The Receptor for Advanced Glycation End-products (RAGE) has been implicated in driving cancer growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarize and analyze current clinical and preclinical data to provide insight into the relationship between RAGE and cancer, cancer grade, metastasis, patient survival, and cellular processes. A multi-database search was performed to identify original clinical and preclinical research studies examining RAGE expression in cancer. After screening and review, 53 clinical and 233 preclinical studies were included. Associations of RAGE with clinical cancer outcomes were estimated using odds ratio (OR) and associated 95% confidence intervals (CI). The meta-analysis found that RAGE expression was highly correlated with cancerous tissue when compared to controls; high-grade tumors; regional lymph node invasion; and was somewhat negatively associated with patient survival. In addition, meta-analysis estimates of preclinical studies found positive associations between RAGE expression/activation and cancer growth, metastatic potential, evasion of apoptosis, and activated NF-κB expression. This systematic review and meta-analysis is the first comprehensive study through which both preclinical and clinical research in all available cancer types are assessed for correlations with RAGE expression and activation, demonstrating that RAGE does indeed play a significant role in cancer progression and that further research is warranted.

The endothelial tube formation assay is an established in vitro model for evaluating angiogenesis. Although widely used, quantification of angiogenic behavior in such assays remains semi-empirical and often lacks spatial, topological, and structural context. Here, we present a graph-theoretic framework to quantify network morphology, temporal dynamics, and spatial heterogeneity in tube formation assays. We simulated two distinct angiogenic network morphologies using human umbilical vein endothelial cells (HUVECs) seeded at two densities and imaged at 2, 4, and 18 h post-seeding. Skeletonized images were converted to mathematical graphs from which 11 graph-based metrics were extracted. This framework captured both morphological differences and temporal progression. Sparse networks exhibited significantly higher average node degree (p = 0.00079), clustering coefficient (p = 0.00109), and tortuosity (p = 0.0171), whereas dense networks showed greater node and edges counts (p = 0.00109). Over time, networks evolved from fragmented forms at 2 h to integrated structures at 18 h, as reflected by increased largest component size (p = 0.00216), connectivity index (p = 0.00216), and efficiency (p = 0.0152). ROC AUC analysis revealed that metrics such as average degree (AUC = 0.98) and clustering coefficient (AUC = 0.96) effectively distinguished between sparse and dense morphologies, while component-based metrics perfectly separated 2- and 18-hour networks (AUC = 1.00). Radial zone analysis revealed that vascular distribution becomes more compartmentalized over time, with increasing standard deviation and coefficient of variation. This approach provides a sensitive and scalable method for quantifying angiogenic dynamics, offering insight into both therapeutic efficacy and disease-related vascular remodeling.

Excess body fat leads to an overabundance of adipose tissue macrophages (AT MΦs) with altered phenotypes that play pathogenic roles in obesity comorbidities including diabetes and cancer. Peroxisome proliferator-activated receptors (PPARs) are leading targets to modulate AT MΦ phenotype. Here, we developed a dextran-based nanomedicine that delivers PPARα/γ agonists to AT MΦs and improves obesity and diabetic phenotypes in vivo. Within 1 week of treatment, AT MΦs decreased and became lipid laden, while extracellular vesicles secreted from AT decreased and reduced in lipid content. Within 2 weeks, glucose tolerance returned to levels of lean controls, followed by weight loss and reduced food intake. After 4 weeks, AT browning and amelioration of hepatic steatosis were evident. The physiological shifts were reproducible in three rodent models of obesity, spanning sexes and gonadal status. Effects were enhanced for the targeted nanomedicine compared with free drugs at equivalent doses, supporting the hypothesis that targeted PPAR activation in AT MΦs benefits systemic metabolism.

Alteration of blood perfusion leads to some of the most common cardiovascular pathologies. Current methods for measuring perfusion use fluorescent polystyrene microspheres (MS) that are systemically injected prior to processing to obtain the absolute number of MS trapped inside the tissue. The current standard method is cost-intensive and carries a high risk of MS loss, leading to underestimation of regional perfusion. This study aimed to develop an improved, cost-efficient protocol for measuring regional perfusion through the processing and direct imaging of fluorescent MS embedded ex vivo. Porcine and control samples treated with MS were chemically digested, filtered through either a polycarbonate (PCTE) or cellulose filter, and fluorescence was measured either through the standard fluorometric method or through the proposed direct imaging method. In the standard fluorometric method, interactions were found between the PCTE filter and porcine samples, leading to dampened signal and the subsequent underestimation of regional perfusion in practice. The proposed direct imaging method with cellulose filters showed improved sensitivity even within low MS levels (limit of detection improved significantly), amplification of sample fluorescence (11-13× when compared to PCTE filters), parity between porcine and control samples, and a reduction in cost providing a significant improvement over the industry standard for fluorescent MS perfusion measurement (28-51 % reduction compared to standard method). The proposed method also removed the need for 2-ethoxy ethyl acetate, a teratogen and plastic softener, and reduced complexity in the workflow.

