Nanosystems with potential application as carriers for skin depigmenting actives.

Hyperpigmentation is a skin disorder characterized by excessive production of melanin in the skin and includes dyschromias such as post-inflammatory hyperchromias, lentigens, melasma and chloasma. Topical products containing depigmenting agents offer a less aggressive treatment option for hyperpigmentation compared to methods like chemical peels and laser sessions. However, some of these agents can cause side effects such as redness and skin irritation. Encapsulating these actives in nanosystems shows promise in mitigating these effects and improving product safety and efficacy. In addition, nanocarriers have the ability to penetrate the skin, potentially allowing for targeted delivery of actives to the affected areas. The most commonly investigated nanosystems are nanoemulsions, vesicular nanosystems and nanoparticles, in which different materials can be used to generate different compositions in order to improve the properties of these nanocarriers. Nanocarriers have already been widely explored, but it is necessary to understand the evolution of these technologies when applied to the treatment of skin hyperchromias. Therefore, this literature review aims to present the state of the art over the last 15 years on the use of nanosystems as a potential strategy for encapsulating depigmenting actives for potential application in cosmetic products for skin hyperchromia. By providing a comprehensive overview of the latest research findings and technological advances, this article can contribute to improving the care and quality of life of people affected by this skin condition.

Interaction between plasma phospholipid odd-chain fatty acids and GAD65 autoantibodies on the incidence of adult-onset diabetes: the EPIC-InterAct case-cohort study.

AIMS/HYPOTHESIS: Islet autoimmunity may progress to adult-onset diabetes. We investigated whether circulating odd-chain fatty acids (OCFA) 15:0 and 17:0, which are inversely associated with type 2 diabetes, interact with autoantibodies against GAD65 (GAD65Ab) on the incidence of adult-onset diabetes. METHODS: We used the European EPIC-InterAct case-cohort study including 11,124 incident adult-onset diabetes cases and a subcohort of 14,866 randomly selected individuals. Adjusted Prentice-weighted Cox regression estimated HRs and 95% CIs of diabetes in relation to 1 SD lower plasma phospholipid 15:0 and/or 17:0 concentrations or their main contributor, dairy intake, among GAD65Ab-negative and -positive individuals. Interactions between tertiles of OCFA and GAD65Ab status were estimated by proportion attributable to interaction (AP). RESULTS: Low concentrations of OCFA, particularly 17:0, were associated with a higher incidence of adult-onset diabetes in both GAD65Ab-negative (HR 1.55 [95% CI 1.48, 1.64]) and GAD65Ab-positive (HR 1.69 [95% CI 1.34, 2.13]) individuals. The combination of low 17:0 and high GAD65Ab positivity vs high 17:0 and GAD65Ab negativity conferred an HR of 7.51 (95% CI 4.83, 11.69), with evidence of additive interaction (AP 0.25 [95% CI 0.05, 0.45]). Low dairy intake was not associated with diabetes incidence in either GAD65Ab-negative (HR 0.98 [95% CI 0.94, 1.02]) or GAD65Ab-positive individuals (HR 0.97 [95% CI 0.79, 1.18]). CONCLUSIONS/INTERPRETATION: Low plasma phospholipid 17:0 concentrations may promote the progression from GAD65Ab positivity to adult-onset diabetes.

Repeat-based phylogenomics shed light on unclear relationships in the monocentric genus Juncus L. (Juncaceae).

The repetitive fraction (repeatome) of eukaryotic genomes is diverse and usually fast evolving, being an important tool for clarify plant systematics. The genus Juncus L. comprises 332 species, karyotypically recognized by having holocentric chromosomes. However, four species were recently described as monocentric, yet our understanding of their genome evolution is largely masked by unclear phylogenetic relationships. Here, we reassess the current Juncus systematics using low-coverage genome skimming data of 33 taxa to construct repeats, nuclear rDNA and plastome-based phylogenetic hypothesis. Furthermore, we characterize the repeatome and chromosomal distribution of Juncus-specific centromeric repeats/CENH3 protein to test the monocentricity reach in the genus. Repeat-base phylogenies revealed topologies congruent with the rDNA tree, but not with the plastome tree. The incongruence between nuclear and plastome chloroplast dataset suggest an ancient hybridization in the divergence of Juncotypus and Tenageia sections 40 Myr ago. The phylogenetic resolution at section level was better fitted with the rDNA/repeat-based approaches, with the recognition of two monophyletic sections (Stygiopsis and Tenageia). We found specific repeatome trends for the main lineages, such as the higher abundances of TEs in the Caespitosi and Iridifolii + Ozophyllum clades. CENH3 immunostaining confirmed the monocentricity of Juncus, which can be a generic synapomorphy for the genus. The heterogeneity of the repeatomes, with high phylogenetic informativeness, identified here may be correlated with their ancient origin (56 Mya) and reveals the potential of comparative genomic analyses for understanding plant systematics and evolution.

