Malignant melanoma (MM) is the most aggressive form of skin cancer, with increasing incidence worldwide. To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for ...MM. Our data highlight the potential of metabolomic characterization of cancer stem cell‐ or serum‐derived exosomes using high‐resolution mass spectrometry for the discovery of clinically useful MM biomarkers.
Malignant melanoma (MM) is the most aggressive and life‐threatening form of skin cancer. It is characterized by an extraordinary metastasis capacity and chemotherapy resistance, mainly due to melanoma cancer stem cells (CSCs). To date, there are no suitable clinical diagnostic, prognostic or predictive biomarkers for this neoplasia. Therefore, there is an urgent need for new MM biomarkers that enable early diagnosis and effective disease monitoring. Exosomes represent a novel source of biomarkers since they can be easily isolated from different body fluids. In this work, a primary patient‐derived MM cell line enriched in CSCs was characterized by assessing the expression of specific markers and their stem‐like properties. Exosomes derived from CSCs and serums from patients with MM were characterized, and their metabolomic profile was analysed by high‐resolution mass spectrometry (HRMS) following an untargeted approach and applying univariate and multivariate statistical analyses. The aim of this study was to search potential biomarkers for the diagnosis of this disease. Our results showed significant metabolomic differences in exosomes derived from MM CSCs compared with those from differentiated tumour cells and also in serum‐derived exosomes from patients with MM compared to those from healthy controls. Interestingly, we identified similarities between structural lipids differentially expressed in CSC‐derived exosomes and those derived from patients with MM such as the glycerophosphocholine PC 16:0/0:0. To our knowledge, this is the first metabolomic‐based study aimed at characterizing exosomes derived from melanoma CSCs and patients' serum in order to identify potential biomarkers for MM diagnosis. We conclude that metabolomic characterization of CSC‐derived exosomes sets an open door to the discovery of clinically useful biomarkers in this neoplasia.
Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases ...significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge.
To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management.
In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM.
We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample.
These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.
OBJECTIVE: Medical nutrition therapy provides the opportunity to compensate for muscle wasting and immune response activation during stress and trauma. The objective of this systematic review is to ...assess the safety and effectiveness of early enteral nutrition (EEN) in adults with sepsis or septic shock. METHODS: The MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and ICTRP tools were searched from inception until July 2023. Conference proceedings, the reference lists of included studies, and expert content were queried to identify additional publications. Two review authors completed the study selection, data extraction, and risk of bias assessment; disagreements were resolved through discussion. Inclusion criteria were randomized controlled trials (RCTs) and non-randomized studies (NRSs) comparing the administration of EEN with no or delayed enteral nutrition (DEE) in adult populations with sepsis or septic shock. RESULTS: Five RCTs (n = 442 participants) and ten NRSs (n = 3724 participants) were included. Low-certainty evidence from RCTs and NRSs suggests that patients receiving EEN could require fewer days of mechanical ventilation (MD −2.65; 95% CI, −4.44–0.86; and MD −2.94; 95% CI, −3.64–−2.23, respectively) and may show lower SOFA scores during follow-up (MD −1.64 points; 95% CI, −2.60–−0.68; and MD −1.08 points; 95% CI, −1.90–−0.26, respectively), albeit with an increased frequency of diarrhea episodes (OR 2.23, 95% CI 1.115–4.34). Even though the patients with EEN show a lower in-hospital mortality rate both in RCTs (OR 0.69; 95% CI, 0.39–1.23) and NRSs (OR 0.89; 95% CI, 0.69–1.13), this difference does not achieve statistical significance. There were no apparent differences for other outcomes. CONCLUSIONS: Low-quality evidence suggests that EEN may be a safe and effective intervention for the management of critically ill patients with sepsis or septic shock.
Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) ...has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma.
The objective of this work was to ascertain the nature of the components responsible for the reducing and stabilizing properties of Zostera noltii extracts that lead to gold nanoparticle formation ...using chemical techniques of analysis. In order to achieve this aim, we try the synthesis of AuNPs with three different extracts from plants collected in the Bay of Cádiz (Spain). The n-butanol extract produced the best results. Taking this into account, four fractions were isolated by Sephadex LH-20 column chromatography from this extract and we studied their activity. The chemical study of these fractions led to the isolation of several flavone sulfates and these were identified as the species' responsible for the formation and stabilization of the AuNPs. Flavone sulfates were purified by high performance liquid chromatography and the structures were established by means of spectroscopic methods nuclear magnetic resonance and mass spectroscopy. AuNPs have an average lifetime of about 16weeks. Additionally, the morphology and crystalline phase of the gold nanoparticles were characterized by transmission electron microscopy. The composition of the nanoparticles was evaluated by electron diffraction and energy dispersive X-ray spectroscopy. An 88% of the gold nanoparticles has a diameter in the range 20–35nm, with an average size of 26±2nm.