PURPOSE:Accurate assessment of intratumoral heterogeneity is critical for tumor characterization and monitoring, but variations in tumor size make it difficult to determine whether radiomic differences reflect true biological heterogeneity or mere volume effects. To address this, we developed Tumor-Volume-Weighted Normalization (TVWN), a framework that minimizes size-related biases while preserving intrinsic image heterogeneity. METHODS:TVWN was evaluated using: (i) computer-simulated tumors (185-800  mm3), (ii) heterogeneous, tumor-mimicking phantoms (10-170  mm3), and (iii) longitudinal PET scans of prostate tumor-bearing mice (35.2-1184  mm3) acquired at four time points. We analyzed 97 radiomic features, including texture metrics from GLRLM and GLSZM, before and after normalization to assess and correct volume dependence. RESULTS:TVWN consistently reduced the influence of tumor volume across various acquisition and reconstruction conditions, including different noise levels, Gaussian filtering (2  mm), number of iterations and spatial resolutions (0-6.0  mm FWHM). For example, the volume dependence ofGlcm_IDNwas effectively reduced (Spearman ρ: 0.290 ± 0.097 to 0.007 ± 0.103 at α = 0.01). In phantom experiments, TVWN reduced the CoV ofGlrlm_REfrom 17.75 % to 3.18 % in filtered data and from 20.14 % to 3.87 % in unfiltered data. It also enhanced heterogeneity discriminability (p = 0.0286). In vivo, TVWN decoupled radiomic features from tumor size progression, ensuring that observed changes reflected biological rather than volumetric effects. CONCLUSION:TVWN offers a simple, scalable approach to normalizing radiomic features against tumor volume effects, improving their reproducibility and biological interpretability in longitudinalstudies.

Peripheral arterial disease (PAD) is a common circulatory condition that leads to reduced blood flow to the limbs, often resulting in limb ischemia which can severely impact a patient's quality of life and increase the risk of amputation. Early diagnosis and timely intervention are critical in managing PAD-associated limb ischemia. This review provides a comprehensive overview of the latest diagnostic and therapeutic approaches for PAD and limb ischemia. We explored both non-invasive and invasive diagnostic techniques including ankle-brachial index, duplex ultrasonography, magnetic resonance angiography, computed tomography angiography and emerging technologies like molecular imaging and near-infrared spectroscopy. Therapeutic strategies discussed include pharmacological treatments such as antiplatelet agents and statins, endovascular interventions like angioplasty and stenting as well as advanced options such as gene and stem cell therapies. Emerging treatments including non-thermal plasma and extracellular vesicle therapy are also highlighted for their regenerative potential. We have also addressed the challenges of current approaches, including diagnostic limitations, barriers to new therapies and cost considerations aimed at improving outcomes for PAD patients.

Understanding the molecular and physical complexity of the tissue microenvironment (TiME) in the context of its spatiotemporal organization has remained an enduring challenge. Recent advances in engineering and data science are now promising the ability to study the structure, functions, and dynamics of the TiME in unprecedented detail; however, many advances still occur in silos that rarely integrate information to study the TiME in its full detail. This review provides an integrative overview of the engineering principles underlying chemical, optical, electrical, mechanical, and computational science to probe, sense, model, and fabricate the TiME. In individual sections, we first summarize the underlying principles, capabilities, and scope of emerging technologies, the breakthrough discoveries enabled by each technology and recent, promising innovations. We provide perspectives on the potential of these advances in answering critical questions about the TiME and its role in various disease and developmental processes. Finally, we present an integrative view that appreciates the major scientific and educational aspects in the study of the TiME.