Diffusion MRI signal cumulants and hepatocyte microstructure at fixed diffusion time: Insights from simulations, 9.4T imaging, and histology.

PURPOSE: Relationships between diffusion-weighted MRI signals and hepatocyte microstructure were investigated to inform liver diffusion MRI modeling, focusing on the following question: Can cell size and diffusivity be estimated at fixed diffusion time, realistic SNR, and negligible contribution from extracellular/extravascular water and exchange? METHODS: Monte Carlo simulations were performed within synthetic hepatocytes for varying cell size/diffusivity L / D0 , and clinical protocols (single diffusion encoding; maximum b-value: {1000, 1500, 2000} s/mm2 ; 5 unique gradient duration/separation pairs; SNR = { ∞ , 100, 80, 40, 20}), accounting for heterogeneity in (D0,L) and perfusion contamination. Diffusion ( D ) and kurtosis ( K ) coefficients were calculated, and relationships between (D0,L) and (D,K) were visualized. Functions mapping (D,K) to (D0,L) were computed to predict unseen (D0,L) values, tested for their ability to classify discrete cell-size contrasts, and deployed on 9.4T ex vivo MRI-histology data of fixed mouse livers RESULTS: Relationships between (D,K) and (D0,L) are complex and depend on the diffusion encoding. Functions mapping D,K to (D0,L) captures salient characteristics of D0(D,K) and L(D,K) dependencies. Mappings are not always accurate, but they enable just under 70% accuracy in a three-class cell-size classification task (for SNR = 20, bmax = 1500 s/mm2 , δ = 20 ms, and Δ = 75 ms). MRI detects cell-size contrasts in the mouse livers that are confirmed by histology, but overestimates the largest cell sizes. CONCLUSION: Salient information about liver cell size and diffusivity may be retrieved from minimal diffusion encodings at fixed diffusion time, in experimental conditions and pathological scenarios for which extracellular, extravascular water and exchange are negligible.

One door closes, another opens: when nodulation impairment with natural hosts extends rhizobial host-range.

The rhizobium-legume symbiosis is the best-understood plant-microbe association. The high degree of specificity observed in this relationship is supported by a complex exchange of signals between the two components of the symbiosis. Findings reported in last years indicate that multiple molecular mechanisms, such as the production of a particular set of nodulation factors at a very specific concentration or a suitable arsenal of effectors secreted through the type III secretion system, have been adjusted during evolution to ensure and optimize the recognition of specific rhizobial strains by its legume host. Qualitative or quantitative changes in the production of these symbiotic molecular determinants are detrimental for nodulation with its natural host but, in some cases, can also result beneficial for the rhizobium since it extends the nodulation host-range to other legumes. Potential repercussion of the extension in the nodulation host-range of rhizobia is discussed.

Hyperprogressive Disease: Main Features and Key Controversies.

Along with the positioning of immunotherapy as a preferential treatment for a wide variety of neoplasms, a new pattern of response consisting in a sudden acceleration of tumor growth has been described. This phenomenon has received the name of "hyperprogressive disease", and several definitions have been proposed for its identification, most of them relying on radiological criteria. However, due to the fact that the cellular and molecular mechanisms have not been elucidated yet, there is still some debate regarding whether this fast progression is induced by immunotherapy or only reflects the natural course of some highly aggressive neoplasms. Moreover, contradictory results of trials including patients with different cancer types suggest that both the incidence, the associated factors and the implications regarding prognosis might differ depending on tumor histology. This article intends to review the main publications regarding this matter and critically approach the most controversial aspects.

