Antiangiogenic Potential of an Olive Oil Extract: Insights from a Proteomic Study.

Extra virgin olive oil (EVOO), a staple of the Mediterranean diet, is rich in phenolic compounds recognized for their potent bioactive effects, including anticancer and anti-inflammatory properties. However, its effects on vascular health remain relatively unexplored. In this study, we examined the impact of a "picual" EVOO extract from Jaén, Spain, on endothelial cells. Proteomic analysis revealed the modulation of angiogenesis-related processes. In subsequent in vitro experiments, the EVOO extract inhibited endothelial cell migration, adhesion, invasion, ECM degradation, and tube formation while inducing apoptosis. These results provide robust evidence of the extract's antiangiogenic potential. Our findings highlight the potential of EVOO extracts in mitigating angiogenesis-related pathologies, such as cancer, macular degeneration, and diabetic retinopathy.

Exploring active ageing in a community-based living environment: an ethnographic study in the Western Norway context.

Background: Age-friendly environments intend to promote active ageing by facilitating social, mental, and physical participation. This could potentially delay the onset of chronic complex conditions, enabling people to live longer independently at home, and prevent loneliness. This study investigates a community-based living environment in Norway called Helgetun and aims to explore how it can facilitate active ageing. Method: We chose an ethnographic approach consisting of observation, informal conversations, and in-depth semi-structured interviews with 15 residents (11 female, 4 male, ages 62-84). We analysed the data using reflexive thematic analysis. Result: We developed three themes on facilitating active ageing in this living environment: maintaining self-identity, experiencing growth and development, and feeling a sense of belonging. These themes were related to physical activity levels, social engagement, and overall satisfaction with the living environment. Maintaining self-identity concerned getting a new role in life as well as access to meaningful activities. Experiencing growth and development involved being exposed to new activities, learning new skills, and experiencing mastery. Lastly, feeling a sense of belonging meant feeling safe and part of a group, as well as receiving social support and help. This feeling of social connectedness and safety was reflected in their experience with the COVID-19 pandemic, in which most felt relatively unaffected, suggesting that this way of living could increase reliance among this age group. Conclusion: Having a flexible structure, adapting to the core needs and individual resources of the residents, can facilitate active ageing in community-based living environments. Our findings contribute to the growing evidence that these environments increase social and physical engagement, whilst reducing social isolation and loneliness. These findings may be particularly relevant in a Norwegian context-where older adults are less dependent on family for care-and are meant as grounding points for policymakers to reflect upon designing future senior living.

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

Dietary oleacein, a secoiridoid from extra virgin olive oil, prevents collagen-induced arthritis in mice.

Olacein (OLA), one of the main secoiridoids derived from extra virgin olive oil (EVOO), has been shown to modulate oxidative and inflammatory responses in various pathological conditions; however, its potential benefit in joint disorders such as rheumatoid arthritis (RA) is unknown. Therefore, this study was designed to evaluate the preventive role of the effects of an OLA-supplemented diet in the murine model of collagen-induced arthritis (CIA), delving into the possible mechanisms and signaling pathways involved. Animals were fed an OLA-enriched preventive diet for 6 weeks prior to CIA induction and until the end of the experimental time course. On day 43 after the first immunization, mice were sacrificed: blood was collected, and paws were histologically and biochemically processed. Dietary OLA prevented collagen-induced rheumatic bone, joint and cartilage conditions. Circulating matrix metalloproteinase (MMP)-3 and proinflammatory cytokine (IL-6, IL-1ß, TNF-α, IL-17) levels were significantly decreased in the joint, as well as MMP-9 and cathepsin-K (CatK) expression in secoiridoid-fed animals. In addition, dietary OLA was able to decrease COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms possibly involved in these protective effects could be related to the activation of the Nrf-2/HO-1 axis and the inhibition of proinflammatory signaling pathways, including JAK-STAT, MAPKs and NF-κB, involved in the production of inflammatory and oxidative mediators. These results support the interest of OLA, as a nutraceutical intervention, in the management of RA.

