Topical Reconstituted High-Density Lipoproteins Elicit Anti-Inflammatory Effects in Diabetic Wounds.

Reconstituted high-density lipoproteins (rHDL) improve wound healing in diabetes. We aimed to determine if rHDL elicit anti-inflammatory effects in diabetic wounds, as a mechanism to explain their wound healing benefits. Diabetes was induced using streptozotocin in C57Bl6/J mice.

Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders.

Treatment of diseases of oxidative stress through activation of the antioxidant nuclear factor E2-related factor 2 (NRF2) is limited by systemic side effects. We chemically functionalize the NRF2 activator monomethyl fumarate to require Baeyer-Villiger oxidation for release of the active drug at sites of oxidative stress. This prodrug reverses chronic pain in mice with reduced side effects and could be applied to other disorders of oxidative stress.

18 kDa Translocator protein (TSPO) is upregulated in rat brain after peripheral nerve injury and downregulated by diroximel fumarate.

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments.

From fibres to adhesives: evolution of spider capture threads from web anchors by radical changes in silk gland function.

Spider webs that serve as snares are one of the most fascinating and abundant type of animal architectures. In many cases they include an adhesive coating of silk lines-so-called viscid silk-for prey capture. The evolutionary switch from silk secretions forming solid fibres to soft aqueous adhesives remains an open question in the understanding of spider silk evolution.

AutoMitoNetwork: Software for analyzing mitochondrial networks in autofluorescence images to enable label-free cell classification.

High-resolution mitochondria imaging in combination with image analysis tools have significantly advanced our understanding of cellular function in health and disease. However, most image analysis tools for mitochondrial studies have been designed to work with fluorescently labeled images only. Additionally, efforts to integrate features describing mitochondrial networks with machine learning techniques for the differentiation of cell types have been limited.

Systemic and targeted activation of Nrf2 reverses doxorubicin-induced cognitive impairments and sensorimotor deficits in mice.

While cancer survivorship has increased due to advances in treatments, chemotherapy often carries long-lived neurotoxic side effects which reduce quality of life. Commonly affected domains include memory, executive function, attention, processing speed and sensorimotor function, colloquially known as chemotherapy-induced cognitive impairment (CICI) or "chemobrain". Oxidative stress and neuroimmune signaling in the brain have been mechanistically linked to the deleterious effects of chemotherapy on cognition and sensorimotor function.

Targeting macrophages with multifunctional nanoparticles to detect and prevent atherosclerotic cardiovascular disease.

Despite the emergence of novel diagnostic, pharmacological, interventional, and prevention strategies, atherosclerotic cardiovascular disease remains a significant cause of morbidity and mortality. Nanoparticle (NP)-based platforms encompass diverse imaging, delivery, and pharmacological properties that provide novel opportunities for refining diagnostic and therapeutic interventions for atherosclerosis at the cellular and molecular levels. Macrophages play a critical role in atherosclerosis and therefore represent an important disease-related diagnostic and therapeutic target, especially given their inherent ability for passive and active NP uptake.

Lectin-conjugated nanotags with high SERS stability: selective probes for glycans.

Surface-enhanced Raman scattering (SERS) nanotags functionalized with lectins as the biological recognition element can be used to target the carbohydrate portion of carbohydrate-carrying molecules (glycoconjugates). An investigation of the optical stability of such functionalized SERS nanotags is an essential initial step before future application and quantification of surface glycan biomarkers on cells and extracellular vesicles. Herein, we report an innovative approach to evaluate the SERS stability of lectin-conjugated nanotags by investigating any possible interfering lectin-lectin interactions in a mixture of different lectin-conjugated SERS nanotags, as well as an assessment of lectin-glycan interaction by mixing wheat germ agglutinin (WGA)-conjugated SERS nanotags with different glycoproteins.

ZIF-8 labelled a new electrochemical aptasensor based on PEI-PrGO/AuNWs for DON detection.

In this work, a novel ultrasensitive aptasensor for deoxynivalenol (DON) detection based on the polyethyleneimine-functionalised porous reduced graphene oxide loaded gold nanowires (PEI-PrGO/AuNWs) and methylene blue (MB)-labelled zeolitic imidazolate framework-8 (ZIF-8) signal amplification strategy was proposed. PEI-PrGO/AuNWs with large surface area and excellent conductivity were used as modification materials on bare gold electrodes, which could increase the combining of complementary strand (cDNA) on the electrode substrate and accelerate the electron transfer efficiency. Furthermore, a novel electrochemical signal probe was synthesized using streptavidin-modified zeolitic imidazolate framework-8 (ZIF-8/SA) as a carrier loaded with MB and reverse complementary chain (sDNA).

Exploring Photoswitchable Binding Interactions with Small-Molecule- and Peptide-Based Inhibitors of Trypsin.

The ability to photochemically activate a drug, both when and where needed, requires optimisation of the difference in biological activity between each isomeric state. As a step to this goal, we report small-molecule- and peptide-based inhibitors of the same protease-trypsin-to better understand how photoswitchable drugs interact with their biological target. The best peptidic inhibitor displayed a more than fivefold difference in inhibitory activity between isomeric states, whereas the best small-molecule inhibitor only showed a 3.

Simultaneous Imaging and Photodynamic-Enhanced Photothermal Inhibition of Cancer Cells Using a Multifunctional System Combining Indocyanine Green and Polydopamine-Preloaded Upconversion Luminescent Nanoparticles.

This work introduces a novel multifunctional system called UPIPF (upconversion-polydopamine-indocyanine-polyethylene-folic) for upconversion luminescent (UCL) imaging of cancer cells using near-infrared (NIR) illumination. The system demonstrates efficient inhibition of human hepatoma (HepG2) cancer cells through a combination of NIR-triggered photodynamic therapy (PDT) and enhanced photothermal therapy (PTT). Initially, upconversion nanoparticles (UCNP) are synthesized using a simple thermal decomposition method.