Genetic analysis for carrier diagnosis in hemophilia A and B in the Mexican population: 25 years of experience.

Our 25 years of experience in carrier diagnosis of hemophilia A (HA) and B (HB) in Mexican population comprises linkage analysis of intragenic F8/F9 neutral variants along with, in severe HA (SHA), detection of F8 int22h and int1h inversions. In symptomatic carriers (SCs) we explored Lyonization to explain their symtomatology. From a DNA-Bank of 3,000 samples, intragenic restriction fragment length (RFLPs) and short tandem repeats (STRs) of F8/F9 genes were assessed by PCR-PAGE and GeneScan. In SHA patients, F8 inversions were detected by inverse shifting-PCR/diagnostic and complementary tests. In SCs, we evaluated hemorrhagic symptoms, clotting FVIII/FIX and X-chromosome inactivation (XCI) patterns were assessed by HUMARA assay and the search of XIST promoter pathogenic variants. Informativeness of linkage analysis for HA carrier diagnosis with RFLP's/STR's increased to 74% and reached 80% with five RFLPs for HB. Combined Inv22/Inv1 diagnosed 113 possible carriers, three de novo Inv22-1, and confirmed 45 mothers as obligate or sporadic carriers. Among 21 SCs, four showed extreme skewed XCI pattern (~80:20) but had normal karyotype and no C43G pathogenic variant in XIST promoter. Clotting FVIII/FIX correlated with the active X in leukocytes. Our data integrate the largest comprehensive research worldwide on the molecular diagnosis of HA and HB carriers in terms of the number of studied and diagnosed cases, in addition to the genetic analysis in SCs. Intragenic RFLPs and STRs of F8/F9 genes along with F8 int22h/int1h inversions in SHA emerge as optimal variants for molecular diagnosis in Mexican population. In counseling SCs, inheritance of skewed X-inactivation should be considered.

Stabilized collagen matrix dressing improves wound macrophage function and epithelialization.

Decellularized matrices of biologic tissue have performed well as wound care dressings. Extracellular matrix-based dressings are subject to rapid degradation by excessive protease activity at the wound environment. Stabilized, acellular, equine pericardial collagen matrix (sPCM) wound care dressing is flexible cross-linked proteolytic enzyme degradation resistant. sPCM was structurally characterized utilizing scanning electron and atomic force microscopy. In murine excisional wounds, sPCM was effective in mounting an acute inflammatory response. Postwound inflammation resolved rapidly, as indicated by elevated levels of IL-10, arginase-1, and VEGF, and lowering of IL-1ß and TNF-α. sPCM induced antimicrobial proteins S100A9 and ß-defensin-1 in keratinocytes. Adherence of Pseudomonas aeruginosa and Staphylococcus aureus on sPCM pre-exposed to host immune cells in vivo was inhibited. Excisional wounds dressed with sPCM showed complete closure at d 14, while control wounds remained open. sPCM accelerated wound re-epithelialization. sPCM not only accelerated wound closure but also improved the quality of healing by increased collagen deposition and maturation. Thus, sPCM is capable of presenting scaffold functionality during the course of wound healing. In addition to inducing endogenous antimicrobial defense systems, the dressing itself has properties that minimize biofilm formation. It mounts robust inflammation, a process that rapidly resolves, making way for wound healing to advance.-El Masry, M. S., Chaffee, S., Das Ghatak, P., Mathew-Steiner, S. S., Das, A., Higuita-Castro, N., Roy, S., Anani, R. A., Sen, C. K. Stabilized collagen matrix dressing improves wound macrophage function and epithelialization.

Psychometric validation of PROMIS® Anxiety and Depression Item Banks for the Brazilian population.