Ultrasound for assessing tumor spread in ovarian cancer. A systematic review of the literature and meta-analysis.

In this review, we aimed to assess the diagnostic performance of ultrasound for assessing the tumor spread in the abdomen in women with ovarian cancer. A search for studies evaluating the role of ultrasound for assessing intrabdominal tumor spread in women with ovarian cancer compared to surgery from January 2011 to March 2023 was performed in PubMed/MEDLINE, Web of Science, and Scopus databases. The Quality Assessment of Diagnostic Accuracy Studies 2 evaluated the quality of the studies (QUADAS-2). All analyses were performed using MIDAS and METANDI commands in STATA 12.0 software. We identified 1552 citations. After exclusions, five studies comprising 822 women were included. Quality of studies were considered as good, except for patient selection as all studies were considered as having high risk of bias. The pooled sensitivity and specificity could be calculated for three anatomical areas (recto-sigma, major omentum and root of mesentery) and the presence of ascites. The pooled sensitivity and specificity for detecting disease in the recto-sigma, major omentum and root of mesentery were 0.83 and 0.95, 0.87 and 0.87, and 0.29 and 0.99, respectively. The pooled sensitivity and specificity for detecting ascites was 0.95 and 0.91, respectively. There is evidence that ultrasound offers good diagnostic performance for evaluating the intra-abdominal extent of disease in women with suspected ovarian cancer.

Proteomic and Low-Polar Metabolite Profiling Reveal Unique Dynamics in Fatty Acid Metabolism during Flower and Berry Development of Table Grapes.

Grapevine development and ripening are complex processes that involve several biochemical pathways, including fatty acid and lipid metabolism. Fatty acids are essential components of lipids, which play crucial roles in fruit maturation and flavor development. However, the dynamics of fatty acid metabolism in grape flowers and berries are poorly understood. In this study, we present those dynamics and investigate the mechanisms of fatty acid homeostasis on 'Thompson Seedless' berries using metabolomic and proteomic analyses. Low-polar metabolite profiling indicated a higher abundance of fatty acids at the pre-flowering and pre-veraison stages. Proteomic analyses revealed that grape flowers and berries display unique profiles of proteins involved in fatty acid biosynthesis, triacylglycerol assembly, fatty acid ß-oxidation, and lipid signaling. These findings show, for the first time, that fatty acid metabolism also plays an important role in the development of non-oil-rich tissues, opening new perspectives about lipid function and its relation to berry quality.

Epidemiology of Work-Related Traumatic Brain Injury and COVID-19 Pandemic Lockdown Consequences: Experience in a Reference Center in Chile.

INTRODUCTION: Work-related traumatic brain injury is a frequent cause of chronic morbidity, mortality, and high treatment costs. Its causes are highly environmentally determined and were affected by COVID-19 pandemic lockdowns. OBJECTIVE: We aimed to describe traumatic brain injury (TBI) epidemiology in working population and evaluate its modifications during the COVID-19 pandemic. METHODS: We performed a 2-year retrospective epidemiological analysis of TBI patients hospitalized in a tertiary work-related hospital before and during the COVID-19 pandemic. RESULTS: In the prepandemic period, TBI patients were predominantly men, with a bimodal age distribution. Crash accidents were the leading work-related traumatic brain injury cause. During COVID-19 pandemic lockdowns, there was a positive correlation between street traffic and TBI rate, presenting increased motor crash accidents as a cause of TBI. CONCLUSIONS: These results are relevant for planning and focalization of resources for TBI prevention.

Sotos Syndrome and Nephrocalcinosis, a Rare But Possible Association due to Impact on Contiguous Genes.

One-month old breastfeeding infant, full-term birth, with normal anthropometric measurements at birth is referred to Pediatric Nephrology due to a nephrocalcinosis. The patient presents dysmorphic features and heart disease. A metabolic study is conducted on blood and urine yielding results within normal parameters, except for renal concentration test and acidification test. At 6 months of age, patient presents overgrowth, which along with other clinical signs arouse suspicion of Sotos Syndrome. Molecular genetic testing detects heterozygous deletion in 5q35 between bands q35.2 and q35.3, affecting genes NSD1, SLC34A1 and FGFR4, which is compatible with this syndrome and with nephrocalcinosis as a rare association.

