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Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

In this work, silver nanoparticles (AgNPs) were elaborated using a simple, low-cost, and reproducible method by thermal treatment at 90°C of chitooligosaccharides (COSs), produced by chitosan depolymerization using the digestives chitosanases from Portunus segnis viscera, in the presence of AgNO3. The characterization of the obtained AgNPs, using UV–visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared (FTIR) spectroscopy analyses, showed that they are crystalline, spherical and stable for a month at 4°C. Moreover, the biological properties of the synthesized AgNPs were evaluated, proving that they exhibited interesting antioxidant and antibacterial activities. The present investigation suggested that COSs will be a good source for the preparation of AgNPs that could be useful in different industrial and biomedical applications.

IntroductionFibroblast growth factor 20 (Fgf20), a member of the Fgf9 subfamily, was identified as an important regulator of bone differentiation and homeostasis processes. However, the role of Fgf20 in bone physiology has not been approached yet. Here we present a comprehensive bone phenotype analysis of mice with functional ablation of Fgf20.MethodsThe study conducts an extensive analysis of Fgf20 knockout mice compared to controls, incorporating microCT scanning, volumetric analysis, Fgf9 subfamily expression and stimulation experiment and histological evaluation.ResultsThe bone phenotype could be detected especially in the area of​ the lumbar and caudal part of the spine and in fingers. Regarding the spine, Fgf20-/- mice exhibited adhesions of the transverse process of the sixth lumbar vertebra to the pelvis as well as malformations in the distal part of their tails. Preaxial polydactyly and polysyndactyly in varying degrees of severity were also detected. High resolution microCT analysis of distal femurs and the fourth lumbar vertebra showed significant differences in structure and mineralization in both cortical and trabecular bone. These findings were histologically validated and may be associated with the expression of Fgf20 in chondrocytes and their progenitors. Moreover, histological sections demonstrated increased bone tissue formation, disruption of Fgf20-/- femur cartilage, and cellular-level alterations, particularly in osteoclasts. We also observed molar dysmorphology, including root taurodontism, and described variations in mineralization and dentin thickness.DiscussionOur analysis provides evidence that Fgf20, together with other members of the Fgf9 subfamily, plays a crucial regulatory role in skeletal development and bone homeostasis.

Background: It has been suggested that the dysfunction of the gut microbiome can have deleterious effects on the regulation of body weight and adiposity by affecting energy metabolism. In this context, gut bacterial profiling studies have contributed to characterize specific bacteria associated with obesity. This review covers the information driven by gut bacterial profiling analyses and emphasizes the potential application of this knowledge in precision nutrition strategies for obesity understanding and weight loss management. Summary: Gut bacterial profiling studies have identified bacterial families that are more abundant in obese than in nonobese individuals (i.e., Prevotellaeae, Ruminococcaceae, and Veillonellaceae) as well as other families that have been repeatedly found more abundant in nonobese people (i.e., Christensenellaceae and Coriobacteriaceae), suggesting that an increase in their relative amount could be an interesting target in weight-loss treatments. Also, some gut-derived metabolites have been related to the regulation of body weight, including short-chain fatty acids, trimethylamine-N-oxide, and branched-chain and aromatic amino acids. Moreover, gut microbiota profiles may play a role in determining weight loss responses to specific nutritional treatments for the precise management of obesity. Thus, incorporating gut microbiota features may improve the performance of integrative models to predict weight loss outcomes. Key Messages: The application of gut bacterial profiling information is of great value for precision nutrition in metabolic diseases since it contributes to the understanding of the role of the gut microbiota in obesity onset and progression, facilitates the identification of potential microorganism targets, and allows the personalization of tailored weight loss diets as well as the prediction of adiposity outcomes based on the gut bacterial profiling of each individual. Integrating microbiota information with other omics knowledge (genetics, epigenetics, transcriptomics, proteomics, and metabolomics) may provide a more comprehensive understanding of the molecular and physiological events underlying obesity and adiposity outcomes for precision nutrition.

