2458 Despite dramatic improvements in treatment over the past 40 years, acute lymphoblastic leukemia (ALL) remains one of the most common causes of death from disease in childhood. Glucocorticoids are among the most effective agents used in the treatment of lymphoid malignancies, and patient response to treatment is an important determinant of long-term outcome in childhood ALL. In spite of its clinical significance, the molecular basis of glucocorticoid resistance is still poorly understood. The aim of this study was to develop an experimental model system to define clinically relevant mechanisms of glucocorticoid resistance in childhood ALL. An in vivo model of childhood ALL has been developed in our laboratory, using patient biopsies established as xenografts in immune-deficient nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice. This model is highly representative of the human disease (Lock et al., Blood, 99: 4100-4108, 2002). The in vivo responses of these xenografts to the glucocorticoid dexamethasone (DEX) correlated significantly with patient outcome (p 1 μM) in xenografts from six patients, five of whom died of their disease. In contrast, four DEX-sensitive xenografts (IC50 values 2-fold in sensitive xenografts within 8 hours of treatment. In contrast, Bim induction was dramatically attenuated in DEX-resistant xenografts. These results have identified a clinically significant and novel mechanism of glucocorticoid resistance in childhood ALL, which occurs downstream of receptor-ligand interactions, but upstream of the signalling pathway resulting in Bim induction and apoptosis.

Novel mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia.

Ferroptosis is a newly discovered form of regulated cell death that is the nexus between metabolism, redox biology, and human health. Emerging evidence shows the potential of triggering ferroptosis for cancer therapy, particularly for eradicating aggressive malignancies that are resistant to traditional therapies. Recently, there has been a great deal of effort to design and develop anticancer drugs based on ferroptosis induction. Recent advances of ferroptosis-inducing agents at the intersection of chemistry, materials science, and cancer biology are presented. The basis of ferroptosis is summarized first to highlight the feasibility and characteristics of triggering ferroptosis for cancer therapy. A literature review of ferroptosis inducers (including small molecules and nanomaterials) is then presented to delineate their design, action mechanisms, and anticancer applications. Finally, some considerations for research on ferroptosis inducers are spotlighted, followed by a discussion on the challenges and future development directions of this burgeoning field.

Recent Progress in Ferroptosis Inducers for Cancer Therapy

In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.

https://www.mdpi.com/2073-4409/8/8/886/pdf

Mesenchymal Stem Cells for Regenerative Medicine.

Cellulose nanocrystals and cellulose nanofibrils based hydrogels for biomedical applications.

3D printing alias additive manufacturing can transform 3D virtual models created by computer-aided design (CAD) into physical 3D objects in a layer-by-layer manner dispensing with conventional molding or machining. Since the incipiency, significant advancements have been achieved in understanding the process of 3D printing and the relationship of component, structure, property and application of the created objects. Because hydrogels are one of the most feasible classes of ink materials for 3D printing and this field has been rapidly advancing, this Review focuses on hydrogel designs and development of advanced hydrogel-based biomaterial inks and bioinks for 3D printing. It covers 3D printing techniques including laser printing (stereolithography, two-photon polymerization), extrusion printing (3D plotting, direct ink writing), inkjet printing, 3D bioprinting, 4D printing and 4D bioprinting. It provides a comprehensive overview and discussion of the tailorability of material, mechanical, physical, chemical and biological properties of hydrogels to enable advanced hydrogel designs for 3D printing. The range of hydrogel-forming polymers covered encompasses biopolymers, synthetic polymers, polymer blends, nanocomposites, functional polymers, and cell-laden systems. The representative biomedical applications selected demonstrate how hydrogel-based 3D printing is being exploited in tissue engineering, regenerative medicine, cancer research, in vitro disease modeling, high-throughput drug screening, surgical preparation, soft robotics and flexible wearable electronics. Incomparable by thermoplastics, thermosets, ceramics and metals, hydrogel-based 3D printing is playing a pivotal role in the design and creation of advanced functional (bio)systems in a customizable way. An outlook on future directions of hydrogel-based 3D printing is presented.

3D printing of hydrogels: Rational design strategies and emerging biomedical applications

Tissue engineering has become a promising strategy for repairing damaged cartilage and bone tissue Among the scaffolds for tissue-engineering applications, injectable hydrogels have demonstrated great potential for use as three-dimensional cell culture scaffolds in cartilage and bone tissue engineering, owing to their high water content, similarity to the natural extracellular matrix (ECM), porous framework for cell transplantation and proliferation, minimal invasive properties, and ability to match irregular defects In this review, we describe the selection of appropriate biomaterials and fabrication methods to prepare novel injectable hydrogels for cartilage and bone tissue engineering In addition, the biology of cartilage and the bony ECM is also summarized Finally, future perspectives for injectable hydrogels in cartilage and bone tissue engineering are discussed

/pdf/injectable-hydrogels-for-cartilage-and-bone-tissue-5yblito95w.pdf

Injectable hydrogels for cartilage and bone tissue engineering.

Aptasensors for pesticide detection

Point-of-care diagnostics for infectious diseases: From methods to devices.

Nanomaterial-induced ferroptosis for cancer specific therapy

Aptamers are short non-coding, single-stranded oligonucleotides (RNA or DNA) developed through Systematic Evolution of Ligands by Exponential enrichment (SELEX) in vitro. Similar to antibodies, aptamers can bind to specific targets with high affinity, and are considered promising therapeutic agents as they have several advantages over antibodies, including high specificity, stability, and non-immunogenicity. Furthermore, aptamers can be produced at a low cost and easily modified, and are, therefore, called “chemical antibodies”. In the past years, a variety of aptamers specifically bound to both breast cancer biomarkers and cells had been selected. Besides, taking advantage of nanomaterials, there were a number of aptamer-nanomaterial conjugates been developed and widely investigated for diagnostics and targeted therapy of breast cancer. In this short review, we first present a systematical review of various aptamer selection methods. Then, various aptamer-based diagnostic and therapeutic strategies of breast cancer were provided. Finally, the current problems, challenges, and future perspectives in the field were thoroughly discussed.

/pdf/aptamer-selection-and-applications-for-breast-cancer-3y84kxp2ud.pdf

Mei Liu

Papers

Injectable hydrogels for cartilage and bone tissue engineering.

Aptasensors for pesticide detection

Point-of-care diagnostics for infectious diseases: From methods to devices.

Nanomaterial-induced ferroptosis for cancer specific therapy

Aptamer selection and applications for breast cancer diagnostics and therapy.