DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes.

Funder: addenbrooke's charitable trust, cambridge university hospital

Rationalisation of antifungal properties of α-helical pore-forming peptide, mastoparan B

The high mortality associated with invasive fungal infections, narrow spectrum of available antifungals, and increasing evolution of antifungal resistance necessitate the development of alternative therapies. Host defense peptides are regarded as the first line of defense against microbial invasion in both vertebrates and invertebrates. In this work, we investigated the effectiveness of four naturally occurring pore-forming antimicrobial peptides (melittin, magainin 2, cecropin A, and mastoparan B) against a panel of clinically relevant pathogens, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida glabrata. We present data on the antifungal activities of the four pore-forming peptides, assessed with descriptive statistics, and their cytocompatibility with cultured human cells. Among the four peptides, mastoparan B (MB) displayed potent antifungal activity, whereas cecropin A was the least potent. We show that MB susceptibility of phylogenetically distant non-candida albicans can vary and be described by different intrinsic physicochemical parameters of pore-forming α-helical peptides. These findings have potential therapeutic implications for the design and development of safe antifungal peptide-based drugs.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionThis research was funded by the Singapore Ministry of Health’s National Medical Research Council (NMRC) under its Centre Grant Program—Optimization of Core Platform Technologies for Ocular Research (INCEPTOR)-NMRC/CG/M010/2017, Open Fund—Large Collaborative Grant (OFLCG18May-0028), the SingHealth Foundation (SHF/FG663P/2017) and the Agency for Science, Technology and Research (A*STAR) under its Wound Care Innovation for the Tropics (WCIT) Industry Alignment Fund Pre-Positioning (IAF-PP) grant (H17/01/a0/0K9). The work was also supported by the Singapore Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 1 grants (2020-T1-001-062 and R-148-000-309-114). The APC was funded by R1875/3/2022

Electrospun aligned PCLl/gelatin scaffolds mimicking the skin ECM for effective antimicrobial wound dressings

Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care. Biocompatible antimicrobial agents, e.g., ε-polylysine (ε-PL), provide a broad spectrum of antibacterial properties and support dermal cell growth. Here, ε-PL was incorporated into polycaprolactone (PCL)/gelatin electrospun scaffolds collected at varying rotation speeds. Then, the samples were crosslinked using dopamine hydrochloride to provide highly proliferative dressings with broad antimicrobial activity. The morphological study showed that the electrospun wound dressings were smooth, continuous, and bead-free, with a mean diameter ranging from 267 ± 7 to 331 ± 8 nm for all random and aligned nanofibers. The fiber alignment of the electrospun PCL/gelatin scaffolds improved their tensile strength and modulus. Moreover, nanofiber mats are highly hydrophilic, which is crucial for an efficient wound dressing. The samples also demonstrated high antimicrobial properties against common wound bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus (SA), Escherichia coli (EC), Acinetobacter baumannii (AB), and Pseudomonas aeruginosa (PA). Mammalian cell proliferation and morphology assays involving primary human dermal fibroblasts (hDFs) and immortalized keratinocytes (HaCaT) showed excellent biocompatibility of the electrospun mats and remarkably aligned mats. Furthermore, aligned mats showed more cell migration than randomly oriented mats, which is desirable for more efficient wound healing. Therefore, it can be concluded that aligned PCL/gelatin mats containing ε-PL are promising for potential use in wound dressings. Graphical Abstract: [Figure not available: see fulltext.].Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityE.R.G. acknowledges the financial support from the Singapore International Graduate Award (SINGA). R.L. thanks funding support from the Duke-NUS Khoo Bridge Funding Award (Duke-NUS-KBrFA/2021/0044). N.K.V. acknowledges funding support from the Singapore Ministry of Education (MOE) under its MOE Academic Research Fund (AcRF) Tier 1 Grant (RG26/20) and the Agency for Science, Technology and Research (A*STAR) under its Wound Care Innovation for the Tropics (WCIT) Industry Alignment Fund Pre-Positioning (IAF-PP) Grant (H17/01/a0/0K9). B.H.S.W. and Z.S.P. were provided Ph.D. fellowships by HealthTech NTU and Lee Kong Chian School of Medicine, Nanyang Technological University Singapore

Obstacles for T-lymphocytes in the tumour microenvironment: therapeutic challenges, advances and opportunities beyond immune checkpoint

The tumour microenvironment (TME) imposes a major obstacle to infiltrating T-lymphocytes and suppresses their function. Several immune checkpoint proteins that interfere with ligand/receptor interactions and impede T-cell anti-tumour responses have been identified. Immunotherapies that block immune checkpoints have revolutionized the treatment paradigm for many patients with advanced-stage tumours. However, metabolic constraints and soluble factors that exist within the TME exacerbate the functional exhaustion of tumour-infiltrating T-cells. Here we review these multifactorial constraints and mechanisms - elevated immunosuppressive metabolites and enzymes, nutrient insufficiency, hypoxia, increased acidity, immense amounts of extracellular ATP and adenosine, dysregulated bioenergetic and purinergic signalling, and ionic imbalance - that operate in the TME and collectively suppress T-cell function. We discuss how scientific advances could help overcome the complex TME obstacles for tumour-infiltrating T-lymphocytes, aiming to stimulate further research for developing new therapeutic strategies by harnessing the full potential of the immune system in combating cancer.Ministry of Education (MOE)Ministry of Health (MOH)Nanyang Technological UniversityNational Medical Research Council (NMRC)National Research Foundation (NRF)Published versionThis research was supported, in part, by the Singapore Ministry of Education (MOE) under its MOE Academic Research Fund (AcRF) Tier 2 (MOE2017-T2-2-004) and Tier 1 (2020-T1-001-062) grants, and the National Research Foundation Singapore under its Open Fund - Large Collaborative Grant (OFLCG18May-0028) and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC). N.F.G. acknowledges funding support from the NMRC Transition Award (NMRC/TA/0051/2016) and the NMRC Centre Grant (TETRAD 2). B.H.S.W. and Z.S.P. were provided with PhD fellowship by HealthTech NTU and Lee Kong Chian School of Medicine, Nanyang Technological University Singapore

Effects of electrode materials on solution-processed polyvinylidene fluoride-based piezoelectric nanogenerators: do they matter?

Numbers of energy harvesting studies have reported that using the appropriate electrode materials could enhance the electrical output performance of the energy harvesters. In this work, we fabricated polyvinylidene fluoride (PVDF)-based piezoelectric nanogenerators (PENGs) using the solution-process method. Different combinations of silver nanowires, indium-tin-oxide (ITO), and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate were used as top and bottom electrodes to investigate the effect of electrode materials on the electrical output performance. The open-circuit voltage (VOC), short-circuit current (ISC), the charge generated, instantaneous areal power measured, and internal impedance were measured. The obtained data reveal no significant difference between the different electrode combinations, with a mean absolute deviation of 0.21 V, and 0.03 μA for VOC and ISC, respectively. Thereby, an equivalent circuit for a real capacitor is adopted to analyze further and identify the impedance manifestation attributed to the PVDF layer and electrode materials. Overall, the electrode materials have an insignificant impact on the electrical output performance of PVDF-based PENGs in this study. Nevertheless, the obtained data inciting that tuning the PVDF impedance by introducing the 2D MXene nanofillers approach could be useful information to improve the performance of solution-processed PVDF-based PENGs

DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes

10.1186/s12943-021-01437-0MOLECULAR CANCER20