Antimicrobial Activity of Methylene Blue Associated with Photodynamic Therapy: In Vitro Study in Multi-Species Oral Biofilm.

The control of infectious diseases caused by biofilms is a continuing challenge for researchers due to the complexity of their microbial structures and therapeutic implications. Photodynamic therapy as an adjunctive anti-infective treatment has been described as a possible valid approach but has not been tested in polymicrobial biofilm models. This study evaluated the effect of photodynamic therapy in vitro with methylene blue (MB) 0.01% and red LEDs (λ = 660 nm, power density ≈ 330 mW/cm2, 2 mm distance from culture) on the metabolic activity and composition of a multispecies subgingival biofilm. Test Groups LED and MB + LED showed a more significant reduction in metabolic activity than the non-LED application group (~50 and 55%, respectively). Groups LED and MB equally affected (more than 80%) the total bacterial count in biofilms. No differences were noted in the bacterial biofilm composition between the groups. In vitro LED alone or the MB + LED combination reduced the metabolic activity of bacteria in polymicrobial biofilms and the total subgingival biofilm count.

Erratum: Reconfigurations in brain networks upon awakening from slow wave sleep: Interventions and implications in neural communication.

[This corrects the article DOI: 10.1162/netn_a_00272.].

Exploring genetic testing requests, genetic alterations and clinical associations in a cohort of children with autism spectrum disorder.

Several studies show great heterogeneity in the type of genetic test requested and in the clinicopathological characteristics of patients with ASD. The following study aims, firstly, to explore the factors that might influence professionals' decisions about the appropriateness of requesting genetic testing for their patients with ASD and, secondly, to determine the prevalence of genetic alterations in a representative sample of children with a diagnosis of ASD. Methods: We studied the clinical factors associated with the request for genetic testing in a sample of 440 children with ASD and the clinical factors of present genetic alterations. Even though the main guidelines recommend genetic testing all children with an ASD diagnosis, only 56% of children with an ASD diagnosis were genetically tested. The prevalence of genetic alterations was 17.5%. These alterations were more often associated with intellectual disability and dysmorphic features. There are no objective data to explicitly justify the request for genetic testing, nor are there objective data to justify requesting one genetic study versus multiple studies. Remarkably, only 28% of males were genetically tested with the recommended tests (fragile X and CMA). Children with dysmorphic features and organic comorbidities were more likely to be genetic tested than those without. Previous diagnosis of ASD (family history of ASD) and attendance at specialist services were also associated with Genetically tested Autism Spectrum Disorder GTASD. Our findings emphasize the importance of establishing algorithms to facilitate targeted genetic consultation for individuals with ASD who are likely to benefit, considering clinical phenotypes, efficiency, ethics, and benefits.

Optical and Electrochemical Properties of a Nanostructured ZnO Thin Layer Deposited on a Nanoporous Alumina Structure via Atomic Layer Deposition.

This study explores the optical and electrochemical properties of a ZnO coating layer deposited on a nanoporous alumina structure (NPAS) for potential multifunctional applications. The NPAS, synthesized through an electrochemical anodization process, displays well-defined nanochannels with a high aspect ratio (~3000). The ZnO coating, achieved via atomic layer deposition, enables the tuning of the pore diameter and porosity of the NPAS, thereby influencing both the optical and electrochemical interfacial properties. A comprehensive characterization using photoluminescence, spectroscopy ellipsometry and impedance spectroscopy (with the sample in contact with NaCl solutions) provides insights into optical and electrochemical parameters, including the refractive index, absorption coefficient, and electrolyte-ZnO/NPAS interface processes. This research demonstrates potential for tailoring the optical and interfacial properties of nanoporous structures by selecting appropriate coating materials, thus opening avenues for their utilization in various technological applications.

Impact of Incomplete Revascularization After PCI in Left Main Disease: The EXCEL Trial.