Pentalogía de Cantrell diagnosticada en el primer trimestre: reporte de caso / Cantrell's pentalogy diagnosed in the first trimester: case report

La pentalogía de Cantrell es una rara anomalía congénita caracterizada por la asociación de ectopia cordis con defectos en la pared toracoabdominal, el diafragma, el esternón y pericárdicos, y anomalías cardíacas intrínsecas. En diagnóstico prenatal, la ecografía se utiliza sistemáticamente entre las 11 y 14 semanas de gestación, evaluando marcadores de alteraciones cromosómicas como la sonolucencia nucal, el hueso nasal y la morfología patológica del ductus venoso, entre otros. Además, permite examinar la anatomía fetal y diagnosticar anomalías mayores, como acrania-anencefalia, holoprosencefalia, defectos de la pared abdominal y toracoabdominal, entre los que se incluye la pentalogía de Cantrell. Se reporta un feto con los hallazgos clásicos de pentalogía de Cantrell, que fue expulsado a las 13 semanas de gestación bajo protocolo de interrupción voluntaria del embarazo. Madre de 23 años, G1P0, sin exposiciones teratogénicas, en cuyo feto se encontró ectopia cordis, asas intestinales e hígado por fuera de la cavidad abdominal en las 10 y 12 semanas de gestación. El objetivo de este estudio es aportar a la literatura un reporte de pentalogía de Cantrell, siendo el primero reportado en Colombia en el primer trimestre de gestación, mostrando la importancia de la ecografía sistemática durante este periodo, en el marco de la posibilidad de interrupción voluntaria del embarazo.

Cantrells pentalogy is a rare congenital anomaly characterized by the association of ectopia cordis with intrinsic cardiac anomalies and various anatomical defects found in the thoracoabdominal wall, diaphragm, sternum and pericardium. Ultrasound is used routinely between 11 and 14 weeks of gestation during prenatal diagnosis. It evaluates markers of chromosomal alterations such as nuchal sonolucency, the nasal bone, and the pathological morphology of the ductus venosus, among others. Furthermore, it allows the diagnosis of altered fetal anatomy and major abnormalities such as acrania-anencephaly, holoprosencephaly, abdominal and thoraco-abdominal wall defects including Cantrells pentalogy. In this case report, we present a fetus with the classic findings of Cantrells pentalogy, which was expelled during the 13th week of gestation under the protocol of voluntary interruption of pregnancy. The mother, a 23-year-old woman, G1P0, without teratogenic exposures, in whom during the routine ultrasound of the 10th and 12th weeks of gestation ectopia cordis, intestinal loops and liver outside the abdominal cavity were found on the fetus. The main objective of this study is to contribute to the literature a case report of pentalogy of Cantrell, diagnosed through prenatal ultrasound, being the first reported in Colombia during first trimester of gestation, showing the importance of routine ultrasound, in the context of access to a voluntary termination of pregnancy.

Anti-angiogenic effects of oleacein and oleocanthal: New bioactivities of compounds from Extra Virgin Olive Oil.

Phenolic compounds play a key role in the health benefits of Extra Virgin Olive Oil (EVOO). Among these molecules, the focus has been recently put on (-)-oleocanthal and (-)-oleacein, for which anti-cancer and angiogenesis-related findings have been reported. Here, we explored the modulatory action of (-)-oleocanthal and (-)-oleacein on angiogenesis, the process by which new vessels are created from pre-existent ones, which is directly linked to tumor progression and other pathological conditions. Two in vivo models strongly sustained by angiogenesis, and an in vitro model of endothelial cells to study different steps of angiogenesis, were used. In vivo evidence pointed to the anti-angiogenic effects of both compounds in vivo. In vitro, (-)-oleacein and (-)-oleocanthal inhibited the proliferation, invasion, and tube formation of endothelial cells, and (-)-oleacein significantly repressed migration and induced apoptosis in these cells. Mechanistically, the compounds modulated signaling pathways related to survival and proliferation, all at concentrations of physiological relevance for humans. We propose (-)-oleacein and (-)-oleocanthal as good candidates for angioprevention and for further studies as modulators of angiogenesis in clinical interventions, and as interesting functional claims for the food industry. Chemical compounds studied in this article: Oleocanthal (PubChem CID: 11652416); Oleacein (PubChem CID: 18684078).

Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with low-grade endometrioid endometrial cancer: A systematic review and head-to-head meta-analysis.

PURPOSE: We aimed to compare the diagnostic performance of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVS) for detecting myometrial invasion (MI) in patients with low-grade endometrioid endometrial carcinoma. METHODS: A comprehensive search of MEDLINE (Pubmed), Web of Science, Embase and Scopus (from January 1990 to December 2022) was performed for articles comparing TVS and MRI in the evaluation of myometrial infiltration in low-grade (grade 1 or 2) endometrioid endometrial carcinoma in the same group of patients. We used QUADAS-2 tool for assessing the risk of bias of studies. RESULTS: We found 104 citations in our extensive research. Four articles were ultimately included in the meta-analysis, after excluding 100 reports. All articles were considered low risk of bias in most of the domains assessed in QUADAS-2. We observed that pooled sensitivity and specificity for detecting deep MI were 65% (95% confidence interval [CI] = 54%-75%) and 85% (95% CI = 79%-89%) for MRI, and 71% (95% CI = 63%-78%) and 76% (95% CI = 67%-83%) for TVS, respectively. No statistical differences were found between both imaging techniques (p > 0.05). We observed low heterogeneity for sensitivity and high for specificity regarding TVS; and moderate for both sensitivity and specificity in case of MRI. CONCLUSIONS: The diagnostic performance of TVS and MRI for the evaluation of deep MI in women with low-grade endometrioid endometrial cancer is similar. However, further research is needed as the number of studies is scanty.

A Combined Approach: Laparoscopic Partial Bladder Prior Transurethral Resection for Bladder Endometriosis-Case Report and Surgical Video Presentation.

OBJECTIVE: Bladder endometriosis is the presence of stroma and endometrial glands in the thickness of the detrusor muscle. The main symptoms it produces are dysuria and hematuria whose intensity is directly proportional to the size of the nodule. It is a difficult entity to diagnose for which physical examination is essential. Treatment can be medical, with hormonal therapies, or surgical by transurethral resection of the nodule and laparoscopic partial cystectomy. METHODS: To show a clinical case and review the literature about the technique used. RESULTS: A 29-year-old patient diagnosed with bladder endometriosis in which a combined approach was decided by laparoscopic partial cystectomy after transurethral resection: the patient came to our office for chronic pelvic pain, dysuria, dysmenorrhea, and a physical examination that showed a painful nodule on the anterior side of the vagina. A transvaginal ultrasound, magnetic resonance imaging, and cystoscopy confirm the diagnosis of bladder endometriosis. After a review of the literature on the management of this entity, the patient's clinic, and reproductive desires, the combined approach with excellent results was decided. Dysmenorrhea and dysuria disappeared, preserving the fertility of the patient who became pregnant 6 months after the intervention. CONCLUSION: The use of the combined approach allows to reduce the limitations of both techniques separately.

Detection, quantification, and characterization of polystyrene microplastics and adsorbed bisphenol A contaminant using electroanalytical techniques.