PURPOSE: Scientific evidence indicates that depression and anxiety symptoms may be understood as risk factors associated with the incidence and progression of chronic diseases. Considering the lack of mental health assessment tools that meet strict methodological standards, the authors have chosen to validate the psychometric properties of Anxiety and Depression Item Banks - Emotional Distress domain of the Patient-Reported Outcomes Measurement Information System (PROMIS®) for the Brazilian population. METHODS: In this study, 606 adults responded to the self-administered Anxiety and Depression Item Banks, which were calibrated using Factor Analyses (Exploratory and Confirmatory analysis) and adjustment of the Graded Response Model. Transcultural validity was assessed by Differential Item Functioning (DIF). RESULTS: The two-factor analysis confirmed the unidimensionality of Emotional Distress Items (CFI = 0.96, TLI = 0.96, RMSEA = 0.05). The residual correlation matrix did not identify item pairs with local dependence. Indicators marked with DIF presented a low impact for gender, age, and language variables. The instrument demonstrated greater reliability in the moderate-severe range, indicating that the error reduction is reflected in the - 1.0 to + 3.0 amplitude. CONCLUSION: The psychometric measurements of Anxiety and Depression Item Banks in the Brazilian version were equivalent to those in the original version. Additional research contemplating patients with different levels of emotional distress are necessary to better comprehend the results obtained in this study.

Neurogenic tissue nanotransfection in the management of cutaneous diabetic polyneuropathy.

This work rests on our recent report on the successful use of tissue nanotransfection (TNT) delivery of Ascl1, Brn2, and Myt1l (TNTABM) to directly convert skin fibroblasts into electrophysiologically active induced neuronal cells (iN) in vivo. Here we report that in addition to successful neurogenic conversion of cells, TNTABM caused neurotrophic enrichment of the skin stroma. Thus, we asked whether such neurotrophic milieu of the skin can be leveraged to rescue pre-existing nerve fibers under chronic diabetic conditions. Topical cutaneous TNTABM caused elevation of endogenous NGF and other co-regulated neurotrophic factors such as Nt3. TNTABM spared loss of cutaneous PGP9.5+ mature nerve fibers in db/db diabetic mice. This is the first study demonstrating that under conditions of in vivo reprogramming, changes in the tissue microenvironment can be leveraged for therapeutic purposes such as the rescue of pre-existing nerve fibers from its predictable path of loss under conditions of diabetes.

Hypercaloric Diet-Induced Obesity and Obesity-Related Metabolic Disorders in Experimental Models.

Overnutrition and obesity have developed into a major public health problem across different parts of the world. Epidemiological studies have shown that excessive intake of dietary components, such as fatty acids and/or sugars, can promote obesity. In this context, the use of dietary intervention in animal models that respond to a diet similar to humans is useful to understand this preventable, multifactorial disease. The aim of this chapter is to aid researchers in choosing specific nutritional interventions and animal strains to induce obesity and obesity-related morbidities in experimental models.

F8 inversions of introns 22 and 1 confer a moderate risk of inhibitors in Mexican patients with severe hemophilia A. Concordance analysis and literature review.

Intron-22 (Inv22) and intron-1 (Inv1) inversions account for approximately one half of all severe cases of hemophilia A (SHA) worldwide. Inhibitor development against exogenous factor VIII (FVIII) represents a major complication in HA. The causative F8 mutation is considered the most decisive factor conditioning inhibitor development. We aimed to investigate prevalence of Inv22 and Inv1 mutations, and its association as risk factors for developing inhibitors to FVIII. We investigated Inv22 and Inv1 in 255 SHA Mexican patients from 193 unrelated families using the inverse shifting-polymerase chain reaction (IS-PCR). We analyzed the association between inversions and inhibitor development via logistic regression introducing as covariates the populations, the inversions, F8-haplotypes and the age of patients at enrollment. Inv22 was found in 91/193 (47.2%: 38.9% exhibited Inv22-1 and 8.3% Inv22-2), and Inv1 in 2/193 (1.0%) independent families. Absolute inhibitor prevalence (IP) for Inv22 in unrelated patients was 15% (10-19). The cohorts and age of patients were independent predictors of inhibitor risk, but not inversions or haplotypes. Inversions presence in our population was associated to a moderate risk of developing inhibitors. Inv1 was found for the first time in two Mexican families. A relevant genetic component was observed by the strong concordance among brother-pairs.

Prognostic clinical indicators of short-term survival for ineffective breathing pattern in children with acute respiratory infection.

