The Clinical Utility of lncRNAs and Their Application as Molecular Biomarkers in Breast Cancer.

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, and treatment response. Particularly, the lncRNAs DSCAM-AS1 and GATA3-AS1 serve as examples of this because of their high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates to use as molecular biomarkers in clinical practice. However, lncRNA studies in breast cancer are limited in sample size and are restricted to the determination of their biological function, which represents an obstacle for its inclusion as molecular biomarkers of clinical utility. Nevertheless, due to their expression specificity among diseases, such as cancer, and their stability in body fluids, lncRNAs are promising molecular biomarkers that could improve the reliability, sensitivity, and specificity of molecular techniques used in clinical diagnosis. The development of lncRNA-based diagnostics and lncRNA-based therapeutics will be useful in routine medical practice to improve patient clinical management and quality of life.

Identification by molecular techniques of halophilic bacteria producing important enzymes from pristine area in Campeche, Mexico / Identificação por técnicas moleculares de bactérias halofílicas que produzem enzimas importantes em área intocada de Campeche, México

Isla Arena is located in the coordinate 20° 70´ N - 90° 45´ W, from Campeche, Mexico. In these estuaries, the ocean mixes with fresh water, and ecosystems are concentrated where petenes and pink flamingos proliferate. Crustaceans and mollusks abound in the sea. Despite its enormous marine wealth, there are no studies carried out on which halophilic microorganisms are present in these waters. In this work, the diversity and structure of the microbial community was investigated through a metagenomics approach and corroborated for sequencing of 16S rRNA genes. It was found that the phylum Fimicutes predominates with more than 50%, in almost the same proportion of the class Bacilli and with almost 41% of relative abundance of the order Bacillales. The sequencing results showed that one of the samples presented a high percentage of similarity (99.75%) using the Nucleotide BLAST program with a peculiar microorganism: Bacillus subtilis. This microorganism is one of the best characterized bacteria among the gram-positive ones. Our results demonstrate that B. subtilis can be an efficient source of proteases, lipases and cellulases, from halophilic microbial communities located in poorly explored areas.

Isla Arena está localizada na coordenada 20°70’N - 90°45’W, de Campeche, México. Nesses estuários, o oceano se mistura com a água doce e os ecossistemas se concentram onde proliferam petenos e flamingos rosa. Crustáceos e moluscos abundam no mar. Apesar de sua enorme riqueza marinha, não há estudos realizados sobre a presença de microrganismos halofílicos nessas águas. Neste trabalho, a diversidade e estrutura da comunidade microbiana foram investigadas através de uma abordagem metagenômica e corroboradas para o sequenciamento de genes 16S rRNA. Verificou-se que o filo Fimicutes predomina com mais de 50%, quase na mesma proporção da classe Bacilli e com quase 41% de abundância relativa da ordem Bacillales. Os resultados do sequenciamento mostraram que uma das amostras apresentou alto percentual de similaridade (99,75%) pelo programa Nucleotide BLAST com um microrganismo peculiar: Bacillus subtilis. Nossos resultados demonstram que B. subtilis pode ser uma fonte eficiente de proteases, lipases e celulases, provenientes de comunidades microbianas halofílicas localizadas em áreas pouco exploradas.

Identification by molecular techniques of halophilic bacteria producing important enzymes from pristine area in Campeche, Mexico

Abstract Isla Arena is located in the coordinate 20° 70´ N - 90° 45´ W, from Campeche, Mexico. In these estuaries, the ocean mixes with fresh water, and ecosystems are concentrated where petenes and pink flamingos proliferate. Crustaceans and mollusks abound in the sea. Despite its enormous marine wealth, there are no studies carried out on which halophilic microorganisms are present in these waters. In this work, the diversity and structure of the microbial community was investigated through a metagenomics approach and corroborated for sequencing of 16S rRNA genes. It was found that the phylum Fimicutes predominates with more than 50%, in almost the same proportion of the class Bacilli and with almost 41% of relative abundance of the order Bacillales. The sequencing results showed that one of the samples presented a high percentage of similarity (99.75%) using the Nucleotide BLAST program with a peculiar microorganism: Bacillus subtilis. This microorganism is one of the best characterized bacteria among the gram-positive ones. Our results demonstrate that B. subtilis can be an efficient source of proteases, lipases and cellulases, from halophilic microbial communities located in poorly explored areas.