The potential applications of electroanalytical techniques for the quantification and size characterization of nonelectroactive polystyrene microplastics is reported, in addition to characterizing the kinetics of adsorption of bisphenol A on these polystyrene microparticles. The individual adsorption events of very diluted polystyrene microparticles dispersions on glassy-carbon microelectrodes produce the blocking of the charge transfer of a mediator (ferrocene-methanol) thus decreasing the current of the recorded chronoamperogram in a stepwise manner. The magnitude of the current steps are in the order of pA values and can be related to the diameter of the plastic microparticles in the size range 0.1 to 10 µm. The frequency of the current steps in the domain time used (120 s) allows to quantify the number concentration of these microparticles in the range 0.005 to 0.500 pM. Electrochemical impedance spectroscopy confirms the adsorption of the polystyrene microplastics on carbon microelectrodes (and to a lesser extent on platinum microelectrodes) under the same experimental conditions as above. On the other hand, the adsorbed microplastics become concentrators of other pollutants found in the environment. The sensitive differential-pulse voltammetry determination of bisphenol A (linear range 0.80-15.00 µM; detection limit 0.24 µM) was used together with a simple separation procedure for studying the adsorption of bisphenol A on polystyrene microparticles. The adsorption capacity (mg of bisphenol A retained per g of the polystyrene microplastics) decreased from approximately 5.7 to 0.8 mg g-1 with increasing dosages of polystyrene microparticles from 0.2 to 1.6 g l-1. The adsorption isotherms were modeled resulting in a monolayer of bisphenol A adsorbed on the microplastics (i.e., best fitted to a Langmuir model).

Proanthocyanidins in Pruning Wood Extracts of Four European Plum (Prunus domestica L.) Cultivars and Their hLDHA Inhibitory Activity.

European plum tree (Prunus domestica L.) is cultivated in many countries for its delicious and nutritive fruit and, accordingly, certain amounts of wood (from pruning works) are generated every year. The main objective of this work was to value this agricultural woody residue, for which the chemical composition of pruning wood extracts from four European plum cultivars was investigated, and the human lactate dehydrogenase A (hLDHA) inhibitory activity of plum wood extracts and pure proanthocyanidins present in those extracts was measured. For the chemical characterization, total phenolic content and DPPH radical-scavenging assays and HPLC-DAD/ESI-MS analyses were performed, the procyanidin (-)-ent-epicatechin-(2α→O→7,4α→8)-catechin (4), the phenolic glucoside (-)-annphenone (3) and the flavan-3-ol catechin (1) being the major components of the wood extracts. Some quantitative and qualitative differences were found among plum cultivars, and the content of proanthocyanidins ranged from 1.51 (cv. 'Claudia de Tolosa') to 8.51 (cv. 'De la Rosa') mg g-1 of dry wood. For the hLDHA inhibitory activity, six wood extracts and six proanthocyanidins were evaluated by a UV spectrophotometric assay, compound 4 showing the highest inhibitory activity (IC50 3.2 µM) of this enzyme involved on the excessive production of oxalate in the liver of patients affected by the rare disease Primary Hyperoxaluria.

Contribution of Outpatient Ultrasound Transvaginal Biopsy and Puncture in the Diagnosis and Treatment of Pelvic Lesions: A Bicenter Study.

BACKGROUND: The use of transvaginal ultrasound guided biopsy and puncture of pelvic lesions is a minimally invasive technique that allows for accurate diagnosis. It has many advantages compared to other more invasive (lower complication rate) or non-invasive techniques (accurate diagnosis). Furthermore, it offers greater availability, it does not radiate, enables the study of pelvic masses accessible vaginally with ultrasound control in real time, and it is possible to use the colour Doppler avoiding puncturing large vessels among others. The main aim of the work is to describe a standardized ambulatory technique and to determine its usefulness. METHODS: This is a retrospective study of ultrasound transvaginal punctures (core needle biopsies and cytologies) and drainages of pelvic lesions performed on an outpatient basis during the last two years. The punctures were made with local anesthesia, under transvaginal ultrasound guidance with an automatic or semi-automatic 18G biopsy needle with a length of 20-25 cm and a penetration depth of 12 or 22 mm. The material obtained was sent for anatomopathological, cytological and/or microbiological study if necessary. RESULTS: A total of 42 women were recruited in two centers. Fifty procedures (nine punctures, seven drains, and 34 biopsies) were performed. In five cases the punction and drain provided clinical relief in benign pelvic masses. Regarding material of the biopsies performed, 15 were vaginal in women previously histerectomized, finding 10 carcinomas, eight were ovarian tumours in advanced stages or peritoneal carcinomatosis obtaining the appropriate histology in each case, seven were suspicious cervical biopsies finding carcinomas in five of them, three were myometrial biopsies including one breast carcinoma metastasis in the miometrium and a benign placental nodule, and a periurethral biopsy was performed on a woman with a history of endometrial cancer confirming recurrence. The pathological diagnosis was satisfactory in all cases, confirming the nature of the lesion (25 malignant-ten vaginal recurrences of previous gynaecological cancers, eight cases of primary ovarian/peritoneal carcinoma, four new diagnosis of cervical malignant masses, one cervical metastasis of lymphoma, one periurethral recurrence of endometrial carcinoma and one recurrence of breast cancer in the myometrium-and 23 benign). The tolerance was excellent and no complications were detected. CONCLUSION: The ambulatory ultrasound transvaginal puncture and drainage technique is useful for obtaining a sample for pathological and microbiological diagnosis with excellent tolerance that can be used to rule out the recurrence of malignant lesions or progression of the disease, diagnose masses not accessible to gynecological exploration (vaginal vault, myometrium or cervix) and for early histologic diagnosis in cases of advanced peritoneal carcinomatosis or ovarian carcinoma as well as drainage and cytological study of cystic pelvic masses.