Background: Edible plants have been linked to the mitigation of metabolic disturbances in liver and adipose tissue, including the decrease of lipogenesis and the enhancement of lipolysis and adipocyte browning. In this context, plant microRNAs could be key bioactive molecules underlying the cross-kingdom beneficial effects of plants. This study sought to explore the impact of plant-derived microRNAs on the modulation of adipocyte and hepatocyte genes involved in metabolism and thermogenesis. Methods: Plant miR6262 was selected as a candidate from miRBase for the predicted effect on the regulation of human metabolic genes. Functional validation was conducted after transfection with plant miRNA mimics in HepG2 hepatocytes exposed to free fatty acids to mimic liver steatosis and hMADs cells differentiated into brown-like adipocytes. Results: miR6262 decreases the expression of the predicted target RXRA in the fatty acids-treated hepatocytes and in brown-like adipocytes and affects the expression profile of critical genes involved in metabolism and thermogenesis, including PPARA, G6PC, SREBF1 (hepatocytes) and CIDEA, CPT1M and PLIN1 (adipocytes). Nevertheless, plant miR6262 mimic transfections did not decrease hepatocyte lipid accumulation or stimulate adipocyte browning. Conclusions: these findings suggest that plant miR6262 could have a cross-kingdom regulation relevance through the modulation of human genes involved in lipid and glucose metabolism and thermogenesis in adipocytes and hepatocytes.

Inulin is a plant polysaccharide which, due to its chemical structure, is not digestible by human gut enzymes but by some bacteria of the human microbiota, acting as a prebiotic. Consequently, inulin consumption has been associated with changes in the composition of the intestinal microbiota related to an improvement of the metabolic state, counteracting different obesity-related disturbances. However, the specific mechanisms of action, including bacterial changes, are not exactly known. Here, a bibliographic review was carried out to study the main effects of inulin on human metabolic health, with a special focus on the mechanisms of action of this prebiotic. Inulin supplementation contributes to body weight and BMI control, reduces blood glucose levels, improves insulin sensitivity, and reduces inflammation markers, mainly through the selective favoring of short-chain fatty acid (SCFA)-producer species from the genera Bifidobacterium and Anaerostipes. These SCFAs have been shown to ameliorate glucose metabolism and decrease hepatic lipogenesis, reduce inflammation, modulate immune activity, and improve anthropometric parameters such as body weight or BMI. In conclusion, the studies collected suggest that inulin intake produces positive metabolic effects through the improvement of the intestinal microbiota and through the metabolites produced by its fermentation.

La pericarditis constrictiva es entendida como el estadio final de un proceso inflamatorio crónico que lleva a la fibrosis, engrosamiento y rigidez pericárdica, provocando la dificultad del llenado ventricular, lo cual caracteriza clínicamente a esta entidad. A pesar de que para el diagnóstico es necesario demostrar repercusión hemodinámica mediante ecocardiografía, en ciertas ocasiones los hallazgos radiológicos de la tomografía computarizada son reveladores y permiten orientar de forma correcta a los pacientes. El paciente presentado consultó por un aumento de su disnea habitual, y en plena época epidemiológica de COVID-19 no se sospechó de estar ante otra entidad.

Objectives: The aim of this study was to determine the degree of integration of patient safety in the training of medical faculties at universities in Spain.Methods: A descriptive, cross-sectional study was conducted. An assessment was made of the curse syllabi of Spanish medical schools, summarizing the proportion of faculties that present each of the topics recommended in the WHO’s curriculum guide.Results: Of the 49 faculties, access to the curse syllabus of the subjects for the academic year 2023-2024 was obtained from 38 (78%). Although 82% of the faculties integrated some patient safety topic, only 56% included between 1 and 3 of the 11 topics recommended by WHO. The maximum number of integrated topics was 7, and this was only achieved by 1 faculty.Conclusion: There is progress in the incorporation of fundamental concepts in patient safety, but the comprehensive implementation of all topics recommended by the WHO in Spanish medical schools is insufficient.

