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Pseudomonas aeruginosa (P. aeruginosa) poses a significant threat as a nosocomial pathogen due to its robust resistance mechanisms and virulence factors. This study integrates subtractive proteomics and ensemble docking to identify and characterize essential proteins in P. aeruginosa, aiming to discover therapeutic targets and repurpose commercial existing drugs. Using subtractive proteomics, we refined the dataset to discard redundant proteins and minimize potential cross-interactions with human proteins and the microbiome proteins. We identified 12 key proteins, including a histidine kinase and members of the RND efflux pump family, known for their roles in antibiotic resistance, virulence, and antigenicity. Predictive modeling of the three-dimensional structures of these RND proteins and subsequent molecular ensemble-docking simulations led to the identification of MK-3207, R-428, and Suramin as promising inhibitor candidates. These compounds demonstrated high binding affinities and effective inhibition across multiple metrics. Further refinement using non-covalent interaction index methods provided deeper insights into the electronic effects in protein-ligand interactions, with Suramin exhibiting superior binding energies, suggesting its broad-spectrum inhibitory potential. Our findings confirm the critical role of RND efflux pumps in antibiotic resistance and suggest that MK-3207, R-428, and Suramin could be effectively repurposed to target these proteins. This approach highlights the potential of drug repurposing as a viable strategy to combat P. aeruginosa infections.

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The breast microbiome presents a diverse microbial community that could affects health and disease states, in the context of breast cancer. Sequencing technologies have allowed describing the diversity and abundance of microbial communities among individuals. The complex tumoral microenvironment that includes the microbial composition could influence tumor growth. The imbalance of diversity and abundance inside the microbial community, known as dysbiosis plays a crucial role in this context. One the most prevalent bacterial genera described in breast invasive carcinoma are Bacillus, Pseudomonas, Brevibacillus, Mycobacterium, Thermoviga, Acinetobacter, Corynebacterium, Paenibacillus, Ensifer, and Bacteroides. Paenibacills genus shows a relation with patient survival. When the Paenibacills genus increases its abundance in patients with breast cancer, the survival probability decreases. Within this dysbiotic environment, various bacterial metabolites could play a pivotal role in the progression and modulation of breast cancer. Key bacterial metabolites, such as cadaverine, lipopolysaccharides (LPS), and trimethylamine N-oxide (TMAO), have been found to exhibit potential interactions within breast tissue microenvironments. Understanding the intricate relationships between dysbiosis and these metabolites in breast cancer may open new avenues for diagnostic biomarkers and therapeutic targets. Further research is essential to unravel the specific roles and mechanisms of these microbial metabolites in breast cancer progression.

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Histone methyltransferases (HMTs) comprise a subclass of epigenetic regulators. Dysregulation of these enzymes results in aberrant epigenetic regulation, commonly observed in various tumor types, including hepatocellular adenocarcinoma (HCC). Probably, these epigenetic changes could lead to tumorigenesis processes. To predict how histone methyltransferase genes and their genetic alterations (somatic mutations, somatic copy number alterations, and gene expression changes) are involved in hepatocellular adenocarcinoma processes, we performed an integrated computational analysis of genetic alterations in 50 HMT genes present in hepatocellular adenocarcinoma. Biological data were obtained through the public repository with 360 samples from patients with hepatocellular carcinoma. Through these biological data, we identified 10 HMT genes (SETDB1, ASH1L, SMYD2, SMYD3, EHMT2, SETD3, PRDM14, PRDM16, KMT2C, and NSD3) with a significant genetic alteration rate (14%) within 360 samples. Of these 10 HMT genes, KMT2C and ASH1L have the highest mutation rate in HCC samples, 5.6% and 2.8%, respectively. Regarding somatic copy number alteration, ASH1L and SETDB1 are amplified in several samples, while SETD3, PRDM14, and NSD3 showed a high rate of large deletion. Finally, SETDB1, SETD3, PRDM14, and NSD3 could play an important role in the progression of hepatocellular adenocarcinoma since alterations in these genes lead to a decrease in patient survival, unlike patients who present these genes without genetic alterations. Our computational analysis provides new insights that help to understand how HMTs are associated with hepatocellular carcinoma, as well as provide a basis for future experimental investigations using HMTs as genetic targets against hepatocellular carcinoma.