Oleocanthal supplemented diet improves renal damage and endothelial dysfunction in pristane-induced systemic lupus erythematosus in mice.

Systemic lupus erythematosus (SLE) is a multiorgan disorder with a deregulated immune-inflammatory response. Nutritional therapy has been considered a promising approach to SLE management. Oleocanthal (OLE), the main extra virgin olive oil (EVOO)-derived secoiridoid, has shown to regulate the immune-inflammatory response in various disease contexts; however, its possible beneficial effects on SLE remain unclear. This study sought to evaluate the effects of OLE enriched diet on renal damage and aortic endothelial dysfunction in murine pristane-induced SLE, focusing on the action mechanisms and signaling pathways involved. BALB/c mice were injected with pristane and fed with OLE supplemented diet (0.01 % (w/w)) for six months. Levels of cytokines were measured by ELISA in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and splenocytes. Presence of immunoglobulin G (IgG) and IgM immune complexes were examined by immunofluorescence and immunohistochemistry. Thoracic aortas were used to evaluate endothelial dysfunction. Western blotting was employed to detect signaling pathways and oxidative-inflammatory-related mediators. Dietary OLE supplementation reduced Th1/Th17 pro-inflammatory cytokines production and alleviated renal damage by decreasing immunoglobulin complexes deposition, and inflammation-mediating enzymes expression. The mechanisms underlying these protective effects could be related to the regulation of nuclear factor erythroid 2-related factor 2/Haem oxygenase 1 (Nrf-2/HO-1), mitogen-activated protein kinases (MAPKs), signal transducer and transcription activator of transcription (STAT-3), inflammasome and, nuclear factor kappa B (NF-κB) signaling pathways. Also, dietary OLE improved aortic endothelial dysfunction and vascular reactivity, normalizing endothelial nitric oxide synthase (eNOS) uncoupling, and NADPH oxidase-1 (NOX-1) overexpression. This study shows the immunomodulatory effects of OLE in an in vivo model of SLE by improving renal damage and regulating aortic endothelial dysfunction. These preliminary results provide OLE as a new therapeutic strategy in SLE management.

Proteomic and metabolomic integration reveals the effects of pre-flowering cytokinin applications on central carbon metabolism in table grape berries.

Consumers around the world prefer high quality table grapes. To achieve higher quality traits at ripening, grapevine producers apply different plant growth regulators. The synthetic cytokinin forchlorfenuron N-(2-chloro-4-pyridinyl)-N'-phenylurea (CPPU) is widely used, its effect on grape quality is poorly understood. We hypothesized that the use of CPPU in pre-flowering can lead to changes in the metabolism that affects grape quality at harvest. Therefore, we investigated the role of CPPU applications on the quality of grapes by integrating proteomics and metabolomics. CPPU-treated grapevines showed a significant increase in berry size and firmness. Proteomic analyses indicated that CPPU-treated berries accumulated enzymes associated with carbohydrate metabolism, glycolysis, and tricarboxylic acid (TCA) cycle at harvest. Metabolomic analyses showed shifts in the abundance of compounds associated with carbohydrate metabolism and TCA cycle in CPPU-treated grapes. These findings suggest that CPPU applications modulate central carbon metabolism, improving grape berry quality.