Nuclear medicine is an important tool for use in molecular imaging of important biological processes. Methods for intravenous delivery of radiotracers remains a challenge, with tail vein injections demonstrated to be technically difficult and lacking in reproducibility. Other intravenous methods include jugular vein (JV) injection, which requires a more invasive and precise microsurgical technique. Although the retroorbital (RO) sinus drains directly into the JV, and RO injections are minimally invasive and simpler to perform, they remain underutilized, perhaps due to a lack of studies demonstrating their performance. This study provides a comprehensive comparison of dynamic tissue biodistribution of three categories of commonly utilized radiopharmaceuticals between JV and RO injection methods in prostate tumor-bearing mice using PET-CT imaging. Results show that JV and RO injections have equivalent dynamic tissue biodistributions across the three categories of radiopharmaceuticals used: (1) small molecule measuring tumor metabolism (18F-flurodeoxyglucose [FDG]); (2) peptide-based probe measuring angiogenesis (64Cu-NOTA-PEG4-cRGD2); and (3) dextran-based nanocarrier (64Cu-NOTA-D20). Although RO injections present with some limitations such as type of injectate and difficulty for measuring acute, dynamic pharmacokinetics, this study demonstrates that RO injections are a viable, minimally invasive or stressful, and efficient alternative intravenous delivery technique for molecular imaging.

Sample multiplexing is an emerging method in single-cell RNA sequencing (scRNA-seq) that addresses high costs and batch effects. Current multiplexing schemes use DNA labels to barcode cell samples but are limited in their stability and extent of labeling of heterogeneous cell populations. Here, we describe nanocoding, a technology that applies lipid nanoparticles (LNPs) for high barcode labeling density in multiplexed scRNA-seq. LNPs reduce dependencies on cell surface labeling mechanisms due to multiple controllable means of cell uptake, amplifying barcode loading 10-100-fold and allowing both protection and efficient release by upon cell lysis. In cultured cell lines and heterogeneous cells from tissue digests, nanocoding occurs in 40 min with stability after sample mixing and requires only commercially available reagents without complex chemical modifications. In spleen digests, 6-plex barcoded samples show minimal unlabeled cells, with all barcodes giving bimodal count distributions. Challenging samples from adipose tissue of obese rodents containing lipid-rich debris and heterogeneous cells show more than 95% labeling with all known subtypes identified. Using nanocoding, we investigate gene expression changes related to aging in adipose tissue, profiling cells that could not be readily identified with current direct conjugate methods using lipid or antibody conjugates. The ease of generating and tuning these constructs may afford efficient and robust sample multiplexing with minimal crosstalk.

Background:Currently available behavioral and dietary weight-loss programs lack magnitude and sustainability compared with bariatric surgery. A novel dietary weight-loss program was developed to assist participants in achieving sustainable diet changes by building knowledge and skills in food self-selection. Although the approach worked, a large variation was observed in outcome among participants. Objective:Determine factors affecting weight-loss outcomes among participants to further improve the efficacy of the program. Methods:Participants attended 19 dietary educational sessions during a 1-year intervention which included prescribed homework. Changes in weight, diet, and body composition were assessed. Results:Participants (n = 22) achieved mean body weight loss of -6.49(8.37%, p < 0.001) from baseline at 12 months. Nine participants (41%) achieved weight loss >5% of initial bodyweight; two reached a Body Mass Index 25 kg/m2. A large divergence in weight loss among participants was observed; successful (n = 9) achieved -12.9(9.6)% while unsuccessful achieved -2.03(2.78)%. Dietary protein and fiber density by 24-h records showed a significant and inverse correlation with weight loss (%) throughout the program. Weight loss at 3 months and 12 months showed a strong correlation (r = 0.84). Participants with self-reported depression lost significantly less weight than those without depression at 12 months (p < 0.03). Conclusions:Divergence in weight-loss outcomes among the participants is likely due to a difference in successful dietary implementation. Intra-cohort analysis indicates early weight-loss success and early dietary implementation was predictive of long-term success.

The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects. A multi-database search was used to identify original clinical and preclinical research articles examining RAGE expression in PCa. After screening and review, nine clinical and six preclinical articles were included. The associations of RAGE differentiating benign prostate hyperplasia (BPH) or normal prostate from PCa and between tumor grades were estimated using odds ratios (ORs) and associated 95% confidence intervals (CI). Pooled estimates were calculated using random-effect models due to study heterogeneity. The clinical meta-analysis found that RAGE expression was highly likely to be increased in PCa when compared to BPH or normal prostate (OR: 11.3; 95% CI: 4.4–29.1) and that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5; 95% CI: 1.8–3.4). In addition, meta-analysis estimates of preclinical studies performed by albatross plot generation found robustly positive associations among RAGE expression/activation and PCa growth and metastatic potential. This review demonstrates that RAGE expression is strongly tied to PCa progression and can serve as an effective diagnostic target to differentiate between healthy prostate, low-grade PCa, and high-grade PCa, with potential theragnostic applications.

