The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role ...in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways' role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.
Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is ...understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.
The chemical and mineralogical composition of steel slag produced in two ArcelorMittal steel plants located in the North of Spain, as well as the study of the influence of simulated environmental ...conditions on the properties of the slag stored in disposal areas, was carried out by elemental chemical analysis, XRF, X-ray diffraction, thermal analysis, and scanning electron microscopy with EDS analyzer. Spectroscopic characterization of the slag was also performed by using FTIR spectroscopy. Due to the potential uses of the slag as low cost adsorbent for water treatment and pollutants removal, its detailed textural characterization was carried out by nitrogen adsorption−desorption at 77 K and mercury intrusion porosimetry. The results show that the slag is a crystalline heterogeneous material whose main components are iron oxides, calcium (magnesium) compounds (hydroxide, oxide, silicates, and carbonate), elemental iron, and quartz. The slags are porous materials with specific surface area of 11 m2g−1, containing both mesopores and macropores. Slag exposure to simulated environmental conditions lead to the formation of carbonate phases. Carbonation reduces the leaching of alkaline earth elements as well as the release of the harmful trace elements Cr (VI) and V. Steel slags with high contents of portlandite and calcium silicates are potential raw materials for CO2 long-term storage.
The constant changes in cancer cell bioenergetics are widely known as metabolic reprogramming. Reprogramming is a process mediated by multiple factors, including oncogenes, growth factors, ...hypoxia-induced factors, and the loss of suppressor gene function, which support malignant transformation and tumor development in addition to cell heterogeneity. Consequently, this hallmark promotes resistance to conventional anti-tumor therapies by adapting to the drastic changes in the nutrient microenvironment that these therapies entail. Therefore, it represents a revolutionary landscape during cancer progression that could be useful for developing new and improved therapeutic strategies targeting alterations in cancer cell metabolism, such as the deregulated mTOR and PI3K pathways. Understanding the complex interactions of the underlying mechanisms of metabolic reprogramming during cancer initiation and progression is an active study field. Recently, novel approaches are being used to effectively battle and eliminate malignant cells. These include biguanides, mTOR inhibitors, glutaminase inhibition, and ion channels as drug targets. This review aims to provide a general overview of metabolic reprogramming, summarise recent progress in this field, and emphasize its use as an effective therapeutic target against cancer.
Since the inception of the integrated model, educational leaders have predicted its ongoing evolution, as the optimal plastic surgery curriculum remains a source of debate. With the now complete ...elimination of the "coordinated" pathway, the total number of integrated programs has arguably reached a plateau. Accordingly, this study examines the current state of training in integrated residencies and reevaluates the variability in the first 3 years of training observed previously.
Program information was obtained for all 68 integrated plastic surgery programs, and rotation schedules were available for 59. Plastic, general, and subspecialty surgery exposures were quantified and compared. Inclusion of rotations "strongly suggested" by the Residency Review Committee was also examined.
Plastic surgery exposure ranged from 3.5 to 25 months (mean, 13.9 ± 5.4 months). General surgery ranged from 5 to 22.5 months (mean, 12.8 ± 4.7 months). Subspecialty rotations ranged from 0 to 8 months (mean, 3.6 ± 1.8 months). There was no difference in mean plastic surgery exposure between programs based within departments versus divisions (15.4 months versus 13.3 months; p = 0.184). There remained significant variability in the inclusion of 18 non-plastic surgery rotations, including the "strongly suggested" rotations.
Plastic surgery exposure remains highly variable with a greater than 7-fold difference between programs. This suggests that programs are still sorting out the ideal curriculum. However, there is an overall trend toward earlier and increased plastic surgery exposure, which now exceeds the average time spent on general surgery rotations.
Mapping-by-sequencing combines Next Generation Sequencing (NGS) with classical genetic mapping by linkage analysis to establish gene-to-phenotype relationships. Although numerous tools have been ...developed to analyze NGS datasets, only a few are available for mapping-by-sequencing. One such tool is Easymap, a versatile, easy-to-use package that performs automated mapping of point mutations and large DNA insertions. Here, we describe Easymap v.2, which also maps small insertion/deletions (InDels), and includes workflows to perform QTL-seq and variant density mapping analyses. Each mapping workflow can accommodate different experimental designs, including outcrossing and backcrossing, F
, M
, and M
mapping populations, chemically induced mutation and natural variant mapping, input files containing single-end or paired-end reads of genomic or complementary DNA sequences, and alternative control sample files in FASTQ and VCF formats. Easymap v.2 can also be used as a variant analyzer in the absence of a mapping algorithm and includes a multi-threading option.
Naratriptan, active pharmaceutical ingredient with antimigraine activity was electrochemically detected in untreated screen-printed carbon electrodes (SPCEs). Cyclic voltammetry and differential ...pulse voltammetry were used to carry out quantitative analysis of this molecule (in a Britton-Robinson buffer solution at pH 3.0) through its irreversible oxidation (diffusion controlled) at a potential of +0.75V (vs. Ag pseudoreference electrode). Naratriptan oxidation product is an indole based dimer with a yellowish colour (maximum absorption at 320nm) so UV–VIS spectroelectrochemistry technique was used for the very first time as an in situ characterization and quantification technique for this molecule. A reflection configuration approach allowed its measurement over the untreated carbon based electrode. Finally, time resolved Raman Spectroelectrochemistry is used as a powerful technique to carry out qualitative and quantitative analysis of Naratriptan. Electrochemically treated silver screen-printed electrodes are shown as easy to use and cost-effective SERS substrates for the analysis of Naratriptan.
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•Detection of Naratriptan was carried out using screen-printed electrodes.•UV/VIS spectroelectrochemistry was used to detect Naratriptan oxidation product.•In situ SERS effect of Naratriptan in silver screen-printed electrodes is reported.•Low µM detection was achieved by electrochemical and SERS methods.
Most members of the large family of ATP-Binding Cassette (ABC) proteins function as membrane transporters. However, the most evolutionarily conserved group, the ABCE protein subfamily, comprises ...soluble proteins that were initially denoted RNase L inhibitor (RLI) proteins. ABCE proteins are present in all eukaryotes and archaea and are encoded by a single gene in most genomes, or by two genes in a few cases. Functional analysis of
genes, primarily in
, has shown that ABCE proteins have essential functions as part of the translational apparatus. In this review, we summarize the current understanding of ABCE protein function in ribosome biogenesis and recycling, with a particular focus on their known and proposed developmental roles in different species. The ABCE proteins might represent another class of factors contributing to the role of the ribosome in gene expression regulation.
To evaluate the effectiveness of opioid maintenance programs in treating opioid dependence in Spanish prisons.
A narrative bibliographic review was carried out on the following databases: PubMed; ...Cochrane; IBECS; LILACS; HealthCare. All clinical trials were chosen as a preference, along with systematic review articles and some articles that were considered relevant for their content. The time period was limited to between January 2011 and November 2021. The languages chosen were English, Spanish and Catalan. Repeated articles and those that were not related to the objectives were rejected. The search criteria were: "methadone AND prisons"; "opiate substitution treatment AND prisons"; "methadone AND buprenorphine"; "methadone OR buprenorphine"; "prisons AND Methadone AND buprenorphine".
20 articles were selected out of 647 items consulted after applying the corresponding filters and after discarding duplicates.
There was a slightly greater effectiveness of buprenorphine versus methadone. The high prevalence of the program was highlighted, as well as the variety of adverse effects of methadone. Usefulness with regard to inmates' behavior showed a range of opinions. The possibility of new treatment alternatives with better pharmacological control is mentioned.
Longevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon ...characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.
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