Translational Research Research Articles

Optimizing orthobiologic therapies with exercise, diet, and supplements.

Orthobiologic injections including platelet-rich plasma (PRP) and cell-based injections are becoming increasingly popular. Evidence suggests that these therapies can be effective in certain situations. The efficacy of these injections may be more dependent on the quality of the injectate, which given their autologous nature, may be dependent on lifestyle choices like exercise, diet, and supplements. The literature describing PRP injections shows that the number and activity of platelets can improve their efficacy. A multitude of lifestyle modifications can affect those factors. Exercise intensity appears to increase platelet count and increases adhesion as well as release of growth factors. Low inflammatory diets increase platelet counts and activity overall. Stress, some supplements, high cholesterol, or processed sugar diets can increase inflammation and potentially decrease platelet counts as well as quality of PRP injectate. Similarly, cell-based therapies can be affected by mesenchymal stromal cell (MSC) number and quality. Cell-based therapy is based upon limiting cellular senescence and increasing replication and differentiation. Exercise may limit senescence and improve replication and differentiation of these cell-based therapies, especially in older adult populations. There are a multitude of supplements that may potentiate these types of injections and patients should discuss the potential benefits and concerns when starting a supplement regimen. Certain foods as well as changes in oxygenation may limit cellular senescence and lower calorie intake may affect MSC viability and function as well. Overall, the current state of literature describes biologic plausibility of how exercise, diet and supplements might affect orthobiologic injection efficacy. Further translational research needs to be completed to describe the effect size and improve recommendations for clinical implementation.

WWC proteins-mediated compensatory mechanism restricts schwannomatosis driven by NF2 loss of function.

NF2-related schwannomatosis, previously known as neurofibromatosis type 2, is a genetic disorder characterized by nerve tumors due to NF2 gene mutations. Mice with Nf2 deletion develop schwannomas slowly with low penetrance, hence inconvenient for preclinical studies. Here, we show that NF2, by recruiting E3 ubiquitin ligases β-TrCP1/2, promotes WWC1-3 ubiquitination and degradation. In NF2 mutated cells, WWC1-3 accumulation is a compensatory mechanism to prevent YAP/TAZ hyperactivation and rapid tumorigenesis. Accordingly, we generate a synthetic mouse model with complete penetrance and short latency by concurrently deleting Nf2 and Wwc1/2 in Schwann cells. This model closely resembles NF2-related schwannomatosis in patients, as confirmed by histological and single-cell transcriptome analysis. Moreover, a cell line from mouse schwannomas and a syngeneic tumor model in immune-competent mice are established. Furthermore, a screen using established models has identified candidate drugs that effectively suppress schwannoma progression. Hence, this work has developed rapid and transplantable models that will facilitate both basic and translational research on NF2-related schwannomatosis.

Patient-derived xenograft models of gastrointestinal stromal tumors: a ready-to-use platform for translational research.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal malignancy of the gastrointestinal tract. Most GIST harbor mutations in oncogenes, such as KIT, and are treated with tyrosine kinase inhibitors (TKI), such as imatinib. Most tumors develop secondary mutations inducing drug resistance against the available TKI, which requires novel therapies. We established a GIST patient-derived xenograft (PDX) platform of GIST that can be used for preclinical drug testing. Tumor tissue from consenting GIST patients was transplanted subcutaneously to NMRI nu/nu mice. Once tumor growth was observed, the tumor was re-transplanted to a next generation of mice. Tumors were characterized histopathologically and molecularly at every re-transplantation and compared with the original patient tumor. We transplanted 112 tumor samples from 99 GIST patients, resulting in 12 established and well-characterized GIST models with different mutations and TKI sensitivity. Three models harbor secondary KIT mutations. One model is characterized by a primary, imatinib-resistant PDGFRA exon 18 p.D842V mutation. Our established platform of well-characterized GIST PDX models, covering the most relevant driver mutations, serves as an excellent tool for preclinical drug testing and tumor biology studies.