Given the dynamic market for protein-based ingredients in the pet food industry, demand continues to increase for both plant- and animal-based options. Protein sources contain different amino acid (AA) profiles and vary in digestibility, affecting protein quality. The objective of this study was to evaluate the apparent total tract digestibility (ATTD) of canine diets differing in protein source and test their effects on serum metabolites and fecal characteristics, metabolites, and microbiota of healthy adult dogs consuming them. Four extruded diets were formulated to be isonitrogenous and meet the nutrient needs for adult dogs at maintenance, with the primary difference being protein source: 1) fresh deboned, dried, and spray-dried chicken (DC), 2) chicken by-product meal (CBPM), 3) wheat gluten meal (WGM), and 4) corn gluten meal (CGM). Twelve adult spayed female beagles (body weight [BW] = 9.9 1.0 kg; age = 6.3 1.1 yr) were used in a replicated 4 x 4 Latin square design (n = 12/treatment). Each period consisted of a 22-d adaptation phase, 5 d for fecal collection, and 1 d for blood collection. Fecal microbiota data were analyzed using QIIME 2.2020.8. All other data were analyzed using the Mixed Models procedure of SAS version 9.4. Fecal scores were higher (P < 0.05; looser stools) in dogs fed DC or CBPM than those fed WGM or CGM, but all remained within an appropriate range. Dry matter ATTD was lower (P < 0.05) in dogs fed CBPM or CGM than those fed DC or WGM. Crude protein ATTD was lower (P < 0.05) in dogs fed DC or CGM than those fed WGM. Dogs fed CBPM had lower (P < 0.05) organic matter, crude protein, and energy ATTD than those fed the other diets. Fecal indole was higher (P < 0.05) in dogs fed CBPM than those fed WGM. Fecal short-chain fatty acids were higher (P < 0.05) in dogs fed DC than those fed CGM. Fecal branched-chain fatty acids were higher (P < 0.05) in dogs fed DC or CBPM than those fed WGM. Fecal ammonia was higher (P < 0.05) in dogs fed DC or CBPM than those fed WGM or CGM. The relative abundances of three bacterial phyla and nine bacterial genera were shifted among treatment groups (P < 0.05). Considering AA profiles and digestibility data, the DC diet protein sources provided the highest quality protein without additional AA supplementation, but the animal-based protein diets resulted in higher fecal proteolytic metabolites. Further studies evaluating moderate dietary protein concentrations are needed to better compare plant- and animal-based protein sources. The current study tested dog diets differing in protein source, including those derived from plants and animals. Dietary differences were noted in nutrient digestibility, fecal metabolites, and fecal microbiota, but gene expression was unaffected. Lay Summary Pet food trends are constantly changing. Because consumers are often focused on dietary proteins, with ingredient sources, dietary inclusion levels, and processing methods being important, they are a popular research topic. Protein sources contain different amino acid (AA) profiles and vary in digestibility, affecting protein quality. Our objective was to evaluate the apparent total tract digestibility of canine diets differing in protein source and test their effects on serum metabolites and fecal characteristics, metabolites, and microbiota of healthy adult dogs. Test diets were formulated to be similar nutritionally, but differed in protein source: fresh deboned, dried, and spray-dried chicken (DC), chicken by-product meal (CBPM), wheat gluten meal (WGM), and corn gluten meal (CGM). Fecal scores were higher in dogs fed chicken-based diets, but remained within an appropriate range. Dogs fed CBPM had lower nutrient and energy digestibilities than those fed the other diets, with protein digestibility also being lower in dogs fed DC or CGM than those fed WGM. Fecal metabolites and microbiota were shifted among diets, with animal-based protein diets increasing fecal protein metabolites. All diets were complete and balanced and performed well. When considering AA profiles and digestibility, however, the DC diet provided the highest protein quality.

The receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory processes. The involvement of RAGE in the pathogenesis of disorders such as diabetes, inflammation, tumor progression, and endothelial dysfunction is dictated by the accumulation of advanced glycation end-products (AGEs) at pathologic states leading to sustained RAGE upregulation. The involvement of RAGE and its ligands in numerous pathologies and diseases makes RAGE an interesting target for therapy focused on the modulation of both RAGE expression or activation and the production or exogenous administration of AGEs. Despite the known role that the RAGE/AGE axis plays in multiple disease states, there remains an urgent need to develop noninvasive, molecular imaging approaches that can accurately quantify RAGE levels in vivo that will aid in the validation of RAGE and its ligands as biomarkers and therapeutic targets. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Diagnostic Tools > Biosensing.

BACKGROUND:High-protein diets not only meet amino acid needs but also modulate satiety and energy metabolism. Insect-based proteins are sustainable, high-quality proteins. Mealworms have been studied, but limited information is known about their ability to impact metabolism and obesity. OBJECTIVE:We determined the effects of defatted yellow mealworm (Tenebrio molitor)- and whole lesser mealworm (Alphitobius diaperinus)-based proteins on the body weight (BW), serum metabolites, and liver and adipose tissue (AT) histology and gene expression of diet-induced obesity mice. METHODS:Male C57BL/6J mice were fed a high-fat diet (HFD; 46% kcal) to induce obesity and metabolic syndrome. Obese mice were then assigned to treatments (n = 10/group) and fed for 8 wk: HFD: HFD with casein protein; B50: HFD with 50% protein from whole lesser mealworm; B100: HFD with 100% protein from whole lesser mealworm; Y50: HFD with 50% protein from defatted yellow mealworm; Y100: HFD with 100% protein from defatted yellow mealworm. Lean mice (n = 10) fed a low-fat-diet (LFD; 10% kcal) were included. Longitudinal food intake, BW, body composition, and glucose response were measured. At time of killing, serum metabolites, tissue histopathology and gene expression, and hepatic triglycerides were analyzed. RESULTS:After 8 wk, HFD, B50, and B100 had greater (P < 0.05) weight gain than LFD, whereas Y50 and Y100 did not. Y50, B100, and Y100 had a lower (P < 0.05) BW change rate than HFD. Mealworm-based diets led to increased (P < 0.05) serum high-density lipoprotein (HDL) and reduced (P < 0.05) serum low-density lipoprotein (LDL) concentrations and reduced (P<0.05) LDL/HDL ratio. Mealworm-based diets led to increased (P < 0.05) hepatic expression of genes related to energy balance, immune response, and antioxidants and reduced (P < 0.05) AT expression of genes associated with inflammation and apoptosis. Mealworm-based diets altered (P < 0.05) hepatic and AT expression of glucose and lipid metabolism genes. CONCLUSIONS:In addition to serving as an alternative protein source, mealworms may confer health benefits to obese patients.