BACKGROUND: The importance of complete revascularization after percutaneous coronary intervention (PCI) in patients with left main coronary artery disease is uncertain. We investigated the clinical impact of complete revascularization in patients with left main coronary artery disease undergoing PCI in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). METHODS: Composite rates of death or myocardial infarction (MI) following PCI during 5-year follow-up were examined in 903 patients based on core laboratory definitions of anatomic and functional complete revascularization, residual SYNTAX score (The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), and residual Jeopardy Score (rJS). RESULTS: The risk of death or MI did not vary based on anatomic, functional, or residual SYNTAX score complete revascularization but did differ according to the rJS (5-year rates 17.6%, 19.5%, and 38.9% with rJS 0, 2, and ≥4, respectively; P=0.006). The higher rate of death or MI with rJS≥4 versus rJS≤2 was driven conjointly by increased mortality (adjusted hazard ratio, 2.29 [95% CI, 1.11-4.71]; P=0.02) and spontaneous MI (adjusted hazard ratio, 2.89 [95% CI, 1.17-7.17]; P=0.02). The most common location for untreated severe stenoses in the rJS≥4 group was the left circumflex artery (LCX), and the post-PCI absence, compared with the presence, of any untreated lesion with diameter stenosis ≥70% in the LCX was associated with reduced 5-year rates of death or MI (18.9% versus 35.2%; hazard ratio, 0.48 [95% CI, 0.32-0.74]; P<0.001). The risk was the highest for residual ostial/proximal LCX lesions. CONCLUSIONS: Among patients undergoing PCI in EXCEL trial, incomplete revascularization according to the rJS was associated with increased rates of death and spontaneous MI. Post-PCI untreated high-grade lesions in the LCX (especially the ostial/proximal LCX) drove these outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01205776.

Fluorescein videoangiography (FL-VAG) as a predictor of cerebral bypass patency.

Background: The fluorescein videoangiography (FL-VAG) has become a valuable adjunct tool in vascular neurosurgery. This work describes using the FL-VAG during bypass surgery and proposes a classification method for evaluating surgical results. Methods: We analyzed 26 patients with 50 cerebral bypasses from September 2018 to September 2022. We used a three grades classification method based on the pass of intravenous fluorescein through the anastomosis. Grade 1 represents the synchronous and total filling of the "T" shape ("green T″) formed by the donor and recipient vessel, Grade 2, the asynchronous filling of the anastomosis (incomplete/asynchronous "green T″), and Grade 3, a non-patent anastomosis (absence of "green T″). Results: Of the 26 patients, 8 underwent one bypass, 14 underwent double bypass, 2 underwent three bypasses, and 2 underwent four bypasses in two different interventions. The type of bypass was end-to-side anastomosis in 47 (94%) cases, internal maxillary artery to middle cerebral artery bypass with a radial artery graft (IMax-MCA anastomosis) in 2 (4%), and PICA-VA transposition in one (2%). We made 24 (48%) bypasses on the right side and 26 (52%) on the left side. After the initial surgery, thirty-nine (78%) bypasses were considered as Grade 1, 5 (10%) as Grade 2, and 6 (12%) as Grade 3. After intraoperative bypass patency assessment (IBPA), 45 (90%) of the bypasses were considered Grade 1 and remained patent on CTA. Conclusions: Using FL-VAG and a three-tier classification method is a reliable tool to predict bypass patency. It is safe, low-risk, and available worldwide.

X-Ray Crystallography for Macromolecular Complexes.

X-ray crystallography has for most of the last century been the standard technique to determine the high-resolution structure of biological macromolecules, including multi-subunit protein-protein and protein-nucleic acids as large as the ribosome and viruses. As such, the successful application of X-ray crystallography to many biological problems revolutionized biology and biomedicine by solving the structures of small molecules and vitamins, peptides and proteins, DNA and RNA molecules, and many complexes-affording a detailed knowledge of the structures that clarified biological and chemical mechanisms, conformational changes, interactions, catalysis and the biological processes underlying DNA replication, translation, and protein synthesis. Now reaching well into the first quarter of the twenty-first century, X-ray crystallography shares the structural biology stage with cryo-electron microscopy and other innovative structure determination methods, as relevant and central to our understanding of biological function and structure as ever. In this chapter, we provide an overview of modern X-ray crystallography and how it interfaces with other mainstream structural biology techniques, with an emphasis on macromolecular complexes.

Walkability and socio-economic status in relation to walking, playing and sports practice in a representative Spanish sample of youth: The PASOS study.

