Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment.

Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.

Predictably manipulating photoreceptor light responses to reveal their role in downstream visual responses.

Computation in neural circuits relies on the judicious use of nonlinear circuit components. In many cases, multiple nonlinear components work collectively to control circuit outputs. Separating the contributions of these different components is difficult, and this limits our understanding of the mechanistic basis of many important computations.

Vesicle-based formulations for pain treatment: a narrative review.

Pain, a complex and debilitating condition, necessitates innovative therapeutic strategies to alleviate suffering and enhance patients' quality of life. Vesicular systems hold the potential to enhance precision of drug localisation and release, prolong the duration of therapeutic action and mitigate adverse events associated with long-term pharmacotherapy. This review critically assesses the current state-of-the-art in vesicle-based formulations (liposomes, polymersomes, ethosomes, and niosomes) for pain management applications.

Development and validation of a mouse model to investigate post surgical pain after laparotomy.

Background: Postoperative pain following abdominal surgery is a significant obstacle to patient recovery, often necessitating high analgesic doses associated with adverse effects like cognitive impairment and cardiorespiratory depression. Reliable animal models are crucial for understanding the pathophysiology of post surgical pain and developing more effective pain-relieving strategies.

Methods: We developed a mouse model to replicate peritoneal trauma induced by abdominal surgery.

Implications of the genomic revolution for education research and policy.

Research at the intersection of social science and genomics, 'sociogenomics', is transforming our understanding of the interplay between genomics, individual outcomes and society. It has interesting and maybe unexpected implications for education research and policy. Here we review the growing sociogenomics literature and discuss its implications for educational researchers and policymakers.

Maleimide-Thiol Linkages Alter the Biodistribution of SN38 Therapeutic Microbubbles Compared to Biotin-Avidin While Preserving Parity in Tumoral Drug Delivery.

Therapeutic microbubbles (thMBs) contain drug-filled liposomes linked to microbubbles and targeted to vascular proteins. Upon the application of a destructive ultrasound trigger, drug uptake to tumour is improved. However, the structure of thMBs currently uses powerful non-covalent bonding of biotin with avidin-based proteins to link both the liposome to the microbubble (MB) and to bind the targeting antibody to the liposome-MB complex.

Deep learning for real-time multi-class segmentation of artefacts in lung ultrasound.

Lung ultrasound (LUS) has emerged as a safe and cost-effective modality for assessing lung health, particularly during the COVID-19 pandemic. However, interpreting LUS images remains challenging due to its reliance on artefacts, leading to operator variability and limiting its practical uptake. To address this, we propose a deep learning pipeline for multi-class segmentation of objects (ribs, pleural line) and artefacts (A-lines, B-lines, B-line confluence) in ultrasound images of a lung training phantom.

Predictably manipulating photoreceptor light responses to reveal their role in downstream visual responses.

Computation in neural circuits relies on the judicious use of nonlinear circuit components. In many cases, multiple nonlinear components work collectively to control circuit outputs. Separating the contributions of these different components is difficult, and this limits our understanding of the mechanistic basis of many important computations.

Inhibiting B cell activating factor attenuates preeclamptic symptoms in placental ischemic rats.

Problem: Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with a pro-inflammatory state with activated T cells, cytolytic natural killer (NK) cells, dysregulated complement proteins, and B cells secreting agonistic autoantibodies to the angiotensin II type-1 receptor (AT1-AA). The reduced uterine perfusion pressure (RUPP) model of placental ischemia recapitulates these features of PE. Blocking CD40L-CD40 communication between T and B cells or B cell depletion with Rituximab prevents hypertension and AT1-AA production in RUPP rats.

Tumour associated vasculature-on-a-chip for the evaluation of microbubble-mediated delivery of targeted liposomes.

The vascular system is the primary route for the delivery of therapeutic drugs throughout the body and is an important barrier at the region of disease interest, such as a solid tumour. The development of complex 3D tumour cultures has progressed significantly in recent years however, the generation of perfusable vascularised tumour models still presents many challenges. This study presents a microfluidic-based vasculature system that can be induced to display properties of tumour-associated blood vessels without direct incorporation of tumour cells.

Reprogramming Müller glia to regenerate ganglion-like cells in adult mouse retina with developmental transcription factors.

Many neurodegenerative diseases cause degeneration of specific types of neurons. For example, glaucoma leads to death of retinal ganglion cells, leaving other neurons intact. Neurons are not regenerated in the adult mammalian central nervous system.

B2 cells contribute to hypertension and natural killer cell activation possibly via AT1-AA in response to placental ischemia.

Preeclampsia, new onset hypertension during pregnancy, is associated with activated T helper cells (Th) and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). The reduced uterine perfusion pressure (RUPP) model of placental ischemia recapitulates these characteristics. We have shown that Th-B cell communication contributes to AT1-AA and symptoms of preeclampsia in the RUPP rat.

The Influence of Nanobubble Size and Stability on Ultrasound Enhanced Drug Delivery.

Lipid-shelled nanobubbles (NBs) are emerging as potential dual diagnostic and therapeutic agents. Similar to their micron-scale counterparts, microbubbles (1-10 μm), they can act as ultrasound contrast agents as well as locally enhance therapeutic uptake. Recently, it has been shown that the reduced size of NBs (<1 μm) promotes increased uptake and accumulation in tumor interstitial space, which can enhance their diagnostic and therapeutic performance.

Hyaluronic-Acid-Tagged Cubosomes Deliver Cytotoxics Specifically to CD44-Positive Cancer Cells.