Purported benefits of human-grade pet foods include reduced inflammation, enhanced coat quality, and improved gut health, but research is scarce. Therefore, we compared gene expression, skin and coat health measures, and the fecal microbiome of dogs consuming a mildly cooked human-grade or extruded kibble diet. Twenty beagles (BW = 10.25 +/- 0.82 kg; age = 3.85 +/- 1.84 yr) were used in a completely randomized design. Test diets included: 1) chicken and brown rice recipe [feed-grade; extruded; blue buffalo (BB)]; and 2) chicken and white rice [human-grade; mildly cooked; Just Food for Dogs (JFFD)]. The study consisted of a 4-week baseline when all dogs ate BB, and a 12-week treatment phase when dogs were randomized to either diet (n = 10/group). After the baseline and treatment phases, fresh fecal samples were scored and collected for pH, dry matter (DM), and microbiome analysis; blood samples were collected for gene expression analysis; hair samples were microscopically imaged; and skin was analyzed for delayed-type hypersensitivity (DTH), sebum concentration, hydration status, and transepidermal water loss (TEWL). Data were analyzed as a change from baseline (CFB) using the Mixed Models procedure of SAS (version 9.4). At baseline, fecal pH was higher (P < 0.05) and hair surface score, superoxide dismutase (SOD) expression, and tumor necrosis factor-alpha (TNF-alpha) expression was lower (P < 0.05) in dogs allotted to JFFD. The decrease in CFB fecal pH and DM was greater (P < 0.05) in dogs fed JFFD, but fecal scores were not different. The increase in CFB hair surface score was higher (P < 0.05) in dogs fed JFFD. The decrease in CFB TEWL (back region) was greater (P < 0.05) in dogs fed JFFD, but TEWL (inguinal and ear regions), hydration status, and sebum concentrations in all regions were not different. Hair cortex scores and DTH responses were not affected by diet. The increase in CFB gene expression of SOD, COX-2, and TNF-alpha was greater (P < 0.05) in dogs fed JFFD. PCoA plots based on Bray-Curtis distances of bacterial genera and species showed small shifts over time in dogs fed BB, but dramatic shifts in those fed JFFD. JFFD increased (adj. P < 0.05) relative abundances of 4 bacterial genera, 11 bacterial species, 68 KEGG pathways, and 167 MetaCyc pathways, and decreased (adj. P < 0.05) 16 genera, 25 species, 98 KEGG pathways, and 87 MetaCyc pathways. In conclusion, the JFFD diet dramatically shifted the fecal microbiome but had minor effects on skin and coat measures and gene expression. Lay Summary This study tested the effects of a mildly cooked human-grade diet and a feed-grade extruded kibble diet on the fecal microbiome, skin and coat health measures, and expression of genes related to inflammation and oxidative stress in healthy adult dogs. During a 4-week baseline, 20 beagles consumed the kibble diet. After baseline, 10 dogs continued to consume that diet, while 10 dogs consumed the mildly cooked diet for 12 weeks. After baseline and treatment phases, fresh fecal, blood, and hair samples were collected and skin was analyzed. The mildly cooked diet led to lower fecal pH and dry matter percentage, but fecal scores were not affected. The mildly cooked diet dramatically altered the fecal microbiome, shifting the relative abundances of over 30 bacterial species and 165 bacterial metabolic pathways. Measures of skin sebum content and hydration status were not different between groups, but skin water loss was lower in dogs consuming the mildly cooked diet. Baseline and post-treatment gene expression and hair surface scores were noted, but hair cortex and delayed-type hypersensitivity testing were not altered by diet. Our results demonstrate that mildly cooked diets dramatically change the fecal microbiome, but may not impact skin and coat in healthy adult dogs over a short time period. The current study expanded the research on mildly cooked human-grade dog diets, demonstrating that they dramatically alter the fecal microbiome without changing the fecal scores of healthy adult dogs. While minor differences in blood gene expression and skin and coat health measures were observed after 12 weeks of feeding, our results suggest that improvements would require a longer period of study or testing in animals with lower health status.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Although current diagnostic and disease monitoring tests for IBD sensitively detect gut inflammation, they lack the molecular and cellular specificity of positron emission tomography (PET). In this proof-of-concept study, we use a radiolabeled macrophage-targeted nanocarrier probe (64Cu-NOTA-D500) administered by oral, enema, and intraperitoneal routes to evaluate the delivery route dependence of biodistribution across healthy and diseased tissues in a murine model of dextran sodium sulfate (DSS)-induced colitis. High inter-subject variability of probe uptake in intestinal tissue was reduced by normalization to uptake in liver or total intestines. Differences in normalized uptake between healthy and DSS colitis animal intestines were highest for oral and IP routes. Differences in absolute liver uptake reflected a possible secondary diagnostic metric of IBD pathology. These results should inform the preclinical development of inflammation-targeted contrast agents for IBD and related gut disorders to improve diagnostic accuracy.

Prostate cancer (PCa) remains the second most diagnosed cancer worldwide. Higher body weight is associated with chronic inflammation, increased angiogenesis, and treatment-resistant tumor phenotypes. Dietary tomato reduces PCa risk, which may be due to tomato inhibition of angiogenesis and disruption of androgen signaling. This pilot study investigated the interplay between tomato powder (TP), incorporated into control (CON) and obesogenic (OB) diets, and PCa tumor growth and blood perfusion over time in a transgenic model of PCa (TRAMP). Ultrasound microvessel imaging (UMI) results showed good agreement with gold-standard immunohistochemistry quantification of endothelial cell density, indicating that this technique can be applied to non-invasively monitor tumor blood perfusion in vivo. Greater body weight was positively associated with tumor growth. We also found that TP significantly inhibited prostate tumor angiogenesis but that this inhibition differentially affected measured outcomes depending on CON or OB diets. TP led to reduced tumor growth, intratumoral inflammation, and intratumoral androgen-regulated gene expression (srd5a1, srd5a2) when incorporated with the CON diet but greater tumor growth and intratumoral gene expression when incorporated with the OB diet. Results from this study show that protective benefits from dietary tomato are lost, or may become deleterious, when combined with a Western-style diet.