Effects of Oleacein, a New Epinutraceutical Bioproduct from Extra Virgin Olive Oil, in LPS-Activated Murine Immune Cells.

The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 µg/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, IFN-γ, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2/HO-1 axis and the inhibition of JAK/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases.

(-)-Oleocanthal induces death preferentially in tumor hematopoietic cells through caspase dependent and independent mechanisms.

Olive oil is a key component of the highly cardiovascular protective Mediterranean diet. (-)-Oleocanthal (OLC) is one of the most interesting phenolics present in virgin olive oil, and is formed from secoiridoid ligustroside during the processing of olives to yield the oil. Anti-inflammatory and anti-oxidant properties were identified shortly after OLC isolation, followed by the discovery of anti-tumor activities in a few non-hematopoietic cell lineages. Because of the scarcity of tissues potentially targeted by OLC analyzed so far and the unresolved mechanism(s) for OLC anti-tumor properties, we used a panel of 17 cell lines belonging to 11 tissue lineages to carry out a detailed examination of targets and pathways leading to cell growth inhibition and death. We found that OLC inhibits cell proliferation and induces apoptotic death as revealed by sub-G1 cell cycle analyses and Annexin-V staining in all lineages analyzed except lung carcinoma cell lines. Hematopoietic tumor cell lines, untested until now, were the most sensitive to OLC treatment, whereas non-transformed cells were significantly resistant to cell death. The specificity of OLC-mediated caspase activation was confirmed by blocking experiments and the use of transfectants overexpressing anti apoptotic genes. OLC triggers typical mediators of the intrinsic apoptotic pathway such as production of reactive oxygen species and mitochondrial membrane depolarization (Δψm). Complete blockade of caspases, however, did not result in parallel abrogation of Annexin-V staining, thus suggesting that complex mechanisms are involved in triggering OLC-mediated cell death. Our results demonstrate that OLC preferentially targets hematopoietic tumor cell lines and support that cell death is mediated by caspase-dependent and independent mechanisms.

Relationship of thorium, uranium isotopes and uranium isotopic ratios with physicochemical parameters in cenote water from the Yucatán Peninsula.

Uranium (U) and Thorium (Th) concentrations are normally low in the water (<30 and 5 ng mL-1, respectively). However, we performed a direct analysis of 232Th, 234U, 235U and 238U in cenote water from the Yucatán Peninsula using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) as a rapid response technique to perform environmental radioactivity monitoring. Water samples were collected in 2021 from the cenotes and these were certificated by zones (PYNO, PYNE and PYSE) and monitoring depth [surface water (n = 52) and depth water (n = 48)]. Moreover, physicochemical parameters such as pH, electrical conductivity (EC), total dissolved solids (TDS), and temperature were measured in situ. Results obtained were total U and Th levels below permissible for human consumption. However, physicochemical parameters must be considered before use because it is outside the permissible limits in most cenotes. The median concentration value for 234U, 235U, 238U and 232Th in surface + depth water were 0.0001 ng mL-1, 0.0130 ng mL-1, 1.76 ng mL-1, and 0.062 ng mL-1, respectively. In addition, isotopic ratio of 235U/238U in surface + depth water was 0.00730. In addition, the PYNO zone showed a correlation between 232Th with EC and TDS. The PYSE zone showed a correlation between 232Th and temperature, and 235U/234U with pH, while PYEN did not show correlations. In conclusion, the first time evaluated U isotope concentrations and isotopic ratios of U and 232Th in cenote water from the Yucatán Peninsula, where U and Th concentrations were found below the permissible limits mentioned by guidelines for drinking-water quality. The average of 235U/238U is similar to isotopic ratios in "natural" water.