Antinociceptive and Anti-Inflammatory Effects of Total Alkaloid Extract from Fumaria capreolata

Fumaria capreolata is used in traditional medicine in North Africa for its gastrointestinal and anti-inflammatory activities. The present study investigates the effects of total alkaloids extracted from the aerial parts of Fumaria capreolata (AFC) on LPS-induced production of proinflammatory mediators (IL-6, IL-1β, iNOS, TNF-α, COX-2, and MIP-2) in RAW264.7 cells. AFC significantly reduced the inflammatory response inhibiting the production of nitric oxide (NO) and IL-6 in a dose-dependent manner, without affecting the viability of cells, and downregulated mRNA expression of proinflammatory key players: IL-6, IL-1β, iNOS, TNF-α, and COX-2. AFC antinociceptive and anti-inflammatory properties were also evaluated on the acetic acid- and formalin-induced pain models in mice. AFC oral administration significantly inhibited acetic acid-induced writhes and reduced formalin-induced paw licking time. Therefore, AFC may be a potential candidate for the treatment of inflammatory diseases, such as colitis and arthritis

Cellular and Molecular Mechanisms of Methotrexate Resistance in Melanoma

Endocrinolog

Flavonoids in Inflammatory Bowel Disease: A Review

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects.This work was supported by Junta de Andalucia (P10-AGR-6826 and CTS 164) and by the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union.The CIBER-EHD is funded by the Instituto de Salud Carlos III

The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition

Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.This work was supported by Junta de Andalucía (Spain) (research grants CTS 164 and PI-0206-2016) and cofinanced by the Fondo Europeo de Desarollo Regional (FEDER) from the European Union. RM has a Río Hortega contract (CM17/00237) and PA has a Nicolás Monardes contract (C-0013-2018)

Plan de responsabilidad social empresarial grupo empresarial Activos S.A.S.

Plan de responsabilidad social empresarial grupo empresarial Activos S.A.S.En el presente escrito se consolida la elaboración del plan de responsabilidad social empresarial del grupo empresarial Activos S.A.S, compañía dedicada a la prestación de servicios temporales que específicamente realiza la administración de recurso humano de sus clientes. El respectivo plan de RSE está desarrollado a partir de diferentes fases, inicialmente se realizó una evaluación de desempeño de la empresa, donde se define la necesidad de realizar un programa de RSE, bajo una serie de estrategias que impacten al grupo empresarial Activos S.A.S., la segunda fase consolida código de conducta empresarial, donde se genera las políticas y responsabilidades que cada actor de la organización debe tener en cuenta para articularse dentro del plan estratégico de la empresa, se tuvo como guía en esta fase las iniciativas mundiales para su elaboración. En la tercera fase se realiza el mapa de Stakeholders y la matriz de influencia, definiendo los diferentes grupos de interés y su nivel de impacto, de ahí, se elabora el plan RSE, bajo los objetivos, estrategias y sus respectivos indicadores, los cuales relacionan el resultado esperado durante su implementación, permitiendo así verificar si las actividades propuestas cumplen con los resultados esperados y de esta manera enfocar a la organización desde su contribución activa y voluntaria a una mejor sociedad colombiana.This text consolidates the development of the Corporate Social Responsibility plan of the Activos S.A.S. business group, a company dedicated to the provision of temporary services that specifically performs the administration of human resources of its customers. The respective CSR plan is developed from different phases, initially a performance evaluation of the company was carried out, which defines the need to carry out a program of CSR, under a series of strategies that impact the Activos S.A.S. business group, the second phase consolidates the code of business conduct, where the policies and responsibilities that each actor of the organization must take into account to articulate within the companys strategic plan, the global initiatives for the development of global. In the third phase the stakeholder map and the influence matrix are carried out, defining the different stakeholders and their level of impact, hence the CSR plan is developed, under the objectives, strategies and their respective indicators, which relate the expected result during its implementation, this allowing to verify whether the proposed activities meet the expected results and thus focus the organization from its active and voluntary contribution to a better Colombian society

Intestinal anti-inflammatory effects of goat whey on DNBS-induced colitis in mice

This study evaluated the intestinal anti-inflammatory effects of goat whey in a mouse model of colitis induced by 2,4-dinitrobenzenesulfonic acid that resembles human IBD. At a concentration of 4 g/kg/day, the goat whey improved the symptoms of intestinal inflammation, namely by decreasing the disease activity index, colonic weight/length, and leukocyte infiltration. Moreover, goat whey inhibited NF-kappa B p65 and p38 MAPK signaling pathways and consequently down-regulated the gene expression of various proinflammatory markers such as IL-1 beta, IL-6, IL-17, TNF-alpha, iNOS, MMP-9, ICAM-1. Also, goat whey increased the expression of proteins such as mucins, occludin proteins and cytokine signalling suppressors. The immunomodulatory properties of goat whey were also evaluated in vitro using the murine macrophage cell line Raw 264 and CMT-93 cells derived from mouse rectum carcinomas. The results revealed the ability of goat whey to inhibit the production of NO and reduce IL-6 production in LPS-stimulated cells. In conclusion, goat whey exhibited antiinflammatory effects in the DNBS model of intestinal inflammation, and these observations were confirmed by its immunomodulatory properties in vitro. Together, our results indicate that goat whey could have applications for the treatment of IBD.info:eu-repo/semantics/publishedVersio

