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Identifying novel breast cancer biomarkers will improve patient stratification, enhance therapeutic outcomes, and help develop non-invasive diagnostics. We compared the proteomic profiles of whole-cell and exosomal samples of representative breast cancer cell subtypes to evaluate the potential of extracellular vesicles as non-invasive disease biomarkers in liquid biopsies. Overall, differentially-expressed proteins in whole-cell and exosome samples (which included markers for invasion, metastasis, angiogenesis, and drug resistance) effectively discriminated subtypes; furthermore, our results confirmed that the proteomic profile of exosomes reflects breast cancer cell-of-origin, which underscores their potential as disease biomarkers. Our study will contribute to identifying biomarkers that support breast cancer patient stratification and developing novel therapeutic strategies. We include an open, interactive web tool to explore the data as a molecular resource that can explain the role of these protein signatures in breast cancer classification., (© 2024. The Author(s).)

The Western Sandpiper, Calidris mauri, is one of the most abundant migratory shorebirds in the Western Hemisphere. Both Bahia Santa Maria (SM) and Ensenada Pabellones (EP) in Sinaloa, Mexico, are critical wintering sites for this species. We described the presence and concentration of 16 organochlorine pesticides (OCPs) in Western Sandpiper muscle and liver tissues collected from SM and EP during the wintering (December-January) and premigration (March-April) periods of 2010 and 2011, respectively. The individual OCP concentrations varied from 0.003 to 0.127 μg/g dry weight (dw) and were lower than the established thresholds for either acute or chronic effects. Western Sandpipers in SM-Premigration had the highest frequency of OCPs (39.3%), followed by EP-Winter (32.1%) and SM-Winter (28.5%). The frequency of occurrence of all OCPs in the liver presented differences between sites during the wintering period as well as between the wintering and premigration periods in SM. As the primary organ responsible for pollutant detoxification, the liver may bioaccumulate these compounds. No clear trends were observed in muscle tissues or among age-sex groups. Our results showed evidence of OCP bioaccumulation in the Western Sandpiper during the wintering period, which may be related to hyperphagia during the premigration period and to the differential intake of OCP types and quantities between sites due to differences in their availability. However, these conclusions are based on relatively low sample sizes for some groups and require further study with non-pooled samples.

Introduction: Prostate cancer (PCa) is one of the most common malignancies in men worldwide. Serum prostate specific antigen (PSA) level has been extensively used as a biomarker to detect PCa. However, PSA is not cancer-specific and various non-malignant conditions, including benign prostatic hyperplasia (BPH), can cause a rise in PSA blood levels, thus leading to many false positive results., Objectives: In this study, we evaluated the potential of urinary metabolomic profiling for discriminating PCa from BPH., Methods: Urine samples from 64 PCa patients and 51 individuals diagnosed with BPH were analysed using 1 H nuclear magnetic resonance ( 1 H-NMR). Comparative analysis of urinary metabolomic profiles was carried out using multivariate and univariate statistical approaches., Results: The urine metabolomic profile of PCa patients is characterised by increased concentrations of branched-chain amino acids (BCAA), glutamate and pseudouridine, and decreased concentrations of glycine, dimethylglycine, fumarate and 4-imidazole-acetate compared with individuals diagnosed with BPH., Conclusion: PCa patients have a specific urinary metabolomic profile. The results of our study underscore the clinical potential of metabolomic profiling to uncover metabolic changes that could be useful to discriminate PCa from BPH in a clinical context.

The objectives of the study were to detect and genotype Cryptosporidium spp. and Giardia intestinalis in wastewater samples obtained from five cities with high transit of people in the State of São Paulo, Brazil, and at the entrance of a Wastewater Treatment Plant (WWTP) in Lima, Peru. Samples were collected and concentrated by centrifugation. The genomic DNA was extracted for molecular characterization by nested PCR for Cryptosporidium and double nested PCR for Giardia, followed by sequencing and phylogenetic analysis. G. intestinalis was found in 63.6 % of the samples, and the human assemblages A and B were identified. Cryptosporidium sp. was found in 36.4 % of the samples, and the species were corresponding to Cryptosporidium hominis, Cryptosporidium cuniculus, and Cryptosporidium muris. Results revealed the presence of human pathogenic Cryptosporidium species and G. intestinalis human pathogenic assemblages. Molecular tools highlight the importance to map the genetic diversity of these parasites, as well as to detect their epidemiological circulation pathway in the environment.