A xenogenic-free culture medium for cell micro-patterning systems as cell-instructive biomaterials for potential clinical applications

Cell micro-patterning controls cell fate and function and has potential for generating therapeutically usable mesenchymal stromal cell (MSC) populations with precise functions. However, to date, the micro-patterning of human cells in a translational context has been impossible because only ruminant media supplements, e.g. fetal bovine serum (FBS), are established for use with micro-patterns (MPs). Thus, there are currently no good manufacturing practice (GMP)-compliant media available for MPs. This study tested a xenogenic-free human plasma and platelet lysate (hP + PL) medium supplement to determine its compatibility with MPs. Unfiltered hP + PL medium resulted in significant protein deposition, creating a 'carpet-like' layer that rendered MPs ineffective. Filtration (3×/5×) eliminated this effect. Importantly, quantitative comparison using droplet digital PCR revealed that human MSCs in all media types exhibited similar profiles with strong myogenic Calponin 1/Transgelin 2 (TAGLN2) and weaker osteogenic alkaline phosphatase/Runt-related transcription factor 2 marker expression, and much weaker adipogenic (lipoprotein lipase/peroxisome proliferator-activated receptor gamma) and chondrogenic (collagen type II/aggrecan) expression, with profiles being dominated by myogenic markers. Within these similar profiles, an even stronger induction of the myogenic marker TAGLN2 by all hP + PL- compared to FBS-containing media. Overall, this suggested that FBS can be replaced with hP + PL without altering differentiation profiles. However, assessing individual MSC responses to various MP types with defined categories revealed that unfiltered hP + PL medium was unusable. Importantly, FBS- and 3× filtered hP + PL media were comparable in each differentiation category. Summarized, this study recommends 3× filtered hP + PL as a xenogenic-free and potentially GMP-compliant alternative to FBS as a culture medium supplement for micro-patterning cell populations in both basic and translational research that will ensure consistent and reliable MSC micro-patterning for therapeutic use.

Stipulations of cell and gene therapy and the ties to biomanufacturing.

Cell and gene therapy (CGT) products are emerging and innovative biopharmaceuticals that hold promise for treating diseases that are otherwise beyond the scope of conventional medicines. The evolution of CGT from a research idea to a promising therapeutic product is due to the complementary advancements across various scientific disciplines. First, the innovations and advancements in gene editing and delivery technology have provided fundamental tools to manipulate genes and cells for therapeutic pursuits. Second, advancements in applied and translational research, including how clinical trials are designed, performed, evaluated, and analyzed, have transformed the technology into a potential therapeutic product. Third, advancements in scaling up the production of CGT products have been critical in delivering the product for preclinical studies, clinical trials, and approved treatments. In parallel, regulatory requirements have continuously evolved, with lessons learned from translational studies and biomanufacturing. These combined efforts have transformed CGT products from a promising concept into a reality with the potential to treat a wide range of diseases. However, continued R&D and regulatory oversight are crucial to further improve the safety, efficacy, and accessibility of CGT products.

Breaking barriers in targeted Therapy: Advancing exosome Isolation, Engineering, and imaging.

Exosomes have emerged as promising tools for targeted drug delivery in biomedical applications and medicine. This review delves into the scientific advancements, challenges, and future prospects specifically associated with these technologies. In this work, we trace the research milestones that led to the discovery and characterization of exosomes and extracellular vesicles, and discuss strategies for optimizing the synthetic yield and the loading of these particles with various therapeutics. In addition, we report the current major issues affecting the field and hampering the clinical translation of these technologies. Highlighting the pivotal role of imaging techniques, we explore how they drive exosome therapy and development by offering insights into biodistribution and cellular trafficking dynamics. Methodologies for vesicle isolation, characterization, loading, and delivery mechanisms are thoroughly examined, alongside strategies aimed at enhancing their therapeutic efficacy. Special emphasis was dedicated to their therapeutic properties, particularly to their ability to deliver biologics into the cytoplasm. Furthermore, we delve into the intricate balance between surface modifications and targeting properties including also transgenic methods aimed at their functionalization and visualization within biological systems. This review underscores the transformative potential of these carriers in targeted drug delivery and identifies crucial areas for further research and clinical translation.

Depot-specific adiposity changes in ovariectomized mice on high-fat diet.

Ovariectomized (OVX) mice serve as a key model for studying postmenopausal metabolic changes, particularly obesity, as they mimic the hormonal state of postmenopausal women. However, our understanding remains limited regarding how hormonal and dietary factors affect different adipose tissues. Furthermore, precise documentation of experimental procedures and their effects on specific adipose tissue depots is essential for reproducible translational research. This study investigated depot-specific adiposity development in OVX mice fed a high-fat diet (HFD), focusing on how reduced estrogen levels and dietary intervention affect distinct fat depots. We composed subcutaneous and visceral white adipose tissue (WAT) depots from sham-operated (Sham) and OVX female C57BL/6JJcl mice on a regular diet (RD) and high-fat diet (HFD) for 20 weeks. OVX mice on HFD gained significantly more weight than Sham controls. Adiposity increased in abdominal subcutaneous WAT (sWAT) and perirenal WAT (prWAT) of OVX mice, but not in mesenteric WAT (mWAT). Analysis of adipose tissue morphology revealed that OVX mice exhibited enlarged adipocyte cross-sectional areas under low estrogen (E2) conditions, suggesting enhanced adipogenesis in an estrogen-deficient state. These findings suggest that low estrogen condition accelerated adiposity, in a tissue site-dependent manner.