Synthesis process of AuNp from Z. noltii fractions extract. Display omitted
•We determine the components of the Z. noltii extracts, that lead to gold nanoparticle formation.•Components were purified by HPLC and structures were established by (NMR, MS).•The AuNPs stability has been studied by UV–vis spectroscopy.•The morphology and crystalline phase of AuNPs have been characterized by TEM.•We propose a biosynthesis of gold nanoparticles using Zostera noltii extract.
This is the first report of the health economic benefits derived from preventing infections through Immunoglobulin Replacement Therapy (IgRT) in patients with secondary immunodeficiency due to ...hematological malignancies. We conducted a retrospective population-based cohort study using patient medical history and pharmacy data from the Hospital Clínico San Carlos for 21 patients between 2011 and 2020. The pharmacoeconomic impact of using prophylactic IgRT was assessed by comparing characteristics of the SID patients 1 year before and after initiating IgRT measured by direct medical and tangible indirect costs. Results indicate a marked reduction in hospitalization days following IgRT initiation, decreasing from an average of 13.9 to 6.1 days per patient, with the elimination of ICU admissions. While emergency department visits decreased significantly, the number of routine consultations remained unchanged. Notably, absenteeism from work dropped substantially. The financial analysis revealed significant reductions in medication use and fewer ancillary tests, resulting in considerable cost savings. Specifically, total expenditure dropped from €405,088.18 pre-IgRT to €295,804.42 post-IgRT—including the cost of IgRT itself at €156,309.60. Overall, the annual savings amounted to €109,283.84, validating the cost-effectiveness of IgRT in managing SID in patients with hematological cancers.
Olive leaf, as an important by-product of olive farming, is generated from the pruning and harvesting of olive trees and represents >10 % of the total olive weight. The present study was conducted to ...evaluate the composition, functional and structural characterizations, as well as the in vitro digestibility of olive leaf proteins isolated from ultrasonic-assisted extraction, comparing to classical and industrial techniques. The ultrasound-assisted extraction of olive leaf protein was optimized by the simultaneous maximization of the yield and purity of protein using a Box-Behnken design (BBD) of response surface methodology (RSM). The results indicated that the optimal extraction conditions were as follows: pH of 10.99, temperature of 40.48 °C, sonication time of 47.25 min, and solvent/solid ratio of 24.08 mL/g. Under these conditions, the extraction yield and protein content were 11.67 and 51.2 %, respectively, which were significantly higher than those obtained by the conventional techniques. Regarding the functionality of protein, extraction technique had significant impacts on the structural and functional properties of proteins. In general, ultrasound assisted extraction had higher solubility, and better foaming and thermal properties and in vitro digestibility but lower emulsifying stability and fluid binding capacity compared to conventional ones. Ultrasound-assisted alkaline extraction has great potential to produce edible olive leaf protein with modified functional properties that can be used for various aims in the food applications.
Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess ...the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.
An ultrasound-assisted method was used for the extraction of phenolics from defatted black cumin seeds (Nigella sativa L.), and the effects of several extraction factors on the total phenolic content ...and DPPH radical scavenging activity were investigated. To improve the extraction efficiency of phenolics from black cumin seed by ultrasonic-assisted extraction, the optimal extraction conditions were determined as follows: ethanol concentration of 59.1%, extraction temperature of 44.6 °C and extraction time of 32.5 min. Under these conditions, the total phenolic content and DPPH radical scavenging activity increased by about 70% and 38%, respectively, compared with conventional extraction. Furthermore, a complementary quantitative analysis of individual phenolic compounds was carried out using the HPLC-UV technique. The phenolic composition revealed high amounts of epicatechin (1.88–2.37 mg/g) and rutin (0.96–1.21 mg/g) in the black cumin seed extracts. Ultrasonic-assisted extraction can be a useful extraction method for the recovery of polyphenols from defatted black cumin seeds.
Plant-based proteins are gaining in attraction compared with animal-based proteins due to their superior ethical profiles, growing concerns on the part of various organizations about animal health ...and welfare, and increased global greenhouse-gas emissions in meat production. In this study, the response surface methodology (RSM) using a Box-Behnken design (BBD) was applied to optimize the ultrasound-assisted alkaline extraction of cherimoya-seed proteins as valuable by-products. The effects of three pH, temperature, and time factors on the protein-extraction yield and protein content were investigated. The pH at 10.5 and temperature of 41.8 °C for 26.1 min were considered the optimal ultrasound-assisted alkaline-extraction conditions since they provided the maximum extraction yield (17.3%) and protein content (65.6%). An established extraction technique was employed to enhance the cherimoya-seed protein yield, purity, and functional properties. A thermogravimetric analysis (TGA) of the samples showed that the ultrasound-assisted alkaline extraction improved the thermal stability of the protein concentrate.
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