Abstract There are many surgical techniques (packing, Pringle maneuver, etc.) and hemostatic agents to manage hepatic bleeding in trauma surgery. This study compares the effectiveness of two different types of hemostatic agents, one is an active flowable hemostat and the other is a passive hemostat made of modified absorbable polymers [MAP]. Both surgical technique and hemostatic agents can be used together as a means of controlling bleeding. We have hypothesized that a single hemostatic agent might be as effective as a unique hemostatic surgical technique. Twenty swine were prospectively randomized to receive either active Flowable (Floseal) or passive MAP powder (PerClot) hemostatic agents. We used a novel severe liver injury model that caused exsanguinating hemorrhage. The main outcome measure was total blood loss volume. The total volume of blood loss, from hepatic injury to minute 120, was significantly lower in the Flowable group (407.5 cm3; IqR: 195.0–805.0 cm3) compared to MAP group (1107.5 cm3; IqR: 822.5 to 1544.5 cm3) (Hodges–Lehmann median difference: − 645.0 cm3; 95% CI: − 1144.0 to − 280.0 cm3; p = 0.0087). The rate of blood loss was significantly lower in the flowable group compared with the MAP group as measured from time of injury to minutes 3, 9, 12, and 120 (except for 6 min). The mean arterial pressure gradually recovered in the flowable group by 24 h, whereas in the MAP group, the mean arterial pressure was consistently stayed below baseline values. Kaplan–Meier survival analysis indicated similar rates of death between study groups (Logrank test p = 0.3395). Both the flowable and the MAP hemostatic agents were able to effectively control surgical bleeding in a novel severe liver injury model, however, the flowable gelatin–thrombin agent provided quicker and better bleed control.

Cancer and bacterial infections rank among the most significant global health threats. accounting for roughly 25 million fatalities each year. This statistic underscores the urgent necessity for developing novel drugs, enhancing current treatments, and implementing systems that boost their bioavailability to achieve superior therapeutic outcomes. Liposomes have been recognised as effective carriers; nonetheless, they encounter issues with long-term stability and structural integrity, which limit their pharmaceutical applicability. Chitosomes (chitosan-coated liposomes) are generally a good alternative to solve these issues. This research aims to demonstrate the effective individual encapsulation of ciprofloxacin (antibacterial, hydrophilic) and etoposide (anticancer, hydrophobic), within chitosomes to create more effective drug delivery systems (oral administration for ciprofloxacin, parenteral administration for etoposide). Thus, liposomes and chitosomes were prepared using the thin-film hydration technique and were characterised through ATR-FTIR, Dynamic Light Scattering (DLS), zeta potential, and release profiling. In both cases, the application of chitosomes enhanced long-term stability in size and surface charge. Chitosome-encapsulated ciprofloxacin formulations exhibited a slower and sustained release profile, while the combined effect of etoposide and chitosan showed heightened efficacy against the glioblastoma cell line U373. Therefore, coating liposomes with chitosan improved the encapsulation system’s properties, resulting in a promising method for drug delivery.

The use of natural-origin biomaterials in bioengineering has led to innovative approaches in agroforestry. Bacterial cellulose (BC), sharing the same chemical formula as plant-origin cellulose (PC), exhibits significantly different biochemical properties, including a high degree of crystallinity and superior water retention capacity. Previous research showed that natural-origin glucose-based chitin enhanced plant growth in both herbaceous and non-herbaceous plants. In this study, we produced BC in the laboratory and investigated its effects on the substrate and on Solanum lycopersicum seedlings. Soil amended with BC increased root growth compared with untreated seedlings. Additionally, under limited irrigation conditions, BC increased global developmental parameters including fresh and dry weight, as well as total carbon and nitrogen content. Under non-irrigation conditions, BC contributed substantially to plant survival. RNA sequencing (Illumina®) on BC-treated seedlings revealed that BC, despite its bacterial origin, did not stress the plants, confirming its innocuous nature, and it lightly induced genes related to root development and cell division as well as inhibition of stress responses and defense. The presence of BC in the organic substrate increased soil availability of phosphorus (P), iron (Fe), and potassium (K), correlating with enhanced nutrient uptake in plants. Our results demonstrate the potential of BC for improving soil nutrient availability and plant tolerance to low irrigation, making it valuable for agricultural and forestry purposes in the context of global warming.