Our Future Health: a unique global resource for discovery and translational research.

Our Future Health: a unique global resource for discovery and translational research.

Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: apreconception and longitudinal cohort study.

Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes. Quantification of apolipoproteins was performed on maternal plasma samples (N=243 trios) collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Linear regression models and network analysis were implemented to investigate the association of apolipoproteins with maternal genetic variants, biochemical measures, metabolic risk factors, and offspring birth outcomes. The concentrations of ApoC-III, ApoB and ApoL1 substantially increased in pregnancy compared to preconception and postpartum. Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) associated with plasma apolipoproteins (P<5.00E-08), including APOE-rs7412 for ApoE, LPA-rs56393506 for Apo(a), APOM-rs707921 for ApoM, ABCC4-rs117797426 for ApoJ, THSD7B-rs575613 for ApoA-II, and LOC102724443-rs140433245 for ApoA-IV. Plasma apolipoproteins were strongly associated with biochemical measures including lipidomic profiles, lipoprotein features and fat-soluble vitamins, as well as metabolic risk factors including glycaemic traits, liver enzymes, inflammatory markers, albumin, and blood pressure. Integrative network analysis of apolipoproteins and their correlates/determinants revealed both shared and specific associations, with the strongest relationships observed among apolipoproteins, cholesterol, triglycerides, alpha tocopherol, and GlycA (Padj<0.05). Higher maternal ApoC-I and ApoC-III concentrations at preconception were significantly associated with shorter gestational age of the offspring. We describe the longitudinal landscape of maternal circulating apolipoproteins from preconception to postpartum and their associations with maternal metabolic risk factors and offspring birth outcomes. This multi-omics characterisation of biochemical correlates and genetic determinants of maternal apolipoproteins will deepen our understanding of the molecular basis of metabolic flexibility in expectant mothers, leading to better assessment of pregnancy-related outcomes. This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. The Singapore Lipidomics Incubator (SLING) is supported by grants from the National University of Singapore via the Life Sciences Institute, the National Research Foundation (NRF, NRFI2015-05 and NRFSBP-P4) and A∗STAR IAF-ICP I1901E0040. Additional funding is provided by Institute for Human Development and Potential (IHDP)-Agency for Science, Technology and Research (A∗STAR), Singapore.

Guided Multispectral Optoacoustic Tomography for 3D Imaging of the Murine Colon.

Multispectral optoacoustic tomography is a promising medical imaging modality that combines light and sound to provide molecular imaging information at depths of several centimeters, based on the optical absorption of endogenous chromophores, such as hemoglobin. Assessment of inflammatory bowel disease has emerged as a promising clinical application of optoacoustic tomography. In this context, preclinical studies in animal models are essential to identify novel disease-specific imaging biomarkers and understand findings from emerging clinical pilot studies, however to-date, these studies have been limited by the precise identification of the bowel wall. Herein, a transrectal-absorber guide is applied, serving as a high-contrast landmark for 3D optoacoustic tomography of the colon. This study shows that guided multispectral optoacoustic tomography is able to measure changes in blood oxygenation status over the course of acute, chemically-induced colitis in mice and correlates with standard disease activity scores. This novel approach depicts intestinal hemoglobin composition non-invasively during murine inflammation. These results underscore the potential for optoacoustic imaging in translational inflammatory bowel disease research.