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For the first time we report the validation of reference genes in plants from a population of blueberry (Vaccinium corymbosum) clones cultured in vitro on a colchicine-supplemented medium. Nodal segment explants of the cultivar Duke were regenerated by organogenesis under different periods of colchicine 1 mg/L exposure (1, 2, 3, 5, 30 days). The clones selected for the study showed variability for phenotypic traits after 2 years of adaptation to field conditions, compared to plants of the donor genotype that were regenerated on a medium without colchicine. Vaccinium myrtillus (GAPDH) and Vaccinium macrocarpon (ATP1, NADH, RPOB and COX2) were used as reference genomes for primer design. The results show that colchicine treatments can cause genomic changes in blueberry plants. At the molecular level, exposure of plants to colchicine in early periods could promote an increase in gene expression of specific genes such as ATP1, COX2, GAPDH, MATK, NADH and RPOB. However, prolonged exposure (30 days) could decrease gene expression of the genes studied. For qPCR assays, the primers designed for ATP1, COX2, GAPDH and MATK genes showed high efficiency. In addition, the GAPDH, ATP1, NADH and COX2 genes showed high stability and could be recommended as potential reference genes for gene expression assays in Vaccinium.

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The biodegradation of rubber materials is considered as a sustainable recycling alternative, highlighting the use of microorganisms and enzymes in oxidative processes of natural rubber. Currently, the main challenge is the treatment of rubber materials such as waste tyres, where the mixture of rubber polymers with different additives and the cross-linked structure obtained due to the vulcanisation process positions them as highly persistent materials. This study characterises the degradation of different rubber-containing substrates in in vivo and in vitro processes using the bacterium Rhodococcus rhodochrous and the oxygenase latex clearing protein (Lcp) from the same strain. For the first time, the degradation of polyisoprene particles in liquid cultures of R. rhodochrous was analysed, obtaining up to 19.32% mass loss of the polymer when using it as the only carbon source. Scanning electron microscopy analysis demonstrated surface alteration of pure polyisoprene and vulcanised rubber particles after 2 weeks of incubation. The enzyme LcpRR was produced in bioreactors under rhamnose induction and its activity characterised in oxygen consumption assays at different enzyme concentrations. A maximum consumption of 28.38 µmolO2/min was obtained by adding 100 µg/mL LcpRR to a 2% (v/v) latex emulsion as substrate. The bioconversion of natural rubber into reaction degradation products or oligoisoprenoids was calculated to be 32.54%. Furthermore, the mass distribution of the oligoisoprenoids was analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and 17 degradation products, ranging from C20 to C100 oligoisoprenoids, were identified. The multi-enzymatic degradation capacity of R. rhodochrous positions it as a model microorganism in complex degradation processes such as in the case of tyre waste.

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Hashimoto thyroiditis (HT) is a pathology that often causes a gradual thyroid insufficiency in affected patients due to the autoimmune destruction of this gland. The cellular immune response mediated by T helper lymphocytes TH1 and TH17 can induce the HT disease. In this pathologic condition, there is an imbalance between the TH17 and Treg lymphocytes as well as a gut microbiota dysfunction. The objective of this work was to describe the interactions of the cell subpopulations that participate in HT. To achieve this goal, we generated a mathematical model that allowed the simulation of different scenarios for the dynamic interaction between thyroid cells, the immune system, and the gut microbiota. We used a hypothetical-deductive design of mathematical modeling based on a system of ordinary differential equations, where the state variables are the TH1, TH17, and Treg lymphocytes, the thyrocytes, and the bacteria from gut microbiota. This work generated a compartmental model of the cellular immune response occurring in the thyroid gland. It was observed that TH1 and TH17 lymphocytes could increase the immune cells' activity, as well as activate effector cells directly and trigger the apoptosis and inflammation processes of healthy thyrocytes indirectly. Likewise, the model showed that a reduction in Treg lymphocytes could increase the activity of TH17 lymphocytes when an imbalance of the gut microbiota composition occurred. The numerical results highlight the TH1, TH17, and bacterial balance of the gut microbiota activities as important factors for the development of HT disease.

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Gastric cancer (GC) is one of the most frequent tumors in the world. Stomach adenocarcinoma is a heterogeneous tumor, turning the prognosis prediction and patients' clinical management difficult. Some diagnosis tests for GC are been development using knowledge based in polymorphisms, somatic copy number alteration (SCNA) and aberrant histone methylation. This last event, a posttranslational modification that occurs at the chromatin level, is an important epigenetic alteration seen in several tumors including stomach adenocarcinoma. Histone methyltransferases (HMT) are the proteins responsible for the methylation in specific amino acids residues of histones tails. Here, were presented several HMTs that could be relating to GC process. We use public data from 440 patients with stomach adenocarcinoma. We evaluated the alterations as SCNAs, mutations, and genes expression level of HMTs in these aforementioned samples. As results, it was identified the 10 HMTs most altered (up to 30%) in stomach adenocarcinoma samples, which are the PRDM14, PRDM9, SUV39H2, NSD2, SMYD5, SETDB1, PRDM12, SUV39H1, NSD3, and EHMT2 genes. The PRDM9 gene is among most mutated and amplified HMTs within the data set studied. PRDM14 is downregulated in 79% of the samples and the SUV39H2 gene is down expressed in patients with recurred/progressed disease. Several HMTs are altered in many cancers. It is important to generate a genetic atlas of alterations of cancer-related genes to improve the understanding of tumorigenesis events and to propose novel tools of diagnosis and prognosis for the cancer control.