Chitin and chitosan, abundant biopolymers derived from the shells of crustaceans and the cell walls of fungi, have garnered considerable attention in pharmaceutical circles due to their biocompatibility, biodegradability, and versatile properties. Deep eutectic solvents (DESs), emerging green solvents composed of eutectic mixtures of hydrogen bond acceptors and donors, offer promising avenues for enhancing the solubility and functionality of chitin and chitosan in pharmaceutical formulations. This review delves into the potential of utilizing DESs as solvents for chitin and chitosan, highlighting their efficiency in dissolving these polymers, which facilitates the production of novel drug delivery systems, wound dressings, tissue engineering scaffolds, and antimicrobial agents. The distinctive physicochemical properties of DESs, including low toxicity, low volatility, and adaptable solvation power, enable the customization of chitin and chitosan-based materials to meet specific pharmaceutical requirements. Moreover, the environmentally friendly nature of DESs aligns with the growing demand for sustainable and eco-friendly processes in pharmaceutical manufacturing. This revision underscores recent advances illustrating the promising role of DESs in evolving the pharmaceutical applications of chitin and chitosan, laying the groundwork for the development of innovative drug delivery systems and biomedical materials with enhanced efficacy and safety profiles.

Abstract Background All health overuse implies an unnecessary risk of patients suffering adverse events (AEs). However, this hypothesis has not been corroborated by direct estimates for inappropriate hospital admission (IHA). The objectives of the study were the following: (1) to analyze the association between IHA and the development of subsequent AEs; (2) to explore the distinct clinical and economic implications of AEs subsequent IHA compared to appropriate admissions. Methods An observational cross-sectional study was conducted on hospitalized patients in May 2019 in a high-complexity hospital in Madrid, Spain. The Appropriateness Evaluation Protocol was used to measure IHA, and the methodologies of the Harvard Medical Practice Study and the European Point Prevalence Survey of Healthcare-associated Infections were used to detect and characterize AEs. The association between IHA and the subsequent. Results A total of 558 patients in the hospital ward were studied. IHA increased the risk of subsequent occurrence of AEs (OR [95% CI]: 3.54 [1.87 to 6.69], versus appropriate) and doubled the mean AEs per patient (coefficient [95% CI]: 0.19 [0.08 to 0.30] increase, versus appropriate) after adjusting for confounders. IHA was a predictive variable of subsequent AEs and the number of AEs per patient. AEs developed after IHA were associated with scheduled admissions (78.9% of AEs, versus 27.9% after appropriate admissions; p

El aumento en el uso de cigarrillos electrónicos ha llevado a la identificación reciente de varios tipos de daños pulmonares, entre los cuales destaca la neumonía lipoidea, que se caracteriza por la presencia de lípidos en los alvéolos. Debido a su presentación clínica inespecífica y a la pobre caracterización de su evolución natural, a menudo se pasa por alto o se retrasa su diagnóstico. El diagnóstico preciso requiere un alto índice de sospecha, que implica tener conocimiento de esta enfermedad y de sus manifestaciones radiológicas, para así posteriormente confirmarlo mediante la demostración de macrófagos cargados de lípidos en muestras de lesiones pulmonares. El objetivo de este artículo es presentar el caso clínico de una paciente con neumonía lipoidea exógena asociada al uso de cigarrillos electrónicos. Con el conocimiento de esta enfermedad y de sus características radiológicas se espera mejorar su diagnóstico y manejo, lo que conllevará mejores resultados para los pacientes.

Abstract Hypoxia develops during the growth of solid tumors and influences tumoral activity in multiple ways. Low oxygen tension is also present in the bone microenvironment where Ewing sarcoma (EwS) – a highly aggressive pediatric cancer – mainly arises. Hypoxia inducible factor 1 subunit alpha (HIF-1-a) is the principal molecular mediator of the hypoxic response in cancer whereas EWSR1::FLI1 constitutes the oncogenic driver of EwS. Interaction of the two proteins has been shown in EwS. Although a growing body of studies investigated hypoxia and HIFs in EwS, their precise role for EwS pathophysiology is not clarified to date. This review summarizes and structures recent findings demonstrating that hypoxia and HIFs play a role in EwS at multiple levels. We propose to view hypoxia and HIFs as independent protagonists in the story of EwS and give a perspective on their potential clinical relevance as prognostic markers and therapeutic targets in EwS treatment.

