One step 4× and 12× 3D-ExM enables robust super-resolution microscopy of nanoscale cellular structures.

Super-resolution microscopy has become an indispensable tool across diverse research fields, offering unprecedented insights into biological architectures with nanometer scale resolution. Compared with traditional nanometer-scale imaging methods such as electron microscopy, super-resolution microscopy offers several advantages, including the simultaneous labeling of multiple target biomolecules with high specificity and simpler sample preparation, making it accessible to most researchers. In this study, we introduce two optimized methods of super-resolution imaging: 4-fold and 12-fold 3D-isotropic and preserved Expansion Microscopy (4× and 12× 3D-ExM).

Advances in Microengineered Platforms for Skin Research.

The skin plays a critical role in human physiology, acting both as a barrier to environmental insults and as a window to environmental stimuli. Disruption of this homeostasis leads to numerous skin disorders. Human and animal skin differ significantly, limiting the translational potential of animal-based investigations to advance therapeutics to human skin diseases.

Harnessing the regenerative potential of interleukin11 to enhance heart repair.

Balancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. The role of Interleukin 11 (IL11) in heart regeneration remains controversial, as both regenerative and fibrotic functions have been reported. We uncovered that il11a, an Il11 homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury.

Evaluation of a mucoadhesive auto-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

This study investigated the potential of self-nanoemulsifying drug delivery systems (SNEDDS) to optimize the oral bioavailability of insulin. Insulin complexes with phospholipids and enzymatically-modified phospholipids were developed and incorporated into the SNEDDS using Lauroglycol FCC as the oily phase and Cremophor EL and Labrafil M1944CS as the surfactant and co-surfactant, respectively. Additionally, mucoadhesive polysaccharides (sodium alginate and guar gum) were added further to enhance the bioavailability of insulin in these systems.

CCL21 Induces Plasmacytoid Dendritic Cell Migration and Activation in a Mouse Model of Glioblastoma.

Dendritic cells (DCs) are professional antigen-presenting cells that are traditionally divided into two distinct subsets: myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). pDCs are known for their ability to secrete large amounts of cytokine type I interferons (IFN- α). In our previous work, we have demonstrated that pDC infiltration promotes glioblastoma (GBM) tumor immunosuppression through decreased IFN-α secretion via TLR-9 signaling and increased suppressive function of regulatory T cells (Tregs) via increased IL-10 secretion, resulting in poor overall outcomes in mouse models of GBM.

Metabolic modulation of melanoma enhances the therapeutic potential of immune checkpoint inhibitors.

Introduction: Lactate is a pivotal molecule with diverse functions in the metabolic reprogramming of cancer cells. Beyond its role in metabolism, lactate exerts a modulatory effect within the tumor microenvironment; it is utilized by stromal cells and has been implicated in the suppression of the immune response against the tumor.

Methods: Using assays (including flow cytometry, live-cell imaging and metabolic analyses), the impact of lactate dehydrogenase inhibitors (LDHIs) on melanoma cells were assessed.

Data mining of PubChem bioassay records reveals diverse OXPHOS inhibitory chemotypes as potential therapeutic agents against ovarian cancer.

Focused screening on target-prioritized compound sets can be an efficient alternative to high throughput screening (HTS). For most biomolecular targets, compound prioritization models depend on prior screening data or a target structure. For phenotypic or multi-protein pathway targets, it may not be clear which public assay records provide relevant data.

Transcriptomic and proteomic spatial profiling of pediatric and adult diffuse midline glioma H3 K27-Altered.

Diffuse midline glioma, H3 K27-altered (DMG) are highly aggressive malignancies of the central nervous system (CNS) that primarily affect the pediatric population. Large scale spatial transcriptomic studies have implicated that tumor microenvironmental landscape plays an important role in determining the phenotypic differences in tumor presentation and clinical course, however, data connecting overall transcriptomic changes to the protein level is lacking. The NanoString GeoMx Digital Spatial Profiler platform was used to determine the spatial transcriptomic and proteomic landscape in a cohort of both pediatric and adult H3 K27-altered DMG biopsy samples.

One step 4x and 12x 3D-ExM: robust super-resolution microscopy in cell biology.

Super-resolution microscopy has become an indispensable tool across diverse research fields, offering unprecedented insights into biological architectures with nanometer scale resolution. Compared to traditional nanometer-scale imaging methods such as electron microscopy, super-resolution microscopy offers several advantages, including the simultaneous labeling of multiple target biomolecules with high specificity and simpler sample preparation, making it accessible to most researchers. In this study, we introduce two optimized methods of super-resolution imaging: 4-fold and 12-fold 3D-isotropic and preserved Expansion Microscopy (4x and 12x 3D-ExM).

Development of non-sedating benzodiazepines with antischistosomal activity.

The neglected tropical disease schistosomiasis infects over 200 million people worldwide and is treated with just one broad-spectrum antiparasitic drug (praziquantel). Alternative drugs are needed in the event of emerging praziquantel resistance or treatment failure. One promising lead that has shown efficacy in animal models and a human clinical trial is the benzodiazepine meclonazepam, discovered by Roche in the 1970s.

Protein Arginine Methyltransferase CARM1 in Human Breast Cancer.

Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that deposits asymmetrical dimethylation marks on both histone and nonhistone substrates. The regulatory role of CARM1 in transcription was first identified in estrogen receptor positive (ER+) breast cancer. Since then, the mechanism of CARM1 in activating ER-target genes has been further interrogated.