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Raspberry (Rubus sp.) is a berries fruit with an ongoing agricultural and commercial interest due to its high contents of flavonoids and nutrients beneficial for human health. The growing demand for raspberries is facing great challenges associated mainly with the dispersal of diseases, which produces a decrease in productivity and fruit quality. A broad range of genomic resources is available for other Rosaceae species; however, genomic resources for species of the Rubus genus are still limited. Here, we characterize the transcriptome of the Rubus idaeus (Var. Amira) in order to 1) provide clues in the transcriptional changes of R. idaeus against tomato ringspot virus (ToRSV); and 2) generate genomic resources for this economically important species. We generate more than 200 million sequencing reads from two mRNA samples of raspberry, infected and not infected by ToRSV, using Illumina technology. After de novo assembly, we obtained 68,853 predicted protein-coding sequences of which 71.3% and 61.3% were annotated using Gene Ontology and Pfam databases, respectively. Moreover, we find 2,340 genes with differential expression between raspberries infected and not infected by ToRSV. Analysis of these genes shows functional enrichments of the oxidation-reduction process, cell wall biogenesis, terpene synthase activity, and lyase activity. These genes could be involved in the raspberry immune response through the interaction of different metabolic pathways; however, this statement needs further investigations. Up-regulation of genes encoding terpene synthases, multicopper oxidases, laccases, and beta-glucosidases might suggest that these enzymes appear to be the predominant transcriptome immune response of R. idaeus against ToRSV. Furthermore, we identify thousands of molecular markers (i.e., SSRs and SNPs), increasing considerably the genomic resources currently available for raspberries. This study is the first report on investigating the transcriptional changes of R. idaeus against ToRSV.

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We report the case of a 42-year-old woman who was diagnosed with breast cancer that recurred 3 years later, with supraclavicular lymphadenopathy and dermal involvement. The main drug used in the therapy was trastuzumab; however, the association of this drug with docetaxel was not able to decrease or cease the effect of the inflammatory BCA component with erythema and thickening of the skin as well as the supraclavicular lymphadenopathy previously diagnosed. Thus, a combined therapy was required. The patient was started on 6 cycles (1 per month) of trastuzumab subcutaneous 600 mg, pertuzumab intravenous 840 mg (as an attack dose, later on 420 mg), and xeloda oral 1000 mg. As a result, the patient showed a significant improvement in erythema and thickening of the skin in the neck and the right part of her trunk, besides decrease in supraclavicular lymphadenopathy. After 6 cycles, her skin was almost restored. Intravenous trastuzumab can be an effective single agent; however, its association with other chemotherapies-such as pertuzumab-can present a synergic effect, which can increase the survival expectations of metastatic HER2+ patients. Additionally, as reported in the literature, the use of xeloda plays a key role in restoring the skin health of patients with breast cancer presenting with skin metastasis. Our findings suggest that trastuzumab, pertuzumab, and xeloda combined therapy, following the schedule and posology handled in this study, can be a good treatment for recurrent HER2+ breast cancer with signs of supraclavicular lymphadenopathy and severe inflammatory BCA component with erythema and thickening of the skin.

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Prognostic markers for cancer can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Gallbladder cancer (GBC) is a rare tumor that causes 165 087 deaths in the world annually. It is the most common cancer of the biliary tract and has a particularly high incidence in Chile, Japan, and northern India. Currently, there is no accurate diagnosis test or effective molecular markers for GBC identification. Several studies have focused on the discovery of genetic alterations in important genes associated with GBC to propose novel diagnosis pathways and to create prognostic profiles. To achieve this, we performed data-mining of GBC in public repositories, harboring 133 samples of GBC, allowing us to describe relevant somatic mutations in important genes and to propose a genetic alteration atlas for GBC. In our results, we reported the 14 most altered genes in GBC: arid1a, arid2, atm, ctnnb1, erbb2, erbb3, kmt2c, kmt2d, kras, pik3ca, smad4, tert, tp53, and znf521 in samples from Japan, the United States, Chile, and China. Missense mutations are common among these genes. The annotations of many mutations revealed their importance in cancer development. The observed annotations mentioned that several mutations found in this repository are probably oncogenic, with a putative loss-of-function. In addition, they are hotspot mutations and are probably linked to poor prognosis in other cancers. We identified another 11 genes, which presented a copy number alteration in gallbladder database samples, which are ccnd1, ccnd3, ccne1, cdk12, cdkn2a, cdkn2b, erbb2, erbb3, kras, mdm2, and myc. The findings reported here can help to detect GBC cancer through the development of systems based on genetic alterations, for example, the development of a mutation panel specifically for GBC diagnosis, as well as the creation of prognostic profiles to accomplish the development of GBC and its prevalence.