Gene Editing in Adult Hematopoietic Stem Cells

Over the last years, an important development has allowed the scientific community to address a precise and accurate modification of the genome. The first probe of concept appeared with the design and use of engineered zinc-finger nucleases (ZFNs), which was expanded later on with the discovery and engineering of meganucleases and transcription activator-like effector nucleases (TALENs) and finally democratized and made easily available to the whole scientific community with the discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease combination technology. The availability of these tools has allowed a precise gene editing, such as knockout of a specific gene or the correction of a defective gene by means of homologous recombination (HR), taking advantage of the endogenous cell repair machinery. This process was already known and used but was inefficient—efficiency that has been increased more than 100-fold with the addition of the mentioned specific nucleases to the process. Apart from the proper design of the nucleases to recognize and cut the selected site in the cell genome, two main goals need to be adequately addressed to optimize its function: the delivery of the tools into the desired cells and the selection of those where the gene editing process has occurred correctly. Both steps can be easily solved when the source of cells is extensive or can be expanded and manipulated in vitro extensively, such as immortalized cell lines or pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells). However, both steps are critical in the case of primary cells, such as the hematopoietic stem cells (HSCs). HSCs are a rare cell population present in the bone marrow (BM) of higher mammals, and it is the responsible for the maintenance and replenishment of all hematopoietic cells for the lifespan of the animals by means of two fundamental properties: self-renewal and multipotency. HSC population is then the ideal target for the correction of hematopoietic genetic diseases and also for the knockout of the responsible genes to in vitro and in vivo model those hematopoietic diseases. This rare population cannot be expanded and its in vitro manipulation and culture negatively affects their fundamental properties of self-renewal and multipotency. These factors challenge the application of gene editing to HSCs. Important efforts are now ongoing trying to optimize the protocols of gene delivery and selection for HSCs. This chapter will review and discuss how researchers are trying to solve them, all attempts that are ongoing and the potential application of the technology to the patients affected with hematopoietic genetic diseases

How Frequently Benign Uterine Myomas Appear Suspicious for Sarcoma as Assessed by Transvaginal Ultrasound?

Uterine myomas may resemble uterine sarcomas in some cases. However, the rate of benign myomas appearing as sarcomas at an ultrasound examination is not known. The objective of this study is to determine the percentage of benign myomas that appear suspicious for uterine sarcoma on ultrasound examination. This is a prospective observational multicenter study (June 2019-December 2021) comprising a consecutive series of patients with histologically proven uterine myoma after hysterectomy or myomectomy who underwent transvaginal and/or transabdominal ultrasound prior to surgery. All ultrasound examinations were performed by expert examiners. MUSA criteria were used to describe the lesions (1). Suspicion of sarcoma was established when three or more sonographic features, described by Ludovisi et al. as "frequently seen in uterine sarcoma", were present (2). These features are no visible myometrium, irregular cystic areas, non-uniform echogenicity, irregular contour, "cooked" appearance, and a Doppler color score of 3-4. In addition, the examiners had to classify the lesion as suspicious based on her/his impression, independent of the number of features present. Eight hundred and ten women were included. The median maximum diameter of the myomas was 58.7 mm (range: 10.0-263.0 mm). Three hundred and forty-nine (43.1%) of the patients had more than one myoma. Using the criterion of >3 suspicious features, 40 (4.9%) of the myomas had suspicious appearance. By subjective impression, the examiners considered 40 (4.9%) cases suspicious. The cases were not exactly the same. We conclude that approximately 5% of benign uterine myomas may exhibit sonographic suspicion of sarcoma. Although it is a small percentage, it is not negligible

Low prevalence of methicillin-resistant Staphylococcus aureus nasal carriage in urban and rural community settings in Bolivia and Peru☆

Summary Objective To investigate the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage in rural and urban community settings of Bolivia and Peru. Methods MRSA nasal carriage was investigated in 585 individuals living in rural and urban areas of Bolivia and Peru (one urban area, one small rural village, and two native communities, one of which was highly isolated). MRSA isolates were subjected to molecular analysis for the detection of virulence genes, characterization of the staphylococcal cassette chromosome mec (SCC mec ), and genotyping (multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE)). Results An overall very low prevalence of MRSA nasal carriage was observed (0.5%), with MRSA carriers being detected only in a small rural village of the Bolivian Chaco. The three MRSA isolates showed the characteristics of community-associated MRSA (being susceptible to all non-beta-lactam antibiotics and harboring the SCC mec type IV), were clonally related, and belonged to ST1649. Conclusions This study provides an insight into the epidemiology of MRSA in community settings of Bolivia and Peru. Reliable, time-saving, and low-cost methods should be implemented to encourage continued surveillance of MRSA dissemination in resource-limited countries