Maintenance low-dose fixed duration lenalidomide and rituximab following bendamustine and rituximab induction in previously untreated chronic lymphocytic leukemia and small lymphocytic lymphoma.

Lenalidomide (LEN) and rituximab (RTX) have independently improved progression-free survival (PFS) in CLL, leading to interest in use of LEN + RTX (R2) following induction chemoimmunotherapy. Patients with previously untreated CLL received bendamustine + RTX (BR) for 6 cycles, then 24 cycles of R2. LEN dosing was 5-10 mg daily; RTX was given odd cycles (12 doses).

Sequence of androgen receptor-targeted vaccination with androgen deprivation therapy affects anti-prostate tumor efficacy.

Rationale: Androgen deprivation therapy (ADT) is the primary treatment for recurrent and metastatic prostate cancer. In addition to direct antitumor effects, ADT has immunomodulatory effects such as promoting T-cell infiltration and enhancing antigen processing/presentation. Previous studies in our laboratory have demonstrated that ADT also leads to increased expression of the androgen receptor (AR) and increased recognition of prostate tumor cells by AR-specific CD8+T cells.

Integration of a clinical pharmacist practitioner-led pharmacogenomics service in a Veterans Affairs hematology/oncology clinic.

Purpose: This article describes the implementation and evaluation of pharmacogenomic testing within the hematology/oncology ambulatory care clinic at the William S. Middleton Memorial Veterans Hospital in Madison, WI.

Summary: The Pharmacogenomic Testing for Veterans (PHASER) program provides preemptive pharmacogenomic testing for veterans nationally.

An algorithm for standardization of tumor Infiltrating lymphocyte evaluation in head and neck cancers.

Purpose: The prognostic and predictive significance of pathologist-read tumor infiltrating lymphocytes (TILs) in head and neck cancers have been demonstrated through multiple studies over the years. TILs have not been broadly adopted clinically, perhaps due to substantial inter-observer variability. In this study, we developed a machine-based algorithm for TIL evaluation in head and neck cancers and validated its prognostic value in independent cohorts.

Heterotopic Auxiliary Whole Liver Rat Transplant Model Utilizing a Hepaticoureterostomy for Allograft Rejection Studies.

Small animal transplant models are indispensable for organ tolerance studies investigating feasible therapeutic interventions in preclinical studies. Rat liver transplantation (LTx) protocols typically use an orthotopic model where the recipients' native liver is removed and replaced with a donor liver. This technically demanding surgical procedure requires advanced micro-surgical skills and is further complicated by lengthy anhepatic and lower body ischemia times.

The reckoning of chromosomal instability: past, present, future.

Quantitative measures of CIN are crucial to our understanding of its role in cancer. Technological advances have changed the way CIN is quantified, offering increased accuracy and insight. Here, we review measures of CIN through its rise as a field, discuss considerations for its measurement, and look forward to future quantification of CIN.

Harnessing the regenerative potential of to enhance heart repair.

Balancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. While Interleukin11 (IL11) is known as a fibrotic factor, its contribution to heart regeneration is poorly understood. We uncovered that homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury.

The CXCL16-CXCR6 axis in glioblastoma modulates T-cell activity in a spatiotemporal context.

Introduction: Glioblastoma multiforme (GBM) pathobiology is characterized by its significant induction of immunosuppression within the tumor microenvironment, predominantly mediated by immunosuppressive tumor-associated myeloid cells (TAMCs). Myeloid cells play a pivotal role in shaping the GBM microenvironment and influencing immune responses, with direct interactions with effector immune cells critically impacting these processes.

Methods: Our study investigates the role of the CXCR6/CXCL16 axis in T-cell myeloid interactions within GBM tissues.

Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients - A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia.

Purpose: Salivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown.

biosynthetic gene cluster diversity highlights the need for broad-spectrum investigations.

Investigations of the bacterial family have enabled the development of secondary metabolites critical to human health. Historical investigation of bacterial families for natural product discovery has focused on terrestrial strains, where time-consuming isolation processes often lead to the rediscovery of known compounds. To investigate the secondary metabolite potential of marine-derived , 38 strains were sequenced, assembled and analysed using antiSMASH and BiG-SLiCE.

Development of Phenyl-substituted Isoindolinone- and Benzimidazole-type Cereblon Ligands for Targeted Protein Degradation.

Thalidomide, pomalidomide and lenalidomide, collectively referred to as immunomodulatory imide drugs (IMiDs), are frequently employed in proteolysis-targeting chimeras (PROTACs) as cereblon (CRBN) E3 ligase-recruiting ligands. However, their molecular glue properties that co-opt the CRL4 to degrade its non-natural substrates may lead to undesired off-target effects for the IMiD-based PROTAC degraders. Herein, we reported a small library of potent and cell-permeable CRBN ligands, which exert high selectivity over the well-known CRBN neo-substrates of IMiDs by structure-based design.

Spatial transcriptomics in glioblastoma: is knowing the right zip code the key to the next therapeutic breakthrough?

Spatial transcriptomics, the technology of visualizing cellular gene expression landscape in a cells native tissue location, has emerged as a powerful tool that allows us to address scientific questions that were elusive just a few years ago. This technological advance is a decisive jump in the technological evolution that is revolutionizing studies of tissue structure and function in health and disease through the introduction of an entirely new dimension of data, spatial context. Perhaps the organ within the body that relies most on spatial organization is the brain.