Resumo Isla Arena está localizada na coordenada 20°70N - 90°45W, de Campeche, México. Nesses estuários, o oceano se mistura com a água doce e os ecossistemas se concentram onde proliferam petenos e flamingos rosa. Crustáceos e moluscos abundam no mar. Apesar de sua enorme riqueza marinha, não há estudos realizados sobre a presença de microrganismos halofílicos nessas águas. Neste trabalho, a diversidade e estrutura da comunidade microbiana foram investigadas através de uma abordagem metagenômica e corroboradas para o sequenciamento de genes 16S rRNA. Verificou-se que o filo Fimicutes predomina com mais de 50%, quase na mesma proporção da classe Bacilli e com quase 41% de abundância relativa da ordem Bacillales. Os resultados do sequenciamento mostraram que uma das amostras apresentou alto percentual de similaridade (99,75%) pelo programa Nucleotide BLAST com um microrganismo peculiar: Bacillus subtilis. Nossos resultados demonstram que B. subtilis pode ser uma fonte eficiente de proteases, lipases e celulases, provenientes de comunidades microbianas halofílicas localizadas em áreas pouco exploradas.

Identification by molecular techniques of halophilic bacteria producing important enzymes from pristine area in Campeche, Mexico / Identificação por técnicas moleculares de bactérias halofílicas que produzem enzimas importantes em área intocada de Campeche, México

Abstract Isla Arena is located in the coordinate 20° 70´ N - 90° 45´ W, from Campeche, Mexico. In these estuaries, the ocean mixes with fresh water, and ecosystems are concentrated where petenes and pink flamingos proliferate. Crustaceans and mollusks abound in the sea. Despite its enormous marine wealth, there are no studies carried out on which halophilic microorganisms are present in these waters. In this work, the diversity and structure of the microbial community was investigated through a metagenomics approach and corroborated for sequencing of 16S rRNA genes. It was found that the phylum Fimicutes predominates with more than 50%, in almost the same proportion of the class Bacilli and with almost 41% of relative abundance of the order Bacillales. The sequencing results showed that one of the samples presented a high percentage of similarity (99.75%) using the Nucleotide BLAST program with a peculiar microorganism: Bacillus subtilis. This microorganism is one of the best characterized bacteria among the gram-positive ones. Our results demonstrate that B. subtilis can be an efficient source of proteases, lipases and cellulases, from halophilic microbial communities located in poorly explored areas.

Resumo Isla Arena está localizada na coordenada 20°70'N - 90°45'W, de Campeche, México. Nesses estuários, o oceano se mistura com a água doce e os ecossistemas se concentram onde proliferam petenos e flamingos rosa. Crustáceos e moluscos abundam no mar. Apesar de sua enorme riqueza marinha, não há estudos realizados sobre a presença de microrganismos halofílicos nessas águas. Neste trabalho, a diversidade e estrutura da comunidade microbiana foram investigadas através de uma abordagem metagenômica e corroboradas para o sequenciamento de genes 16S rRNA. Verificou-se que o filo Fimicutes predomina com mais de 50%, quase na mesma proporção da classe Bacilli e com quase 41% de abundância relativa da ordem Bacillales. Os resultados do sequenciamento mostraram que uma das amostras apresentou alto percentual de similaridade (99,75%) pelo programa Nucleotide BLAST com um microrganismo peculiar: Bacillus subtilis. Nossos resultados demonstram que B. subtilis pode ser uma fonte eficiente de proteases, lipases e celulases, provenientes de comunidades microbianas halofílicas localizadas em áreas pouco exploradas.

Influence of nitric oxide signaling mechanisms in cancer.