BackgroundEdible plants can exert anti-inflammatory activities in humans, being potentially useful in the treatment of inflammatory diseases. Plant-derived microRNAs have emerged as cross-kingdom gene expression regulators and could act as bioactive molecules involved in the beneficial effects of some edible plants. We investigated the role of edible plant-derived microRNAs in the modulation of pro-inflammatory human genes.MethodsMicroRNAs from plant-derived foods were identified by next-generation sequencing. MicroRNAs with inflammatory putative targets were selected, after performing in silico analyses. The expression of candidate plant-derived miRNAs was analyzed by qPCR in edible plant-derived foods and their effects were evaluated in THP-1 monocytes differentiated to macrophages. The bioavailability of candidate plant miRNAs in humans was evaluated in feces and serum samples by qPCR.ResultsmiR482f and miR482c-5p are present in several edible plant-derived foods, such as fruits, vegetables, and cooked legumes and cereals, and fats and oils. Transfections with miR482f and miR482c-5p mimics decreased the gene expression of CLEC7A and NFAM1, and TRL6, respectively, in human THP-1 monocytes differentiated to macrophages, which had an impact on gene expression profile of inflammatory biomarkers. Both microRNAs (miR482f and miR482c-5p) resisted degradation during digestion and were detected in human feces, although not in serum.ConclusionOur findings suggest that miR482f and miR482c-5p can promote an anti-inflammatory gene expression profile in human macrophages in vitro and their bioavailability in humans can be achieved through diet, but eventually restricted at the gut level.

Abstract Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.

Introduction Adverse healthcare-related events (AE) entail reduced patient safety. Estimating their frequency, characteristics, avoidability and impact is a means to identify targets for improvement in the quality of care.Methods This was a descriptive observational study conducted within the Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD). The study was conducted in a high-complexity hospital in May 2019 through a two-phase electronic medical record review: (1) AE screening and epidemiological and clinical data collection and (2) AE review and classification and analysis of their impact, avoidability, and associated costs.Results A total of 636 patients were studied. The prevalence of AE was 12.4%. Death during the stay was associated with the presence of AE (OR [CI95%]: 2.15 [1.07 to 4.52]) versus absence and emergency admission (OR [CI95%]: 17.11[6.63 to 46.26]) versus scheduled. A total of 70.2% of the AEs were avoidable. Avoidable AEs were associated with the presence of pressure ulcers (OR [CI95%]: 2.77 [1.39 to 5.51]), central venous catheter (OR [CI95%]: 2.58 [1.33 to 5.00]) and impaired mobility (OR [CI95%]: 2.24[1.35 to 3.71]), versus absences. They were associated too with the stays in the intensive care unit (OR [CI95%]: 2.75 [1.07 to 7.06]) versus medical service. AEs were responsible for additional costs of €909,716.8 for extra days of stay and €12,461.9 per patient with AE.Conclusions The prevalence of AEs was similar to that found in other studies. AEs led to worse patient outcomes and were associated with the patient’s death. Although avoidable AEs were less severe, their higher frequency produced a greater impact on the patient and healthcare system.Key messagesAdverse events are one of the main problems in healthcare delivery and patients who suffer from at least one AE are double as likely to die during hospitalization.Avoidable adverse events are the most frequent in health care and they are a good target where achieve improvement areas that allow getting optimal patient safety and quality of care levels.Patients hospitalized in the ICU, with the previous presence of pressure ulcers, central venous catheter, or impaired mobility were associated with the development of avoidable AE, so optimal management of these patients would reduce the impact of AE.

Abstract Chimeric fusion transcription factors are oncogenic hallmarks of several devastating cancer entities including pediatric sarcomas, such as Ewing sarcoma (EwS) and alveolar rhabdomyosarcoma (ARMS). Despite their exquisite specificity, these driver oncogenes have been considered largely undruggable due to their lack of enzymatic activity. Here, we show in the EwS model that – capitalizing on neomorphic DNA-binding preferences – the addiction to the respective fusion transcription factor EWSR1-FLI1 can be leveraged to express therapeutic genes. We genetically engineered a de novo enhancer-based, synthetic and highly potent expression cassette that can elicit EWSR1-FLI1-dependent expression of a therapeutic payload as evidenced by episomal and CRISPR-edited genomic reporter assays. Combining in silico screens and immunohistochemistry, we identified GPR64 as a highly specific cell surface antigen for targeted transduction strategies in EwS. Functional experiments demonstrated that anti-GPR64-pseudotyped lentivirus harboring our expression cassette can specifically transduce EwS cells to promote the expression of viral thymidine kinase sensitizing EwS for treatment to otherwise relatively non-toxic (Val)ganciclovir and leading to strong anti-tumorigenic, but no adverse effects in vivo. Further, we prove that similar vector designs can be applied in PAX3-FOXO1-driven ARMS, and to express immunomodulatory cytokines, such as IL-15 and XCL1, in tumor entities typically considered to be immunologically ‘cold’. Collectively, these results generated in pediatric sarcomas indicate that exploiting, rather than suppressing, the neomorphic functions of chimeric transcription factors may open inroads to innovative and personalized therapies, and that our highly versatile approach may be translatable to other cancers addicted to oncogenic transcription factors with unique DNA-binding properties.

