environment, on the cellular uptake of NPs., Methods: We tested if the stimulation of EGFR-expressing lung carcinomacells A549 with EGF affects the uptake of 59 nm and 422 nm silica (SiO 2 ) NPs. Additionally, we investigated whether the uptake enhancement can be achieved with gold NPs, suitable to downregulate the expression of cancer oncogene c-MYC ., Results: Our findings show that EGF binding to its receptor results in receptor autophosphorylation and initiate signaling pathways, leading to enhanced endocytosis of 59 nm SiO 2 NPs, but not 422 nm SiO 2 NPs. Additionally, we demonstrated an enhanced gold (Au) NPs endocytosis and subsequently a higher downregulation of c-MYC ., Discussion: These findings contribute to a better understanding of NPs uptake in the presence of EGF and that is a promising approach for improved NPs delivery., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Advances in nanotechnology and medical science have spurred the development of engineered nanomaterials and nanoparticles with particular focus on their applications in biomedicine. In particular, gold nanoparticles (AuNPs) have been the focus of great interest, due to their exquisite intrinsic properties, such as ease of synthesis and surface functionalization, tunable size and shape, lack of acute toxicity and favorable optical, electronic, and physicochemical features, which possess great value for application in biodetection and diagnostics purposes, including molecular sensing, photoimaging, and application under the form of portable and simple biosensors (e.g., lateral flow immunoassays that have been extensively exploited during the current COVID-19 pandemic). We shall discuss the main properties of AuNPs, their synthesis and conjugation to biorecognition moieties, and the current trends in sensing and detection in biomedicine and diagnostics. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging., (© 2022 Wiley Periodicals LLC.)