Nitric oxide (NO) is a molecule with multiple biological functions that is involved in various pathophysiological processes such as neurotransmission and blood vessel relaxation as well as the endocrine system, immune system, growth factors, and cancer. However, in the carcinogenesis process, it has a dual behavior; at low doses, NO regulates homeostatic functions, while at high concentrations, it promotes tissue damage or acts as an agent for immune defense against microorganisms. Thus, its participation in the carcinogenic process is controversial. Cancer is a multifactorial disease that presents complex behavior. A better understanding of the molecular mechanisms associated with the initiation, promotion, and progression of neoplastic processes is required. Some hypotheses have been proposed regarding the influence of NO in activating oncogenic pathways that trigger carcinogenic processes, because NO might regulate some signaling pathways thought to promote cancer development and more aggressive tumor growth. Additionally, NO inhibits apoptosis of tumor cells, together with the deregulation of proteins that are involved in tissue homeostasis, promoting spreading to other organs and initiating metastatic processes. This paper describes the signaling pathways that are associated with cancer, and how the concentration of NO can serve a beneficial or pathological function in the initiation and promotion of neoplastic events.

Identification by molecular techniques of halophilic bacteria producing important enzymes from pristine area in Campeche, Mexico.

Isla Arena is located in the coordinate 20° 70´ N - 90° 45´ W, from Campeche, Mexico. In these estuaries, the ocean mixes with fresh water, and ecosystems are concentrated where petenes and pink flamingos proliferate. Crustaceans and mollusks abound in the sea. Despite its enormous marine wealth, there are no studies carried out on which halophilic microorganisms are present in these waters. In this work, the diversity and structure of the microbial community was investigated through a metagenomics approach and corroborated for sequencing of 16S rRNA genes. It was found that the phylum Fimicutes predominates with more than 50%, in almost the same proportion of the class Bacilli and with almost 41% of relative abundance of the order Bacillales. The sequencing results showed that one of the samples presented a high percentage of similarity (99.75%) using the Nucleotide BLAST program with a peculiar microorganism: Bacillus subtilis. This microorganism is one of the best characterized bacteria among the gram-positive ones. Our results demonstrate that B. subtilis can be an efficient source of proteases, lipases and cellulases, from halophilic microbial communities located in poorly explored areas.

Transcriptional Profiles Reveal Deregulation of Lipid Metabolism and Inflammatory Pathways in Neurons Exposed to Palmitic Acid.

The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to it have not been largely investigated. Given that PA affects a variety of metabolic pathways, we aimed to analyze the transcriptomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome pathway analysis revealed a pattern of gene expression which is associated with inflammatory pathways, and importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by quantitative RT-PCR (qRT-PCR) of Hmgcs2, Angptl4, Ugt8, and Rnf145 support the results obtained by RNAseq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases.

Morphological and Mechanical Properties of Electrospun Polycaprolactone Scaffolds: Effect of Applied Voltage.

The aim of this work is to investigate the effect of the applied voltage on the morphological and mechanical properties of electrospun polycaprolactone (PCL) scaffolds for potential use in tissue engineering. The morphology of the scaffolds was characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), and the BET techniques for measuring the surface area and pore volume. Stress-strain curves from tensile tests were obtained for estimating the mechanical properties. Additional studies for detecting changes in the chemical structure of the electrospun PCL scaffolds by Fourier transform infrared were performed, while contact angle and X-ray diffraction analysis were realized for determining the wettability and crystallinity, respectively. The SEM, AFM and BET results demonstrate that the electrospun PCL fibers exhibit morphological changes with the applied voltage. By increasing the applied voltage (10 to 25 kV) a significate influence was observed on the fiber diameter, surface roughness, and pore volume. In addition, tensile strength, elongation, and elastic modulus increase with the applied voltage, the crystalline structure of the fibers remains constant, and the surface area and wetting of the scaffolds diminish. The morphological and mechanical properties show a clear correlation with the applied voltage and can be of great relevance for tissue engineering.

A potential inflammatory role of IL-31 in psoriatic arthritis: A correlation with Th17 cytokine profile.