Designing Fluorescent Nuclear Permeable Peptidomimetics to Target Proliferating Cell Nuclear Antigen.

Human proliferating cell nuclear antigen (PCNA) is a critical mediator of DNA replication and repair, acting as a docking platform for replication proteins. Disrupting these interactions with a peptidomimetic agent presents as a promising avenue to limit proliferation of cancerous cells. Here, a p21-derived peptide was employed as a starting scaffold to design a modular peptidomimetic that interacts with PCNA and is cellular and nuclear permeable.

Engineered Cancer-Derived Small Extracellular Vesicle-Liposome Hybrid Delivery System for Targeted Treatment of Breast Cancer.

Cancer-derived small extracellular vesicles (sEVs) may be a promising drug delivery system that targets cancer cells due to their unique features, such as native homing ability, biological barrier crossing capability, and low immune response. However, the oncogenic cargos within them pose safety concerns, hence limiting their application thus far. We proposed using an electroporation-based strategy to extract the endogenous cargos from cancer-derived sEVs and demonstrated that their homing ability was still retained.

Fe/Zr-MOFs constructed by a sunlight-responsive ligand for efficient photocatalytic nitrogen fixation under ambient condition.

Photocatalytic nitrogen fixation opens new opportunities for sustainable and healthier futures, and developing effective and inexpensive photocatalysts is the key. We use the ligand 3,3',5,5'-azomellitic acid (Habtc) to connect with Fe clusters and Zr clusters to form stable metal-organic frameworks (MOFs) Fe-abtc and Zr-abtc, both of which are responsive to visible lights for nitrogen fixation. It is worth noting that the presence of NN in the ligand makes it respond to visible lights.

Detection of rare prostate cancer cells in human urine offers prospect of non-invasive diagnosis.

Two molecular cytology approaches, (i) time-gated immunoluminescence assay (TGiA) and (ii) Raman-active immunolabeling assay (RiA), have been developed to detect prostate cancer (PCa) cells in urine from five prostate cancer patients. For TGiA, PCa cells stained by a biocompatible europium chelate antibody-conjugated probe were quantitated by automated time-gated microscopy (OSAM). For RiA, PCa cells labeled by antibody-conjugated Raman probe were detected by Raman spectrometer.

Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide with high mortality, which is mainly due to the lack of reliable biomarkers for PDAC diagnosis/prognosis in the early stages and effective therapeutic strategies for the treatment. Cancer-derived small extracellular vesicles (sEVs), which carry various messages and signal biomolecules (e.g.

A new antioxidant made from a pterostilbene functionalized graphene nanocomposite as an efficient treatment for dry eye disease.

Dry eye disease is a common condition that affects the eyes. It is caused by problems with the tear film and the tear dynamics. Dry eye can be caused by an increase in the amount of reactive oxygen species (ROS) in the corneal epithelium.

Biological Sensing of Nitric Oxide in Macrophages and Atherosclerosis Using a Ruthenium-Based Sensor.

Macrophage-derived nitric oxide (NO) plays a critical role in atherosclerosis and presents as a potential biomarker. We assessed the uptake, distribution, and NO detection capacity of an irreversible, ruthenium-based, fluorescent NO sensor (Ru-NO) in macrophages, plasma, and atherosclerotic plaques. In vitro, incubation of Ru-NO with human THP1 monocytes and THP1-PMA macrophages caused robust uptake, detected by Ru-NO fluorescence using mass-cytometry, confocal microscopy, and flow cytometry.

Discovery of an ʟ-amino acid ligase implicated in Staphylococcal sulfur amino acid metabolism.

Enzymes involved in Staphylococcus aureus amino acid metabolism have recently gained traction as promising targets for the development of new antibiotics, however, not all aspects of this process are understood. The ATP-grasp superfamily includes enzymes that predominantly catalyze the ATP-dependent ligation of various carboxylate and amine substrates. One subset, ʟ-amino acid ligases (LALs), primarily catalyze the formation of dipeptide products in Gram-positive bacteria, however, their involvement in S.

Don't Turn Off the Tap! The Importance of Discovery Science to the Australian Cardiovascular Sector and Improving Clinical Outcomes Into the Future.

Despite significant advances in interventional and therapeutic approaches, cardiovascular disease (CVD) remains the leading cause of death and mortality. To lower this health burden, cardiovascular discovery scientists need to play an integral part in the solution. Successful clinical translation is achieved when built upon a strong foundational understanding of the disease mechanisms involved.

Vitrification within a nanoliter volume: oocyte and embryo cryopreservation within a 3D photopolymerized device.

Purpose: Vitrification permits long-term banking of oocytes and embryos. It is a technically challenging procedure requiring direct handling and movement of cells between potentially cytotoxic cryoprotectant solutions. Variation in adherence to timing, and ability to trace cells during the procedure, affects survival post-warming.

Designer D-peptides targeting the N-terminal region of α-synuclein to prevent parkinsonian-associated fibrilization and cytotoxicity.

The deposition of α-synuclein (αS) aggregates in the gut and the brain is ever present in cases of Parkinson's disease. While the central non-amyloidogenic-component (NAC) region of αS plays a critical role in fibrilization, recent studies have identified a specific sequence from within the N-terminal region (NTR, residues 36-42) as a key modulator of αS fibrilization. Due to the lack of effective therapeutics which specifically target αS aggregates, we have developed a strategy to prevent the aggregation and subsequent toxicity attributed to αS fibrilization utilizing NTR targeting peptides.