Plant-based food interventions are promising therapeutic approaches for non-alcoholic fatty liver disease (NAFLD) treatment, and microRNAs (miRNAs) have emerged as functional bioactive components of dietary plants involved in cross-kingdom communication. Deeper investigations are needed to determine the potential impact of plant miRNAs in NAFLD. This study aimed to identify plant miRNAs that could eventually modulate the expression of human metabolic genes and protect against the progression of hepatic steatosis. Plant miRNAs from the miRBase were used to predict human target genes, and miR8126-3p and miR8126-5p were selected as candidates for their potential role in inhibiting glucose and lipid metabolism-related genes. Human HepG2 cells were transfected with plant miRNA mimics and then exposed to a mixture of oleic and palmitic acids to mimic steatosis. miR8126-3p and miR8126-5p transfections inhibited the expression of the putative target genes QKI and MAPKAPK2, respectively, and had an impact on the expression profile of key metabolic genes, including PPARA and SREBF1. Quantification of intrahepatic triglycerides revealed that miR8126-3p and miR8126-5p attenuated lipid accumulation. These findings suggest that plant miR8126-3p and miR8126-5p would induce metabolic changes in human hepatocytes eventually protecting against lipid accumulation, and thus, they could be potential therapeutic tools for preventing and alleviating lipid accumulation.

There is a growing need to develop new approaches to prevent and treat diseases related to metabolic syndromes, including obesity or type 2 diabetes, that focus on the different factors involved in the pathogenesis of these diseases. Due to the role of gut microbiota in the regulation of glucose and insulin homeostasis, probiotics with beneficial properties have emerged as an alternative therapeutic tool to ameliorate metabolic diseases-related disturbances, including fat excess or inflammation. In the last few years, different strains of bacteria, mainly lactic acid bacteria (LAB) and species from the genus Bifidobacterium, have emerged as potential probiotics due to their anti-obesogenic and/or anti-diabetic properties. However, in vivo studies are needed to demonstrate the mechanisms involved in these probiotic features. In this context, Caenorhabditis elegans has emerged as a very powerful simple in vivo model to study the physiological and molecular effects of probiotics with potential applications regarding the different pathologies of metabolic syndrome. This review aims to summarize the main studies describing anti-obesogenic, anti-diabetic, or anti-inflammatory properties of probiotics using C. elegans as an in vivo research model, as well as providing a description of the molecular mechanisms involved in these activities.

Pediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate in EwS how cooperation of dominant oncogenes and regulatory germline variants determine tumor growth, patient survival and drug response. Binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancer-like DNA element controls expression of the transcription factor MYBL2 mediating these phenotypes. Whole-genome and RNA sequencing reveals that variability at this locus is inherited via the germline and is associated with variable inter-tumoral MYBL2 expression. High MYBL2 levels sensitize EwS cells for inhibition of its upstream activating kinase CDK2 in vitro and in vivo, suggesting MYBL2 as a putative biomarker for anti-CDK2-therapy. Collectively, we establish cooperation of somatic mutations and regulatory germline variants as a major determinant of tumor progression and highlight the importance of integrating the regulatory genome in precision medicine.