The study aims to identify the relevance of immunohistochemistry (IHC), copy number aberrations (CNA) and epigenetic disorders in BRCAness breast cancers (BCs). We studied 95 paraffin included BCs, of which 41 carried BRCA1/BRCA2 germline mutations and 54 were non hereditary (BRCAX/Sporadic). Samples were assessed for BRCA1ness and CNAs by Multiplex Ligation-dependent Probe Amplification (MLPA); promoter methylation (PM) was assessed by methylation-specific-MLPA and the expression of miR-4417, miR-423-3p, miR-590-5p and miR-187-3p by quantitative RT-PCR. IHC markers Ki67, ER, PR, HER2, CK5/6, EGFR and CK18 were detected with specific primary antibodies (DAKO, Denmark). BRCAness association with covariates was performed using multivariate binary logistic regression (stepwise backwards Wald option). BRCA1/2 mutational status (p = 0.027), large tumor size (p = 0.041) and advanced histological grade (p = 0.017) among clinic-pathological variables; ER (p < 0.001) among IHC markers; MYC (p < 0.001) among CNA; APC (p = 0.065), ATM (p = 0.014) and RASSF1 (p = 0.044) among PM; and miR-590-5p (p = 0.001), miR-4417 (p = 0.019) and miR-423 (p = 0.013) among microRNA expression, were the selected parameters significantly related with the BRCAness status. The logistic regression performed with all these parameters selected ER+ as linked with the lack of BRCAness (p = 0.001) and MYC CNA, APC PM and miR-590-5p expression with BRCAness (p = 0.014, 0.045 and 0.007, respectively). In conclusion, the parameters ER expression, APC PM, MYC CNA and miR-590-5p expression, allowed detection of most BRCAness BCs. The identification of BRCAness can help establish a personalized medicine addressed to predict the response to specific treatments.

Biomimetics of materials is based on adopting and reproducing a model in nature with a well-defined functionality optimized through evolution. An example is barrier polymers that protect living tissues from the environment. The protecting layer of fruits, leaves, and non-lignified stems is the plant cuticle. The cuticle is a complex system in which the cutin is the main component. Cutin is a biopolyester made of polyhydroxylated carboxylic acids of 16 and 18 carbon atoms. The biosynthesis of cutin in plants is not well understood yet, but a direct chemical route involving the self-assembly of either molecules or molecular aggregates has been proposed. In this work, we present a combined study using experimental and simulation techniques on self-assembled layers of monomers selectively functionalized with hydroxyl groups. Our results demonstrate that the number and position of the hydroxyl groups are critical for the interaction between single molecules and the further rearrangement. Also, the presence of lateral hydroxyl groups reinforces lateral interactions and favors the bi-dimensional growth (2D), while terminal hydroxyl groups facilitate the formation of a second layer caused by head-tail interactions. The balance of 2D/3D growth is fundamental for the plant to create a protecting layer both large enough in 2D and thick enough in 3D.

During the first 6 years of the Program of Genetic Counselling in Cancer of Valencia (eastern Spain), 310 mutations (155 in BRCA1 and 155 in BRCA2) in 1,763 hereditary breast (BC) and ovarian cancer (OC) families were identified. Of the mutations found 105 were distinct (53 in BRCA1 and 52 in BRCA2), eight new and 37 recurrent. Two of the novel mutations were frame-shift placed in exons 2 and 11 of BRCA1 and the remaining six were placed in BRCA2; four frame-shift (three in exon 11 and one in exon 23), one deletion of the entire exon 19 and one in the intervening sequence of exon 22. The BRCA1 mutations with higher recurrence were c.66&#95;68delAG, c.5123C > A, c.1961delA, c.3770&#95;3771delAG and c.5152+5G > A that covered 45.2% of mutations of this gene. The age of onset of BCs of c.68&#95;69delAG mutation carriers occurs later than for the other recurrent mutations of this gene (45 vs. 37 years; p = 0.008). The BRCA2 mutations with higher recurrence were c.9026&#95;9030delATCAT, c.3264insT and c.8978&#95;8991del14 which represented 43.2% of all mutations in this gene, being the most recurrent mutation by far c.9026&#95;9030delATCAT that represents 21.3% of BRCA2 mutations and 10.6% of all mutations. Probands with family histories of BC and OC, or OC and/or BC in at least two first degree relatives, were the more likely to have BRCA1/BRCA2 mutations (35.2% of the total mutations). And that most BRCA1mutations (73.19% mutations) occurred in probands with early-onset BC or with family history of OC.

Salmonella is a public and animal health problem due to the generation of strains multiresistant to antimicrobial products. The objective of this study was to determine prevalence and antimicrobial phenotypic and genotypic resistance of Salmonella spp. isolated from beef cattle carcasses killed in slaughterhouses of the north central zone of the State of Mexico. Sampling was carried out according to the European Directive 2001/471/EC; isolation and identification of the strain was carried out according to the Mexican Official Standard NOM-114-SSA1-1994; resistance was established by CMI according to the National Committees for Clinical Laboratory Standards (NCLS) and multiplex PCR according to Ahmed et al. (Journal of Applied Microbiology 106:402-409, 2009) with PSE-1, tetG, qnrS, FloR, STR, and sul1 oligonucleotides. Twenty-seven strains of Salmonella spp. were obtained from 327 samples (prevalence of 0.083); 19 strains (70 %) were resistant to 10 μg/ml of ampicillin, 15 of these (79 %) had the PSE-1 gene; 22 strains (84 %) were resistant to 30 μg/ml streptomycin, 14 of these (63.6 %) had the STR gene. Genes PSE-1 and STR were factors in the presence of resistance, the rest of the genes (tetG, qnrS, FloR, and sul1) were not factors of resistance in the studied strains.