Operationalising routinely collected patient data in research to further the pursuit of social justice and health equity: a team-based scoping review

BackgroundVast volumes of routinely collected data (RCD) about patients are collated by health professionals. Leveraging this data – a form of real-world data - can be valuable for quality improvement and contributing to the evidence-base to inform practice. Examining routine data may be especially useful for examining issues related to social justice such as health inequities. However, little is known about the extent to which RCD is utilised in health fields and published for wider dissemination.ObjectivesThe objective of this scoping review is to document the peer-reviewed published research in allied health fields which utilise RCD and evaluate the extent to which these studies have addressed issues pertaining to social justice.MethodsAn enhanced version of the Arksey and O’Malley’s framework, put forth by Westphalm et al. guided the scoping review. A comprehensive literature search of three databases identified 1584 articles. Application of inclusion and exclusion criteria was piloted on 5% of the papers by three researchers. All titles and abstracts were screened independently by 2 team members, as were full texts. A data charting framework, developed to address the research questions, was piloted by three researchers with data extraction being completed by the lead researcher. A sample of papers were independently charted by a second researcher for reliability checking.ResultsOne hundred and ninety papers were included in the review. The literature was diverse in terms of the professions that were represented: physiotherapy (33.7%) and psychology/mental health professions (15.8%) predominated. Many studies were first authored by clinicians (44.2%), often with clinical-academic teams. Some (33.25%) directly referenced the use of their studies to examine translation of research to practice. Few studies (14.2%) specifically tackled issues pertaining to social justice, though many collected variables that could have been utilised for this purpose.ConclusionStudies operationalising RCD can meaningfully address research to practice gaps and provide new evidence about issues related to social justice. However, RCD is underutilised for these purposes. Given that vast volumes of relevant data are routinely collected, more needs to be done to leverage it, which would be supported by greater acknowledgement of the value of RCD studies.

Primary versus Secondary Immune Thrombocytopenia (ITP): A Meeting Report from the 2023 McMaster ITP Summit.

The McMaster Immune Thrombocytopenia (ITP) Summit, held on October 27, 2023, was an educational seminar from leading experts in immune thrombocytopenia and related disorders geared toward hematologists, internists, immunologists, and clinical and translational scientists. The focus of the Summit was to review the mechanisms, diagnosis, and treatment of primary versus secondary ITP. Specific objectives were to describe the unique features of secondary ITP, and to review its mechanisms in the context of autoimmune disease and infection. The key messages in this Summit were: (1) ITP is a heterogeneous disease, and genetic and immunologic insights may help classify patient subtypes; (2) exploring the autoimmune mechanisms and their association with hypogammaglobulinemia in patients with secondary ITP could improve our understanding of ITP and its subtypes; (3) investigating the mechanisms of ITP in the context of infections caused by viruses such as CMV, HIV, dengue, and hepatitis C, or bacteria such as H. pylori, or vaccinations could provide insight into the causes of ITP. A better understanding of secondary ITP could help elucidate the pathogenesis of ITP.

Potential role of formononetin as a novel natural agent in Alzheimer's disease and osteoporosis comorbidity.

The growing aging population has led to an increase in the prevalence of Alzheimer's disease (AD) and osteoporosis (OP), both of which significantly impair quality of life. The comorbid nature of these conditions suggests a shared genetic etiology, the understanding of which is crucial for developing targeted therapies. This study aims to explore the shared genetic etiology underlying AD and OP, using a system biology approach to identify potential therapeutic targets and natural compounds for treatment. We employed Weighted Gene Co-Expression Network Analysis (WGCNA) with molecular docking strategies to uncover the genetic links between AD and OP. MT2A and CACNA1C were identified as key pleiotropic hub genes potentially linking AD and OP. Molecular docking was utilized to screen for compounds with therapeutic potential, leading to the identification of formononetin as a compound with significant binding affinity to these hub genes. Quantitative real-time PCR (qRT-PCR) validation was conducted to confirm the gene expression changes in disease models. Our study indicate that formononetin exhibits strong binding affinity to the identified hub genes, MT2A and CACNA1C. qRT-PCR validation confirmed the upregulation of these genes in disease models, which was mitigated upon treatment with formononetin, suggesting a reversal of disease markers. This study advances our understanding of the genetic intersections between AD and OP and positions formononetin as a promising natural agent for further translational research. Formononetin's multi-target potential makes it a valuable candidate for managing these comorbid conditions, meriting further investigation and development as a therapeutic strategy.

Recent advances in isolation, structures, and bioactivities of Ficus carica L. polysaccharides: A review.