AIMS AND OBJECTIVES: To identify prognostic clinical indicators of short-term survival for ineffective breathing pattern in children with acute respiratory infection. BACKGROUND: Despite the studies of survival for nursing diagnosis, there is not enough evidence about the clinical indicators that are associated with a worse prognosis for ineffective breathing pattern. DESIGN: A prospective cohort study. METHODS: One hundred and thirty-six children were followed up for a minimum of six and a maximum of 10 consecutive days. The survival rate for ineffective breathing pattern was calculated using Nelson-Aalen's method. An extended Cox model was adjusted to identify the main prognostic clinical indicators for this nursing diagnosis. RESULTS: Over half of the sample had an ineffective breathing pattern at the first evaluation. The occurrence of new cases was observed until the ninth day of monitoring, and the survival rate after this day was low. According to the Cox model, the main clinical indicators of a poor prognosis were an abnormal breathing pattern, the use of accessory muscles, dyspnoea and increase in the anterior-posterior chest diameter. CONCLUSIONS: Children with acute respiratory infection who present with an abnormal breathing pattern, the use of accessory muscles to breathe, dyspnoea and increased anterior-posterior diameter have a poor prognosis for an ineffective breathing pattern. RELEVANCE TO CLINICAL PRACTICE: Survival analyses of nursing diagnoses allow the identification of clinical indicators that can be used in clinical practice as prognostic markers. The identification of indicators associated with a poor clinical prognosis allows nurses to intervene early and to maximise the possibility of a good outcome.

Isolation, Quantification, and Visualization of Extracellular Membrane Vesicles in Rhizobia Under Free-Living Conditions.

Rhizobia are a group of soil proteobacteria that are able to establish a symbiotic interaction with legumes. These bacteria are capable to fix atmospheric nitrogen into ammonia within specific plant root organs called nodules. The rhizobia-legume interaction is established by a complex molecular dialogue that starts with flavonoids exudated by the plant roots. In response, signaling molecules known as Nod factors (NFs) are secreted by the bacteria. These factors are sensed by specific plant receptors that trigger a downstream signaling cascade leading to rhizobium-specific intracellular colonization of the root hair via the formation of infection threads and the eventual development of nodules on roots. In these organs, rhizobia can fix nitrogen from the atmosphere for the plant in exchange for photosynthates and the appropriate environment for nitrogen fixation. Recently, it has been demonstrated that extracellular membrane vesicles (EMVs) produced by some rhizobia carry NFs. EMVs are proteolipidic structures that are secreted to the milieu from the bacterial membranes and are involved in several important biological processes, including intercellular communication. Thus far, little is known about rhizobia vesicles, and further studies are needed to understand their functions, including their role as transporting vessels of signaling molecules during the process of symbiosis. Here, we present a detailed protocol to isolate high-purity EMVs from free-living cultured rhizobia, test their integrity, and quantify their abundance.

Paracoccidioidomycosis manifested by sarcoid-like cutaneous lesions with severe systemic disease: a rare and challenging diagnosis.

Cutaneous involvement in paracoccidioidomycosis (PCM) can exhibit a highly polymorphic spectrum. The infiltrative pattern corresponds to up to 26.6% of observed skin lesions, including sarcoid-like plaques, a rare presentation of cutaneous lesions in PCM. This clinical expression is almost exclusively cutaneous, and its histology reveals a tuberculoid granuloma with a scarcity of fungi, leading to misdiagnosis as other granulomatous diseases. Here, we report a rare form of chronic multifocal paracoccidioidomycosis manifesting as sarcoid-like skin lesions misdiagnosed as granulomatous rosacea in a patient with severe systemic disease.

Determination of resistance at zero and infinite frequencies in bioimpedance spectroscopy for assessment of body composition in babies.