PURPOSE: Physical activity (PA) provides multiple health-related benefits in children and adolescents, however, at present, the majority of young people are insufficiently physically active. The aim of this study was to evaluate if neighborhood walkability and/or socio-economic status (SES) could affect the practice of walking, play outdoors and sports practice in a representative sample of Spanish children and adolescents. METHODS: A sample of 4092 youth (aged 8-16 years old) from 245 primary and secondary schools in 121 localities from each of the 17 Spanish autonomous communities participated in the study. Walk Score was used to evaluate walkability of the neighborhood and household income was used as an indicator of SES. A 7-item self-reported validated questionnaire, was used to assess PA levels, and in a subsample of 10% of the participants, randomly selected from the entire sample, PA was objectively measured by accelerometers. RESULTS: Youth from more walkable areas reported more minutes walking per day compared with those from less walkable neighborhoods (51.4 vs 48.8 minutes, respectively). The lowest average minutes spent in playing outdoors was found among participants from low-SES and low-walkable neighborhoods. Neighborhood SES influenced on the participation in team sports during the weekend, being this participation higher in high SES neighborhoods. CONCLUSION: Providing high walkable environments seems a good strategy to promote PA regardless SES levels. It seems that improving the walkability is a key component to partially overcome the SES inequalities, especially in urban areas with low SES. High-SES environments can offer better sports facilities and more organized physical activities than low-SES ones.

A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis.

Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/µL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

A Combination of a Dopamine Receptor 2 Agonist and a Kappa Opioid Receptor Antagonist Synergistically Reduces Weight in Diet-Induced Obese Rodents.

As the global obesity rate increases, so does the urgency to find effective anti-obesity drugs. In the search for therapeutic targets, central nervous system (CNS) mechanisms engaged in the regulation of energy expenditure and food intake, such as the opioid and dopamine systems, are crucial. In this study, we examined the effect on body weight of two drugs: bromocriptine (BC), a D2R receptor agonist, and PF-04455242, a selective κ opioid receptor (KOR) antagonist. Using diet-induced obese (DIO) rats, we aimed to ascertain whether the administration of BC and PF-04455242, independently or in combination, could enhance body weight loss. Furthermore, the present work demonstrates that the peripheral coadministration of BC and PF-04455242 enhances the reduction of weight in DIO rats and leads to a decrease in adiposity in a food-intake-independent manner. These effects were based on heightened energy expenditure, particularly through the activation of brown adipose tissue (BAT) thermogenesis. Overall, our findings indicate that the combination of BC and PF-04455242 effectively induces body weight loss through increased energy expenditure by increasing thermogenic activity and highlight the importance of the combined use of drugs to combat obesity.

Prevalencia de quejas subjetivas de memoria: estudio poblacional en España / Prevalence of subjective memory complaints: Population study in Spain

Introducción Las quejas subjetivas de memoria (QSM) pueden ser una señal inicial de un posterior deterioro de las funciones cognitivas. Sin embargo, no se han publicado estudios poblacionales cubriendo toda España para conocer la prevalencia de las QSM. El objetivo del presente estudio fue conocer la prevalencia de las QSM en la población general residente en España >50 años y, también qué actuaciones se llevaban a cabo al respecto. Materiales y métodos Se realizaron entrevistas mediante un cuestionario online/Computer Assisted Web Interview (CAWI) a una muestra representativa a nivel nacional >50 años. La encuesta constaba de 34 ítems divididos en 2 bloques. Se consideró presencia de QSM cuando en la pregunta 1 el sujeto contestaba que ‘Sí’ tenía algún problema de memoria. Resultados Se entrevistó a 2.300 personas (53,7% mujeres; 23,9% ≥75 años). El 31% contestaron que consideraban que tenían un problema de memoria (sin diferencias entre sexos, media de tiempo con problemas de memoria de 3,0 años). Se observó mayor prevalencia de QSM en ≥75 años (44%). El 90% no incluían ningún alimento específico en su dieta para sus problemas de memoria, y tampoco estaban tomando productos farmacéuticos, complementos de la dieta o suplementos nutricionales (92%). El 78% de los entrevistados con QSM no han consultado a profesionales sanitarios por sus problemas de memoria. Conclusiones Las QSM tienen una prevalencia considerable en nuestro medio, afectando a casi un tercio de los individuos >50 años. La mayoría de los entrevistados con quejas de memoria no buscó el consejo/recomendación de profesionales sanitarios con respecto a las mismas. (AU)