Many studies have shown the capacity of soil humic substances (HS) to improve plant growth in natural ecosystems. This effect involves the activation of different processes within the plant at different coordinated molecular, biochemical, and physiological levels. However, the first event triggered by plant root-HS interaction remains unclear. Some studies suggest the hypothesis that the interaction of HS with root exudates involves relevant modification of the molecular conformation of humic self-assembled aggregates, including disaggregation, which might be directly involved in the activation of root responses. To investigate this hypothesis, we have prepared two humic acids. A natural humic acid (HA) and a transformed humic acid obtained from the treatment of HA with fungal laccase (HA enz). We have tested the capacity of the two humic acids to affect plant growth (cucumber and Arabidopsis) and complex Cu. Laccase-treatment did not change the molecular size but increased hydrophobicity, molecular compactness and stability, and rigidity of HA enz. Laccase-treatment avoided the ability of HA to promote shoot- and root-growth in cucumber and Arabidopsis. However, it does not modify Cu complexation features. There is no molecular disaggregation upon the interaction of HA and HA enz with plant roots. The results indicate that the interaction with plant roots induced in both HA and laccase-treated HA (HA enz), changes in their structural features that showed higher compactness and rigidity. These events might result from the interaction of HA and HA enz with specific root exudates that can promote intermolecular crosslinking. In summary, the results indicate that the weakly bond stabilized aggregated conformation (supramolecular-like) of HA plays a crucial role in its ability to promote root and shoot growth. The results also indicate the presence of two main types of HS in the rhizosphere corresponding to those non-interacting with plant roots (forming aggregated molecular assemblies) and those produced after interacting with plant root exudates (forming stable macromolecules).

La colonoscopia es un procedimiento que generalmente se realiza con fines diagnósticos y terapéuticos, y su número ha aumentado exponencialmente en los últimos años. Es un procedimiento seguro con baja morbilidad, pero se deben conocer sus complicaciones. El diagnóstico de la apendicitis poscolonoscópica es difícil y las estrategias terapéuticas han variado a lo largo de los años. Este caso clínico muestra a un paciente que fue sometido a laparoscopia urgente por signos y síntomas de peritonitis local inducida por apendicitis aguda perforada 48 horas después de la colonoscopia.

Abstract Myxoid liposarcoma (MLS) represents a common subtype of liposarcoma molecularly characterized by a recurrent chromosomal translocation that generates a chimeric FUS-DDIT3 fusion gene. The FUS-DDIT3 oncoprotein has been shown to be crucial in MLS pathogenesis. Acting as a transcriptional dysregulator, FUS-DDIT3 stimulates proliferation and interferes with adipogenic differentiation. As the fusion protein represents a therapeutically challenging target, a profound understanding of MLS biology is elementary to uncover FUS-DDIT3-dependent molecular vulnerabilities. Recently, a specific reliance on the Hippo pathway effector and transcriptional co-regulator YAP1 was detected in MLS; however, details on the molecular mechanism of FUS-DDIT3-dependent YAP1 activation, and YAP1´s precise mode of action remain unclear. In elaborate in vitro studies, employing RNA interference-based approaches, small-molecule inhibitors, and stimulation experiments with IGF-II, we show that FUS-DDIT3-driven IGF-IR/PI3K/AKT signaling promotes stability and nuclear accumulation of YAP1 via deregulation of the Hippo pathway. Co-immunoprecipitation and proximity ligation assays revealed nuclear co-localization of FUS-DDIT3 and YAP1/TEAD in FUS-DDIT3-expressing mesenchymal stem cells and MLS cell lines. Transcriptome sequencing of MLS cells demonstrated that FUS-DDIT3 and YAP1 co-regulate oncogenic gene signatures related to proliferation, cell cycle progression, apoptosis, and adipogenesis. In adipogenic differentiation assays, we show that YAP1 critically contributes to FUS-DDIT3-mediated adipogenic differentiation arrest. Taken together, our study provides mechanistic insights into a complex FUS-DDIT3-driven network involving IGF-IR/PI3K/AKT signals acting on Hippo/YAP1, and uncovers substantial cooperative effects of YAP1 and FUS-DDIT3 in the pathogenesis of MLS.

In this study, the authors show that that oncogenic hijacking of PRC1 sensitizes genomically stable Ewing sarcoma cells for PLK1 inhibition alone or in synergy with a microtubule-destabilizing drug via induction of cytokinesis defects, rendering PRC1 a promising, broadly applicable predictive biomarker