Aim of the Study: Helophytes like rush and reed are increasingly used for phytoremediation of contaminated water. This study characterises the response of rush and reed plants to chemical stressors such as chlorobenzene, benzene and methyl-tert-butyl ether. The extractable wax layer of the cuticle was chosen for detailed investigations due to its multiple, particularly, protective functions for plants and its easy availability for analysis., Methods: The chemical composition of the cuticle wax layer of reed and rush was studied in dependence on chemical stress caused by contaminated water under wetland cultivation conditions. The lipid layer of leaves was extracted, derivatised and investigated by GC-MS using retention time locking and a plant-specific data base., Results: In case of rush, a remarkable increase of the total lipid layer and a prolongation of the mean chain length resulted as response on a chlorobenzene exposure. The significant difference in the substance profiles of exposed plants and controls could be confirmed by multivariate data analysis. The lipid layer of reed was not changed significantly when the plants were exposed to water polluted with benzene and methyl-tert-butyl ether. However, scanning electron microscopic images of the exposed reed leaves indicated alterations in the crystal structure of their wax surface., Conclusion: The composition and morphology of cuticular waxes indicated the plants' response to chemical stress very sensitively thus, changes in the wax layer could be used as an indication for growing in a contaminated area.

More than 20 infectious agents, ranging from retroviruses to mycobacteria, have been associated with multiple sclerosis onset or relapses in which oligodendrocytes, the myelin-forming cells of the central nervous system, are the initial target of the pathogenic status. In this work, the nature of the susceptibility of the human precursor oligodendroglial KG-1C cell line to herpes simplex virus type 1 (HSV-1) was investigated. Infection of KG-1C cells was characterized by a high level of virus production and a notable progression of the cytopathic effect. After infection, there was a significant shut-off of host mRNA translation, which was correlated with evident synthesis of viral proteins. An examination by electron microscopy of the infected cells revealed the presence of large clusters of mitochondria located in the proximity of intracellular HSV-1 particle groups. In addition, transmission electron microscopy and nuclear fluorescence analysis showed neither signs of chromatin condensation nor of apoptotic bodies. Furthermore, procaspase-3 remained uncleaved, suggesting that apoptosis does not take place, at least in this system. Finally, expression and localization of MAL2, a subpopulation of detergent-insoluble lipid raft protein, was studied. Detection of MAL2 significantly increased after infection and it was colocalized with HSV-1 proteins. From these findings the authors conclude that human oligodendrocyte-like cells are highly susceptible to HSV-1 infection. The implications of this for central nervous system viral infection are discussed.

We describe the effect of pretreatment with alpha-2-macroglobulin (A2M) on the susceptibility of the human neuroblastoma SKNMC cell line to infection by herpes virus type 1 (HSV-1). ELISA and co-immunoprecipitation experiments confirmed the A2M-HSV-1 interaction in vitro. Indirect immunofluorescence shows that A2M exacerbated the cytopathic effect induced after HSV-1 infection. However, A2M-pretreated SKNMC cells notably produced fewer HSV-1 particles than did the untreated cells, suggesting that A2M could induce a restrictive infection. Furthermore, high levels of HSV-1 and A2M induced the production of nitric oxide (NO) in SKNMC. Preliminary results suggest that A2M might induce apoptosis in HSV-1-infected cells. These findings affirm the conclusion that A2M may interact directly with HSV-1 and modulate the course of the infection in SKNMC human neuroblastoma cells.

In the University Hospital of Granada (Spain), 359 surgical trauma patients underwent intraoperative autotransfusion. The patients were divided into 2 groups, according to their blood loss: group I (blood loss less than or equal to 2000 ml) and group II (blood loss greater than 2000 ml). Patients from group I did not require homologous blood transfusion. So the high risk involved in this type of transfusion was avoided. Macroscopic haemoglobinuria was only found in those patients where the Solcotrans, Viavae type of autotransfusion system was used; with the Bentley ATS system, no macroscopic haemoglobinuria was registered. With patients from group II, however, that is, those with a blood loss of more than 2000 ml, we had to fall back on homologous transfusion in addition to retransfusing autologous blood. When the transfusion exceeds 4000 ml there is increasing bleeding, which requires treatment with fresh frozen plasma, platelets and/or fibrinogen. The mortality rate of patients in group II was very high but the patients died from the severity of their injuries or from postoperative complications which were not due to autotransfusion in itself with the exception of 3 patients who underwent massive autotransfusion (12,000 to 25,000 ml) and died from acute renal failure. The main indication for intraoperative autotransfusion is without doubt abdominal and thoracic trauma which lead to high blood loss.