Objective. Bioimpedance spectroscopy (BIS) is a popular technique for the assessment of body composition in children and adults but has not found extensive use in babies and infants. This due primarily to technical difficulties of measurement in these groups. Although improvements in data modelling have, in part, mitigated this issue, the problem continues to yield unacceptably high rates of poor quality data. This study investigated an alternative data modelling procedure obviating issues associated with BIS measurements in babies and infants.Approach.BIS data are conventionally analysed according to the Cole model describing the impedance response of body tissues to an appliedACcurrent. This approach is susceptible to errors due to capacitive leakage errors of measurement at high frequency. The alternative is to model BIS data based on the resistance-frequency spectrum rather than the reactance-resistance Cole model thereby avoiding capacitive error impacts upon reactance measurements.Main results.The resistance-frequency approach allowed analysis of 100% of data files obtained from BIS measurements in 72 babies compared to 87% successful analyses with the Cole model. Resistance-frequency modelling error (percentage standard error of the estimate) was half that of the Cole method. Estimated resistances at zero and infinite frequency were used to predict body composition. Resistance-based prediction of fat-free mass (FFM) exhibited a 30% improvement in the two-standard deviation limits of agreement with reference FFM measured by air displacement plethysmography when compared to Cole model-based predictions.Significance.This study has demonstrated improvement in the analysis of BIS data based on the resistance frequency response rather than conventional Cole modelling. This approach is recommended for use where BIS data are compromised by high frequency capacitive leakage errors such as those obtained in babies and infants.

Factors associated with domestic violence in pregnant women during the COVID-19 pandemic: Araraquara Cohort study.

AIMS AND METHOD: This cross-sectional study, carried out from 2021 to 2022, investigated the factors associated with domestic violence in 400 Brazilian pregnant women during the COVID-19 pandemic. Violence was assessed with the World Health Organization's Violence Against Women questionnaire and the Abuse Assessment Screen. Demographic, socioeconomic, obstetric, lifestyle and mental health data were collected. RESULTS: Violence at any time in their lives was reported by 52.2% of the women, and psychological violence was the most prevalent type (19.5%). Violence was associated with being single and mental health changes. Pregnant women exposed to any lifetime violence and psychological violence were, respectively, 4.67 and 5.93 times more likely to show mental health changes compared with women with no reported violence. CLINICAL IMPLICATIONS: Training health professionals involved in prenatal care in the early detection of single women and women with mental health changes could be important in preventing domestic violence.

A Micro-scale Humanized Ventilator-on-a-Chip to Examine the Injurious Effects of Mechanical Ventilation.

Patients with compromised respiratory function frequently require mechanical ventilation to survive. Unfortunately, non-uniform ventilation of injured lungs generates complex mechanical forces that lead to ventilator induced lung injury (VILI). Although investigators have developed lung-on-a-chip systems to simulate normal respiration, modeling the complex mechanics of VILI as well as the subsequent recovery phase is a challenge. Here we present a novel humanized in vitro ventilator-on-a-chip (VOC) model of the lung microenvironment that simulates the different types of injurious forces generated in the lung during mechanical ventilation. We used transepithelial/endothelial electrical resistance (TEER) measurements to investigate how individual and simultaneous application of the different mechanical forces alters real-time changes in barrier integrity during and after injury. We find that compressive stress (i.e. barotrauma) does not significantly alter barrier integrity while over-distention (20% cyclic radial strain, volutrauma) results in decreased barrier integrity that quickly recovers upon removal of mechanical stress. Conversely, surface tension forces generated during airway reopening (atelectrauma), result in a rapid loss of barrier integrity with a delayed recovery relative to volutrauma. Simultaneous application of cyclic stretching (volutrauma) and airway reopening (atelectrauma), indicate that the surface tension forces associated with reopening fluid-occluded lung regions is the primary driver of barrier disruption. Thus, our novel VOC system can monitor the effects of different types of injurious forces on barrier disruption and recovery in real-time and can be used to identify the biomechanical mechanisms of VILI.

Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma represents one of the solid tumors showing the worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response. In this study, surgical tumor tissue and sequential blood samples were analyzed by next-generation sequencing and were correlated with clinical and pathological characteristics. Thirty resectable/borderline pancreatic ductal adenocarcinoma patients treated at the Hospital Universitario de Navarra were included. Circulating tumoral DNA sequencing identified pathogenic variants in KRAS and TP53, and in other cancer-associated genes. Pathogenic variants at diagnosis were detected in patients with a poorer outcome, and were correlated with response to neoadjuvant therapy in borderline pancreatic ductal adneocarcinoma patients. Higher variant allele frequency at diagnosis was associated with worse prognosis, and thesum of variant allele frequency was greater in samples at progression. Our results build on the potential value of circulating tumor DNA for non-metastatic pancreatic ductal adenocarcinoma patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings.

Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution.

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.