Introduction Subjective memory complaints (SMC) might be an early sign of further deterioration in cognitive functions. However, no population studies have been published covering all Spain to determine the SMC prevalence. The objective of the present study was to determine the SMC prevalence in the general population residing in Spain >50 years of age and also which related actions were done. Materials and methods Interviews were conducted with a nationally representative sample >50 years of age using an online/computer assisted web interview (CAWI) questionnaire. The survey consisted of 34 items divided into two blocks. Presence of SMC was considered when in question 1 the subject answered that “Yes” he had some memory problem. Results Two thousand three hundred people (53.7% women; 23.9% ≥75 years old) were interviewed. 31% answered that they considered they had a memory problem (no differences between sexes, mean time with memory problems of 3.0 years). A higher prevalence of SMC was observed in ≥75 years old (44%). 90% did not include any specific foods in their diet for their memory problems, neither were taking any pharmaceuticals, diet supplements or nutritional supplements (92%). 78% of those interviewed with SMC have not consulted health professionals for their memory problems. Conclusions SMC are considerably prevalent in our environment affecting almost a third of people ≥50 years of age. Most of the interviewees with SMC did not go to health professionals to manage their SMC. (AU)

Prevalencia de quejas subjetivas de memoria: estudio poblacional en España / Prevalence of subjective memory complaints: Population study in Spain

Introducción Las quejas subjetivas de memoria (QSM) pueden ser una señal inicial de un posterior deterioro de las funciones cognitivas. Sin embargo, no se han publicado estudios poblacionales cubriendo toda España para conocer la prevalencia de las QSM. El objetivo del presente estudio fue conocer la prevalencia de las QSM en la población general residente en España >50 años y, también qué actuaciones se llevaban a cabo al respecto. Materiales y métodos Se realizaron entrevistas mediante un cuestionario online/Computer Assisted Web Interview (CAWI) a una muestra representativa a nivel nacional >50 años. La encuesta constaba de 34 ítems divididos en 2 bloques. Se consideró presencia de QSM cuando en la pregunta 1 el sujeto contestaba que ‘Sí’ tenía algún problema de memoria. Resultados Se entrevistó a 2.300 personas (53,7% mujeres; 23,9% ≥75 años). El 31% contestaron que consideraban que tenían un problema de memoria (sin diferencias entre sexos, media de tiempo con problemas de memoria de 3,0 años). Se observó mayor prevalencia de QSM en ≥75 años (44%). El 90% no incluían ningún alimento específico en su dieta para sus problemas de memoria, y tampoco estaban tomando productos farmacéuticos, complementos de la dieta o suplementos nutricionales (92%). El 78% de los entrevistados con QSM no han consultado a profesionales sanitarios por sus problemas de memoria. Conclusiones Las QSM tienen una prevalencia considerable en nuestro medio, afectando a casi un tercio de los individuos >50 años. La mayoría de los entrevistados con quejas de memoria no buscó el consejo/recomendación de profesionales sanitarios con respecto a las mismas. (AU)

Introduction Subjective memory complaints (SMC) might be an early sign of further deterioration in cognitive functions. However, no population studies have been published covering all Spain to determine the SMC prevalence. The objective of the present study was to determine the SMC prevalence in the general population residing in Spain >50 years of age and also which related actions were done. Materials and methods Interviews were conducted with a nationally representative sample >50 years of age using an online/computer assisted web interview (CAWI) questionnaire. The survey consisted of 34 items divided into two blocks. Presence of SMC was considered when in question 1 the subject answered that “Yes” he had some memory problem. Results Two thousand three hundred people (53.7% women; 23.9% ≥75 years old) were interviewed. 31% answered that they considered they had a memory problem (no differences between sexes, mean time with memory problems of 3.0 years). A higher prevalence of SMC was observed in ≥75 years old (44%). 90% did not include any specific foods in their diet for their memory problems, neither were taking any pharmaceuticals, diet supplements or nutritional supplements (92%). 78% of those interviewed with SMC have not consulted health professionals for their memory problems. Conclusions SMC are considerably prevalent in our environment affecting almost a third of people ≥50 years of age. Most of the interviewees with SMC did not go to health professionals to manage their SMC. (AU)

Optimizing parameter search for community detection in time-evolving networks of complex systems.