The goals of our study were to determine the possible association of interleukin (IL)-31 with Th17 cytokine profile in serum and to quantify retinoic acid-related orphan receptor C (RORC) mRNA expression in psoriatic arthritis (PsA) patients. This cross-sectional study was conducted in 50 patients with PsA and 30 control subjects (CS) matched by age and gender. The cytokine serum levels were quantified by magnetic bead-based assay using the Bio-Plex MAGPIX system, and RORC mRNA expression was determined by quantitative polymerase chain reaction (qPCR). As a result, significant differences in IL-31 were observed between study groups (77.23 pg/mL in PsA vs 64.4 pg/mL in CS, P < 0.001) and Th17 cytokine profile serum levels (IL-17A: 6.36 pg/mL in PsA vs 2.97 pg/mL in CS, P = 0.02; IL-17F: 44.15 pg/mL in PsA vs 23.36 pg/mL in PsA, P = 0.01; IL-17E: 3.03 pg/mL in PsA vs 0.82 pg/mL in CS, P < 0.001; IL-21: 36.45 pg/mL in PsA vs 12.44 pg/mL in CS, P = 0.02); however, significant differences were not observed for IL-23 (31.2 pg/mL in PsA vs 53.26 pg/mL in CS, P = 0.58). Furthermore, positive correlations between IL-31 and Th17 cytokine profile serum levels were found (IL-17A: rs = 0.64, P < 0.001; IL-17F: rs = 0.73, P < 0.001; IL-17E: rs = 0.70, P < 0.001; IL-21: rs = 0.54, P = 0.002; IL-23: rs = 0.5, P < 0.01). Regarding RORC gene expression, the PsA group showed an increase of 6.85-fold compared to the CS group. We did not find any association between the serum levels of cytokines and RORC gene expression. In conclusion, in PsA, there are increased serum levels of IL-31, IL-17A, IL-17F, IL-17E, and IL-21, but not IL-23. Moreover, there was a positive correlation of IL-31 with the Th17 cytokine profile and a high RORC gene expression. Altogether, these findings suggest a proinflammatory contribution of IL-31 in close association with the Th17 cytokine profile in PsA.

Damage Evolution and Fracture Events Sequence Analysis of Core-Shell Nanoparticle Modified Bone Cements by Acoustic Emission Technique.

In this research, damage in bone cements that were prepared with core-shell nanoparticles was monitored during four-point bending tests through an analysis of acoustic emission (AE) signals. The core-shell structure consisted of poly(butyl acrylate) (PBA) as rubbery core and methyl methacrylate/styrene copolymer (P(MMA-co-St)) as a glassy shell. Furthermore, different core-shell ratios 20/80, 30/70, 40/60, and 50/50 were prepared and incorporated into the solid phase of the bone cement formulation at 5, 10, and 15 wt %, respectively. The incorporation of a rubbery phase into the bone cement formulation decreased the bending strength and bending modulus. The AE technique revealed that the nanoparticles play an important role on the fracture mechanism of the bone cement, since a higher amount of AE signals (higher amplitude and energy) were obtained from bone cements that were prepared with the nanoparticles in comparison with those without nanoparticles (the reference bone cement). The SEM examination of the fracture surfaces revealed that all of the bone cement formulations exhibited stress whitening, which arises from the development of crazes before the crack propagation. Finally, the use of the AE technique and the fracture surface analysis by SEM enabled insight into the fracture mechanisms that are presented during four-point bending test of the bone cement containing nanoparticles.

Does intensive feeding frequency affect growth performance of common snook Centropomus undecimalis (Bloch, 1792)? / A utilização de frequência alimentar elevada pode afetar o desempenho produtivo do robalo flecha Centropomus undecimalis (Bloch, 1792)?

Abstract Salt water recirculation systems using automatic feeders are a new frontier for marine aquaculture. It is possible to decrease the vulnerability of the traditional fish farming in open systems and reduce wasteful feeding and discharge of effluents, as well as increase the economic returns. An experiment with common snook fingerings (4.31 ± 1.42 g and 8.4 ± 1.0 cm) was performed. Three feeding treatments were evaluated: six, twelve and eighteen feeding times per day. Each treatment had three replications. Among the three tested frequencies (fed 6, 12 and 18 times a day), the feeding frequency of 12 times per day (every two hours) showed the best values of the parameters evaluated for production performance. The final weight values, condition factor, specific growth rate and daily weight gain of the treatment 12 feeding times per day were all significantly higher than the lower and higher frequencies. Our results demonstrate that high feeding frequency is not synonymous of higher performance, but is extremely necessary to find out the best range for the target species. Besides, this relationship between feeding frequency and growth performance might change over weight range. Therefore, future studies should address higher weight ranges for comparison to our results.