Ficus carica (F. carica) is a well-known medicinal and edible plant with high nutritive values. Polysaccharides are the primary and important bioactive components in F. carica, offering various health benefits. Recently, F. carica polysaccharides (FCPs) have attracted considerable attention due to their various activities, such as anti-oxidant, immunomodulatory, anti-tumor, and anti-diabetic properties. Despite advances in the isolation and characterization of FCPs, critical gaps remain in understanding their structure-activity relationships (SARs), safety concerns, and applications, hindering their full utilization and development. Therefore, a comprehensive review of the latest developments in FCPs is of great significance. Herein, we reviewed the extraction and purification methods, structural characterization, biological activities, SARs, safety concerns, and applications of FCPs. FCPs are water-soluble polysaccharides with molecular weights (Mw) ranging from 21.9 to 6890kDa, primarily composed of glucose, galactose, arabinose, rhamnose, mannose, and xylose. Factors such as the Mw, monosaccharide composition, and extraction methods are crucial in pharmacological activities. Additionally, current challenges and prospects of FCPs are discussed, aiming to provide valuable insights for future research and clinical translation. In conclusion, this article provides insights and foundational knowledge for further research aimed at applying the therapeutic and multifunctional biomaterial properties of FCPs.

How does oxytocin modulate human behavior?

While the highly evolutionarily conserved hypothalamic neuropeptide, oxytocin (OT) can influence cognitive, emotional and social functions, and may have therapeutic potential in disorders with social dysfunction, it is still unclear how it acts. Here, we review the most established findings in both animal model and human studies regarding stimuli which evoke OT release, its primary functional effects and the mechanisms whereby exogenous administration influences brain and behavior. We also review progress on whether OT administration can improve social symptoms in autism spectrum disorder and schizophrenia and consider possible impediments to translational success. Importantly, we emphasize that OT acting via its extensive central or peripheral receptors primarily influences behavior indirectly through neuromodulatory interactions with classical transmitters and other peptides which themselves can independently influence behavior. We also emphasize that exogenous administration studies increasingly demonstrate peripheral effects of OT may be of greater importance than originally thought, especially involving the vagus. Overall, we propose a hierarchical model whereby OT's neuromodulatory actions influence behavior across interconnected functional domains and ultimately help to promote survival, security and sociability. Initially, OT potently facilitates attention to salient social and other important stimuli and additionally modulates cognitive, emotional and reward processing in a person- and context-dependent manner to promote interpersonal social understanding, attraction and bonds on the one hand and social group cohesion through increased conformity, altruistic punishment and moral emotions on the other. OT also increases co-operation and protection across both social domains. We hope this review and model will promote further research and help aid future translation success.

Evolving Paradigms in the Treatment of Oligometastatic Pancreatic Ductal Adenocarcinoma.

Multiple randomized trials have suggested that the addition of comprehensive metastasis-directed therapy to best systemic therapy improves disease control and survival among patients with oligometastatic disease, even for histologies with a high propensity for rapid spread. Here, we review the growing literature supporting the oligometastatic paradigm in pancreatic ductal adenocarcinoma. We summarize key details from nascent institutional series and reflect on the recently reported phase II randomized EXTEND trial. We discuss various strategies for enhancing the clinical and technical implementation of metastasis-directed therapy in this patient population. Lastly, we highlight multiple ongoing landmark trials seeking to optimize and validate the role of metastasis-directed therapy in oligometastatic pancreatic cancer. Ultimately, these and other continued clinical and translational research efforts will be critical to improve care and outcomes for patients with oligometastatic pancreatic ductal adenocarcinoma.

Pharmacogenomic curriculum in Australian medical schools: a content analysis study.

To ascertain and describe pharmacogenomic concepts included in the intended curriculum of accredited Australian medical schools. Content analysis of curriculum learning objectives of Australian medical schools was conducted, focusing on keywords and phrases pertaining to pharmacogenomic education. Learning objectives related to pharmacogenomics were categorized using (1) undergraduate medical genomic competencies per the Association of Professors in Human and Medical Genetics (2) Bloom's Taxonomy for cognitive and knowledge dimensions and (3) knowledge translation (enabling science, translation science and clinical implementation). The curricula of 19 accredited medical schools in Australia were analyzed. Two-thirds (68%) contained genomic/pharmacogenomic education. Eight schools had content relating to undergraduate medical genomic competencies. Of those which had pharmacogenomic-related learning objectives, the majority (65%) were categorized in Bloom's Taxonomy's lower levels (Remember and Understand) and 15% were deemed to be at the level of 'Clinical Implementation.' The majority of Australian medical schools have incorporated pharmacogenomics in their current curriculum; however, learning objectives addressing application and clinical implementation are required. Doctors have a unique role to play in implementing pharmacogenomics into clinical practice. Comprehensiveness of course curricula across all learning domains would support uptake of pharmacogenomics into routine practice.