Delivery of chemotherapy drugs specifically to cancer cells raises local drug doses in tumors and therefore kills more cancer cells while reducing side effects in other tissues, thereby improving oncological and quality of life outcomes. Cubosomes, liquid crystalline lipid nanoparticles, are potential vehicles for delivery of chemotherapy drugs, presenting the advantages of biocompatibility, stable encapsulation, and high drug loading of hydrophobic or hydrophilic drugs. However, active targeting of drug-loaded cubosomes to cancer cells, as opposed to passive accumulation, remains relatively underexplored.

A Single Short 'Tone Burst' Results in Optimal Drug Delivery to Tumours Using Ultrasound-Triggered Therapeutic Microbubbles.

Advanced drug delivery systems, such as ultrasound-mediated drug delivery, show great promise for increasing the therapeutic index. Improvements in delivery by altering the ultrasound parameters have been studied heavily in vitro but relatively little in vivo. Here, the same therapeutic microbubble and tumour type are used to determine whether altering ultrasound parameters can improve drug delivery.

Proteolytic pan-RAS Cleavage Leads to Tumor Regression in Patient-derived Pancreatic Cancer Xenografts.

The lack of effective RAS inhibition represents a major unmet medical need in the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, we investigate the anticancer activity of RRSP-DTB, an engineered biologic that cleaves the Switch I of all RAS isoforms, in KRAS-mutant PDAC cell lines and patient-derived xenografts (PDX). We first demonstrate that RRSP-DTB effectively engages RAS and impacts downstream ERK signaling in multiple KRAS-mutant PDAC cell lines inhibiting cell proliferation at picomolar concentrations.

Affimer Tagged Cubosomes: Targeting of Carcinoembryonic Antigen Expressing Colorectal Cancer Cells Using and Models.

Nanomedicines, while having been approved for cancer therapy, present many challenges such as low stability, rapid clearance, and nonspecificity leading to off-target toxicity. Cubosomes are porous lyotropic liquid crystalline nanoparticles that have shown great premise as drug delivery vehicles; however, their behavior is largely underexplored, hindering clinical translation. Here, we have engineered cubosomes based on the space group 3 that are loaded with copper acetylacetonate as a model drug, and their surfaces are functionalized for the first time with Affimer proteins via copper-free click chemistry to actively target overexpressed carcinoembryonic antigens on LS174T colorectal cancer cells.

Evaluation of the Targeting and Therapeutic Efficiency of Anti-EGFR Functionalised Nanoparticles in Head and Neck Cancer Cells for Use in NIR-II Optical Window.

Gold nanoparticles have been indicated for use in a diagnostic and/or therapeutic role in several cancer types. The use of gold nanorods (AuNRs) with a surface plasmon resonance (SPR) in the second near-infrared II (NIR-II) optical window promises deeper anatomical penetration through increased maximum permissible exposure and lower optical attenuation. In this study, the targeting and therapeutic efficiency of anti-epidermal growth factor receptor (EGFR)-antibody-functionalised AuNRs with an SPR at 1064 nm was evaluated in vitro.

Mini-medical school programs decrease perceived barriers of pursuing medical careers among underrepresented minority high school students.

Context: The percent of underrepresented minority (URM) students who apply to medical school has changed minimally in the past 40 years. Due to the lack of URM applicants, the consequent matriculation of URMs is grossly disproportionate from their percent representation of the US population. Increasing diversity among medical students and physicians has previously been identified as essential to decreasing healthcare disparities among US minorities.

Barium and titanium dithiocarbamates as precursors for colloidal nanocrystals of emerging optoelectronic materials.

The synthesis and structures of ,-dialkyldithiocarbamate complexes of barium are reported; the compounds crystallize as one-dimensional coordination polymers. In combination with a titanium dithiocarbamate precursor, the compounds are demonstrated as competent single-source precursors for the solution-based preparation of colloidal BaTiS nanorods.

Not All Piggybacks Are Equal: A Retrospective Cohort Analysis of Variation in Anhepatic Transcaval Pressure Gradient and Acute Kidney Injury During Liver Transplant.

Objectives: Complete inferior vena cava clamping in cavalreplacement during livertransplantis associated with substantial physiological derangement and postoperative morbidity. Partial clamping in the piggyback technique may be relatively protective, but evidence is lacking. Having observed substantial variation in transhepatic inferior vena cava pressure gradient with piggyback, we hypothesized that the causative mechanism is the extent of caval clamping rather than the surgical approach.

Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4.

The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer.

Evaluating Phospholipid-Functionalized Gold Nanorods for In Vivo Applications.

Gold nanorods (AuNRs) have attracted a great deal of attention due to their potential for use in a wide range of biomedical applications. However, their production typically requires the use of the relatively toxic cationic surfactant cetyltrimethylammonium bromide (CTAB) leading to continued demand for protocols to detoxify them for in vivo applications. In this study, a robust and facile protocol for the displacement of CTAB from the surface of AuNRs using phospholipids is presented.

Freeze-Dried Therapeutic Microbubbles: Stability and Gas Exchange.

Microbubbles (MBs) are widely used as contrast enhancement agents for ultrasound imaging and have the potential to enhance therapeutic delivery to diseases such as cancer. Yet, they are only stable in solution for a few hours to days after production, which limits their potential application. Freeze-drying provides long-term storage, ease of transport, and consistency in structure and composition, thereby facilitating their use in clinical settings.