Network representations have been effectively employed to analyze complex systems across various areas and applications, leading to the development of network science as a core tool to study systems with multiple components and complex interactions. There is a growing interest in understanding the temporal dynamics of complex networks to decode the underlying dynamic processes through the temporal changes in network structures. Community detection algorithms, which are specialized clustering algorithms, have been instrumental in studying these temporal changes. They work by grouping nodes into communities based on the structure and intensity of network connections over time, aiming to maximize the modularity of the network partition. However, the performance of these algorithms is highly influenced by the selection of resolution parameters of the modularity function used, which dictate the scale of the represented network, in both size of communities and the temporal resolution of the dynamic structure. The selection of these parameters has often been subjective and reliant on the characteristics of the data used to create the network. Here, we introduce a method to objectively determine the values of the resolution parameters based on the elements of self-organization and scale-invariance. We propose two key approaches: (1) minimization of biases in spatial scale network characterization and (2) maximization of scale-freeness in temporal network reconfigurations. We demonstrate the effectiveness of these approaches using benchmark network structures as well as real-world datasets. To implement our method, we also provide an automated parameter selection software package that can be applied to a wide range of complex systems.

Interobserver variability in thyroid ultrasound.

PURPOSE: Ultrasound evaluation of thyroid nodules is the preferred technique, but it is dependent on operator interpretation, leading to inter-observer variability. The current study aimed to determine the inter-physician consensus on nodular characteristics, risk categorization in the classification systems, and the need for fine needle aspiration puncture. METHODS: Four endocrinologists from the same center blindly evaluated 100 ultrasound images of thyroid nodules from 100 different patients. The following ultrasound features were evaluated: composition, echogenicity, margins, calcifications, and microcalcifications. Nodules were also classified according to ATA, EU-TIRADS, K-TIRADS, and ACR-TIRADS classifications. Krippendorff's alpha test was used to assess interobserver agreement. RESULTS: The interobserver agreement for ultrasound features was: Krippendorff's coefficient 0.80 (0.71-0.89) for composition, 0.59 (0.47-0.72) for echogenicity, 0.73 (0.57-0.88) for margins, 0.55 (0.40-0.69) for calcifications, and 0.50 (0.34-0.67) for microcalcifications. The concordance for the classification systems was 0.7 (0.61-0.80) for ATA, 0.63 (0.54-0.73) for EU-TIRADS, 0.64 (0.55-0.73) for K-TIRADS, and 0.68 (0.60-0.77) for K-TIRADS. The concordance in the indication of fine needle aspiration puncture (FNA) was 0.86 (0.71-1), 0.80 (0.71-0.88), 0.77 0.67-0.87), and 0.73 (0.64-0.83) for systems previously described respectively. CONCLUSIONS: Interobserver agreement was acceptable for the identification of nodules requiring cytologic study using various classification systems. However, limited concordance was observed in risk stratification and many ultrasonographic characteristics of the nodules.

Factors intrinsic to handling and transport in pre-slaughter behavioural changes in beef cattle.

The aim of this study was to evaluate handling and transport variables as potential causes of disturbed behaviour in response to seeing a person on an overhead observation platform during pre-slaughter in batches of females and castrated males composed of pure or crossed Bos Taurus animals (Aberdeen Angus, Red Angus, Hereford and Charolais) with a maximum of 37.5% Bos indicus, and maturity at slaughter varying from zero to eight teeth, coming from pasture and confined systems. For the batches of castrated males, the independent variables included the distance covered on the trip, and the handling and facilities on the farms. For the female batches, the variables were travel time and waiting time prior to unloading. For both sexes, the presence of horns in the batches and the load density were included in the regression equations. Disturbed behaviour, the result of factors related to animal handling and transportation, is detrimental to satisfactory results in production systems. It is up to the managers in the production chain to seek alternatives in order to minimise inappropriate behaviour, which is one determinant of loss. Handling and transport are determining factors in the behaviour of beef cattle during the pre-slaughter period.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Cardiovascular risk assessment in inflammatory bowel disease with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has been reported to increase the risk of early atherosclerosis even in young patients. Moreover, metabolic dysfunction-associated steatotic liver disease (MASLD), which has been linked to IBD, is a well-recognized but underdiagnosis entity related to cardiovascular risk. We analyze the impact of MASLD in IBD patients' cardiovascular risk through both advanced lipoprotein profile sorted by nuclear magnetic resonance spectroscopy, and carotid artery intima-media thickness (CIMT). METHODS: Cross-sectional cohort study which involves 941 IBD adult outpatients. Of them, 50 patients with IBD who met criteria for MASLD and 50 with IBD without MASLD, matched by sex and age were included. Alterations in CIMT were evaluated considering abnormal measures above the 75th percentile adjusted for sex and age. Specific advanced lipoprotein profile was also carried out. RESULTS: Most of the patients had an abnormal CIMT (58%). MASLD (OR=5.05, CI 95%=1.71-14.92) and female sex (OR=3.32, CI 95%=1.03-10) were significantly associated with CIMT alterations. Dense LDL particles (with high cholesterol composition in general cohort (OR=3.62, 95% CI=1.07-12.19) and high triglycerides density in young subgroup (OR=6.25, 95% CI=1.04-50) but not total LDL cholesterol were associated with CIMT alterations. CONCLUSIONS: MASLD and female sex are associated with early atherosclerosis in IBD patients. Dense LDL particle in combination with vascular imaging findings should be evaluated as non-invasive tools in the management of cardiovascular risk in IBD patients.