CausalXtract, a flexible pipeline to extract causal effects from live-cell time-lapse imaging data.

Live-cell microscopy routinely provides massive amounts of time-lapse images of complex cellular systems under various physiological or therapeutic conditions. However, this wealth of data remains difficult to interpret in terms of causal effects. Here, we describe CausalXtract, a flexible computational pipeline that discovers causal and possibly time-lagged effects from morphodynamic features and cell-cell interactions in live-cell imaging data. CausalXtract methodology combines network-based and information-based frameworks, which is shown to discover causal effects overlooked by classical Granger and Schreiber causality approaches. We showcase the use of CausalXtract to uncover novel causal effects in a tumor-on-chip cellular ecosystem under therapeutically relevant conditions. In particular, we find that cancer-associated fibroblasts directly inhibit cancer cell apoptosis, independently from anticancer treatment. CausalXtract uncovers also multiple antagonistic effects at different time delays. Hence, CausalXtract provides a unique computational tool to interpret live-cell imaging data for a range of fundamental and translational research applications.

Gadolinium oxide nanoparticles as a multimodal contrast enhancement agent for pre-clinical proton imaging

Orthotopic tumor models in pre-clinical translational research are becoming increasingly popular, raising the demands on accurate tumor localization prior to irradiation. This task remains challenging both in x-ray and proton computed tomography (xCT and pCT, respectively), due to the limited contrast of tumor tissue compared to the surrounding tissue. We investigate the feasibility of gadolinium oxide nanoparticles as a multimodal contrast enhancement agent for both imaging modalities. We performed proton radiographies at the experimental room of the Trento Proton Therapy Center using a MiniPIX-Timepix detector and dispersions of gadolinium oxide nanoparticles in sunflower oil with mass fractions up to 8wt%. To determine the minimum nanoparticle concentration required for the detectability of small structures, pCT images of a cylindrical water phantom with cavities of varying gadolinium oxide concentration were simulated using a dedicated FLUKA Monte Carlo framework. These findings are complemented by simulating pCT at dose levels from 80 mGy to 320 mGy of artificially modified murine xCT data, mimicking different levels of gadolinium oxide accumulation inside a fictitious tumor volume. To compare the results obtained for proton imaging to x-ray imaging, cone-beam CT images of a cylindrical PMMA phantom with cavities of dispersions of oil and gadolinium oxide nanoparticles with mass fractions up to 8wt% were acquired at a commercial pre-clinical irradiation setup. For proton radiography, considerable contrast enhancement was found for a mass fraction of 4wt%. Slightly lower values were found for the simulated pCT images at imaging doses below 200 mGy. In contrast, full detectability of small gadolinium oxide loaded structures in xCT at comparable imaging dose is already achieved for 0.5wt%. Achieving such concentrations required for pCT imaging inside a tumor volume inin-vivoexperiments may be challenging, yet it might be feasible using different targeting and/or injection strategies.

Biotechnological Perspectives on the Therapeutic Potential of Phenylpropanoid Cinnamaldehyde in Inflammatory Diseases: Signaling Pathways.

The traditional use of plants of the Cinnamomum genus dates back to traditional Eastern medicine for millennia and they have also been used in Western integrative medicine practices, especially for their anti-inflammatory activity. In the context of chemical diversity, the absolute majority of species in this genus have cinnamaldehyde as the majority component, which in turn holds the title of the active ingredient, whose biological effect profile has already been demonstrated in numerous experiments in acute and chronic inflammatory conditions. In this context, the objective of this research was to investigate how cinnamaldehyde can influence inflammatory phenomena. To this end, the data search was carried out in Pub- Med, SciELO, and LILACS databases using the following descriptors: "cinnamaldehyde OR cinnamaldehyde" and "inflammation". Next, the methodological quality of the selected articles was checked, excluding repeated studies, which were purely in silico and not relevant to the construction of this research. The findings showed cinnamaldehyde to modulate the inflammatory response by inhibiting pro-inflammatory mediators and important signaling trajectories, including NF-κB, NLRP3 inflammasome, TGF-β/Smads, and the NRF2/ARE antioxidant pathway. Cinnamaldehyde's scope of investigation also involves aspects of translational science, exhibiting therapeutic effects in human models, which suggests that it may have clinical relevance. The data support that cinnamaldehyde is a promising candidate for development as a treatment in inflammatory pathologies.