Nucleoside analogues have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with cancer or viral infections. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Here, we review new nucleoside analogues and associated compounds that are currently in preclinical or clinical development for the treatment of cancer and viral infections, and that aim to provide increased response rates and reduced side effects. We also highlight the different approaches used in the development of these drugs and the potential of personalized therapy.

Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a-chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects.

/pdf/a-review-of-digital-microfluidics-as-portable-platforms-for-8nnswvqnrs.pdf

A review of digital microfluidics as portable platforms for lab-on a-chip applications.

The rapid growth of research in the areas of chemical and biochemical sensors, lab-on-a-chip, mobile technology, and wearable electronics offers an unprecedented opportunity in the development of mobile and wearable point-of-care testing (POCT) systems for self-testing. Successful implementation of such POCT technologies leads to minimal user intervention during operation to reduce user errors; user-friendly, easy-to-use and simple detection platforms; high diagnostic sensitivity and specificity; immediate clinical assessment; and low manufacturing and consumables costs. In this review, we discuss recent developments in the field of highly integrated mobile and wearable POCT systems. In particular, aspects of sample handling platforms, recognition elements and sensing methods, and new materials for signal transducers and powering devices for integration into mobile or wearable POCT systems will be highlighted. We also summarize current challenges and future prospects for providing personal healthcare with sample-in result-out mobile and wearable POCT.

Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing

Guide to Selecting a Biorecognition Element for Biosensors.

Integration of isothermal amplification methods in microfluidic devices: Recent advances

The monitoring of DNA and RNA biomarkers freely circulating in the blood constitutes the basis of innovative cancer detection methods based on liquid biopsy. Such methods are expected to provide new opportunities for a better understanding of cancer disease at the molecular level, thus contributing to improved patient outcomes. Advanced biosensors can advance possibilities for cancer-related nucleic acid biomarkers detection. In this context, peptide nucleic acids (PNAs) play an important role in the fabrication of highly sensitive biosensors. This review provides an overview of recently described PNA-based biosensors for cancer biomarker detection. One of the most striking features of the described detection approaches is represented by the possibility to detect target nucleic acids at the ultra-low concentration with the capability to identify single-base mutations.

https://www.mdpi.com/1420-3049/22/11/1951/pdf

Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis.

Nucleic-acid amplification is a crucial step in nucleic-acid-sequence-detection assays. The use of digital microfluidic devices to miniaturize amplification techniques reduces the required sample volume and the analysis time and offers new possibilities for process automation and integration in a single device. The recently introduced droplet polymerase-chain-reaction (PCR) amplification methods require repeated cycles of two or three temperature-dependent steps during the amplification of the nucleic-acid target sequence. In contrast, low-temperature isothermal-amplification methods have no need for thermal cycling, thus requiring simplified microfluidic-device features. Here, the combined use of digital microfluidics and molecular-beacon (MB)-assisted isothermal circular-strand-displacement polymerization (ICSDP) to detect microRNA-210 sequences is described. MicroRNA-210 has been described as the most consistently and predominantly upregulated hypoxia-inducible factor. The nmol L−1–pmol L−1 detection capabilities of the method were first tested by targeting single-stranded DNA sequences from the genetically modified Roundup Ready soybean. The ability of the droplet-ICSDP method to discriminate between full-matched, single-mismatched, and unrelated sequences was also investigated. The detection of a range of nmol L−1–pmol L−1 microRNA-210 solutions compartmentalized in nanoliter-sized droplets was performed, establishing the ability of the method to detect as little as 10−18 mol of microRNA target sequences compartmentalized in 20 nL droplets. The suitability of the method for biological samples was tested by detecting microRNA-210 from transfected K562 cells.

Maria Chiara Giuffrida

Papers

Integration of isothermal amplification methods in microfluidic devices: Recent advances

Peptide Nucleic Acid-Based Biosensors for Cancer Diagnosis.

Isothermal circular-strand-displacement polymerization of DNA and microRNA in digital microfluidic devices

Ultrasensitive detection of lysozyme in droplet-based microfluidic devices.

Synthesis of n-squalenoyl cytarabine and evaluation of its affinity with phospholipid bilayers and monolayers