Anticancer Activity of Sargassum fluitans Extracts in Different Cancer Cells.

BACKGROUND: The arrival of large quantities of Sargassum in the Mexican Caribbean Sea has generated major environmental, health and economic problems. Although Sargassum has been used in the generation of some commercial products, few studies have described its possible applications as a source of compounds with anticancer activity. OBJECTIVE: This study aimed to evaluate the antiproliferative effects of different Sargassum extracts on various cancer cell lines. Furthermore, LC/QTOF-MS was used to identify the compounds related to the antiproliferative effect. METHODS: First, determination of the seaweed was performed, and dichloromethane, chloroform and methanol extracts were obtained. The extracts were evaluated for their antiproliferative effects by MTT in breast (MDAMB- 231 and MCF-7), prostate (DU-145), lung (A549) and cervical (SiHa) cancer cell lines. Finally, LC/QTOFMS identified the compounds related to the antiproliferative effect. RESULTS: The authentication showed Sargassum fluitans as the predominant species. The extracts of dichloromethane and chloroform showed an antiproliferative effect. Interestingly, the fractionation of the chloroform extract showed two fractions (FC1 and FC2) with antiproliferative activity in MDA-MB-231, SiHa and A549 cancer cell lines. On the other hand, three fractions of dichloromethane extract (FD1, FD4 and FD5) also showed antiproliferative effects in the MDA-MB-231, MCF-7, SiHa and DU-145 cancer cell lines. Furthermore, LC/QTOF-MS revealed the presence of eight major compounds in FC2. Three compounds with evidence of anticancer activity were identified (D-linalool-3-glucoside, (3R,4S,6E,10Z)-3,4,7,11-tetramethyl-6,10-tridecadienal and alpha-tocotrienol). CONCLUSION: These findings showed that Sargassum fluitans extracts are a possible source of therapeutic agents against cancer and could act as scaffolds for new drug discovery.

Identification of MCM4 and PRKDC as new regulators of osteosarcoma cell dormancy based on 3D cell cultures.

Dormancy is a potential way for tumors to develop drug resistance and escape treatment. However, the mechanisms involved in cancer dormancy remain poorly understood. This is mainly because there is no in vitro culture model making it possible to spontaneously induce dormancy. In this context, the present work proposes the use of three-dimensional (3D) spheroids developed from osteosarcoma cell lines as a relevant model for studying cancer dormancy. MNNG-HOS, SaOS-2, 143B, MG-63, U2OS and SJSA-1 cell lines were cultured in 3D using the Liquid Overlay Technique (LOT). Dormancy was studied by staining cancer cells with a lipophilic dye (DiD), and long-term DiD+ cells were considered as dormant cancer cells. The role of the extracellular matrix in inducing dormancy was investigated by embedding cells into methylcellulose or Geltrex™. Gene expression of DiD+ cells was assessed with a Nanostring™ approach and the role of the genes detected in dormancy was validated by a transient down-expression model using siRNA treatment. Proliferation was measured using fluorescence microscopy and the xCELLigence technology. We observed that MNNG-HOS, 143B and MG-G3 cell lines had a reduced proliferation rate in 3D compared to 2D. U2OS cells had an increased proliferation rate when they were cultured in Geltrex™ compared to other 3D culture methods. Using 3D cultures, a transcriptomic signature of dormancy was obtained and showed a decreased expression of 18 genes including ETV4, HELLS, ITGA6, MCM4, PRKDC, RAD21 and UBE2T. The treatment with siRNA targeting these genes showed that cancer cell proliferation was reduced when the expression of ETV4 and MCM4 were decreased, whereas proliferation was increased when the expression of RAD21 was decreased. 3D culture facilitates the maintenance of dormant cancer cells characterized by a reduced proliferation and less differential gene expression as compared to proliferative cells. Further studies of the genes involved has enabled us to envisage their role in regulating cell proliferation.