Resumo Sistemas de recirculação de água salgada utilizando alimentadores automáticos são uma nova fronteira para a aquicultura marinha. Possibilitam diminuir a vulnerabilidade dos cultivos em sistemas abertos e conferir redução de desperdício de ração e lançamento de efluentes, assim como elevar o retorno econômico. Foi realizado um experimento com juvenis de Robalo-flecha (4,31 ± 1,42 g e 8,4 ± 1,0 cm). Três frequências alimentares foram avaliadas: alimentação seis vezes ao dia; doze vezes ao dia, e; dezoito vezes ao dia. Cada tratamento teve três repetições. Dentre as três frequências avaliadas a frequência alimentar de 12 vezes ao dia foi a que apresentou os melhores valores para os parâmetros zootécnicos avaliados. Os valores obtidos de peso final, fator de condição, taxa de crescimento específico e ganho de peso diário foram todos maiores para a frequência de 12 vezes ao dia do que os obtidos para as frequências maior e menor. Nossos resultados demonstram que elevadas frequências alimentares não são sinônimo de melhor desempenho produtivo, mas é extremamente importante conhecer a frequência ideal para a espécie a ser cultivada. Além disto, a relação entre frequência alimentar e crescimento pode mudar de acordo com a faixa de peso dos indivíduos. Desta forma, é extremamente importante que trabalhos futuros avaliem as frequências aqui estudadas para comparar os resultados em indivíduos maiores.

Resistance to insect pests in wheat-rye and Aegilops speltoides Tausch translocation and substitution lines.

Various insect pests attack wheat (Triticum aestivum L.) that can cause significant grain yield losses to the crop. Farmers usually depend on pesticides, however, smallholder farmers often have limited and ill-timed access to control methods, including insecticides. Host plant resistance is an alternative to protect grain yield and reduce costs to farmers. Three of the most serious pests of wheat are Diuraphis noxia (Kurdjumov), Mayetiola destructor (Say), and Cephus pygmeaus L. These pests occur in most of the wheat growing areas. However, they are of high importance in North Africa and West Asia. The aim of this study was to evaluate a set of wheat-alien translocations for resistance against D. noxia, M. destructor and C. pygmeaus. Genotypes of this germplasm set have already been reported to carry resistance against certain wheat aphid species. Genotypes 1RSam.1AL and MA1S.1RLe(1B), displayed high levels of resistance against D. noxia and C. pygmeaus, respectively. While three genotypes showed resistance reaction against M. destructor: 1Re(1D), 7A.7S-L5, and 7A.7S-Gb5. Except for the resistant genotype to C. pygmeaus, the other four genotypes were previously reported to carry resistance against Sitobion avenae Fabricius, Rhopalosiphum padi L. and Schizaphis graminum (Rondani). These five wheat-alien translocations are currently being used in the bread-wheat breeding programs at CIMMYT and ICARDA to transfer the multiple pest resistance in elite germplasm.

Does intensive feeding frequency affect growth performance of common snook Centropomus undecimalis (Bloch, 1792)?

Salt water recirculation systems using automatic feeders are a new frontier for marine aquaculture. It is possible to decrease the vulnerability of the traditional fish farming in open systems and reduce wasteful feeding and discharge of effluents, as well as increase the economic returns. An experiment with common snook fingerings (4.31 ± 1.42 g and 8.4 ± 1.0 cm) was performed. Three feeding treatments were evaluated: six, twelve and eighteen feeding times per day. Each treatment had three replications. Among the three tested frequencies (fed 6, 12 and 18 times a day), the feeding frequency of 12 times per day (every two hours) showed the best values of the parameters evaluated for production performance. The final weight values, condition factor, specific growth rate and daily weight gain of the treatment 12 feeding times per day were all significantly higher than the lower and higher frequencies. Our results demonstrate that high feeding frequency is not synonymous of higher performance, but is extremely necessary to find out the best range for the target species. Besides, this relationship between feeding frequency and growth performance might change over weight range. Therefore, future studies should address higher weight ranges for comparison to our results.

Mutant p53 gain of function induces HER2 over-expression in cancer cells.

BACKGROUND: HER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of HER2-amplifying tumors carry germline mutations of p53. The mechanisms responsible for the acquisition of oncogenic functions of p53 mutant proteins (mtp53), known as Gain of Function (GOF), over HER2 expression have not been reported. The objective of this study was to evaluate a possible relationship between p53 mutants and HER2 regulation. METHODS: HER2 expression (transcription and protein), as well as HER2 protein stabilization have been evaluated after inducing or silencing of p53 mutants' expression in cell lines. Finally, we evaluated the interaction of the p53 mutants over the HER2 receptor promoter. RESULTS: Higher HER2 expression in cell lines harboring endogenous mtp53 compared with wt or null expression of p53 cell lines. Transfection of p53 mutants (R248Q and R273C) in cell lines increased the expression of HER2. Silencing of p53 mutants, decrease HER2 expression. The p53 mutants R248Q and R273C significantly increase the luciferase activity on the HER2 promoter, and both mutants also promote acetylation of H3 and H4 histones binding in it. CONCLUSIONS: These findings show for the first time that p53 mutants induce over-expression of HER2 at transcriptional level of the HER2 protein. Our results could have clinical implications in breast cancer and other types of cancer where HER2 is over-expressed and used as a therapy target.

Identification of serotoninergic system components in stallion sperm.

Assisted reproductive techniques have been used on several domestic animals to preserve desirable traits in strains of high genetic and commercial value; however in equines its efficiency rate is relatively low. To increase the conception ratio in stallions, some research groups have used pharmacological treatments which promote sperm hyperactivation in order to increase male's fertility rates. In this way, our previous work suggests that serotonin (5-HT) could be a good pharmacological candidate that facilitates conception rate in domestic horses. 5-HT is a neurohormone involved in several reproductive processes, i.e., it enhances hyperactivation, motility, and promotes the acrosome reaction in mammalian sperm, but it has not been described in the stallion sperm yet. Therefore, using both immunofluorescence and western blot techniques, we searched for and found some serotonin markers such as 5-HT, 5-HT1B, 5-HT2A, 5-HT3 receptors, both TPH1 and MAOA enzymes, and serotonin transporter (5-HTT) in stallion sperm. In addition, we found a non-neuroendocrine cell, V-MAT1 transporter, which has not been previously reported in mammalian sperm. Our results suggest that serotoninergic system is present in stallion sperm, which could be a pharmacological target to increase the conception rates in domestic horses.

Resveratrol decreases Rad51 expression and sensitizes cisplatin­resistant MCF­7 breast cancer cells.

Resveratrol (RES), a polyphenol compound with anti­proliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the anti­proliferative effects of cisplatin (CIS) on MCF­7 cells, focusing on the inhibitory effects on DNA repair of double­strand breaks (DSBs). Chemoresistant MCF­7 cells (MCF­7R) were generated by continuous exposure to low concentrations of CIS (10 µM CIS­IC40) during 5 passages, with the IC50 value increasing ~3­fold. Using an MTT assay, we estimated the changes in IC50 for CIS in MCF­7, T47­D, MDA­MB­231 and MCF­7R cells in the presence of RES. The relative transcript level of Nbs­1, Mre­11 and Rad­50 genes was assessed using RT­qPCR analysis. Rad51 and H2AX [pSer139] protein expression was determined by western blot analysis. RES at 50 and 100 µM significantly enhanced the anti­proliferative effects of CIS in both MCF­7 and MCF­7R cells, decreasing the IC50 values for CIS to one­tenth and one­sixth, respectively. A total of 100 µM RES decreased the relative transcript levels of homologous recombination (HR) initiation complex components and the Rad51 protein level in MCF­7 and MCF­7R cells. After 48 h of CIS DNA damage, the levels of Rad51 protein increased, but this effect was inhibited by 100 µM RES. RES also maintained serine 139 phosphorylation of histone H2AX, suggesting that RES prevents the repair of DSBs. It was observed that RES exerts an antagonistic effect over CIS on the activation of Rad51 and sustained phosphorylation of H2AX. The results suggest that RES in combination with DNA damage­based therapy has potential as a strategy to overcome resistance and provide much safer and more effective treatment for breast cancer.

Expression of MIF and TNFA in psoriatic arthritis: relationship with Th1/Th2/Th17 cytokine profiles and clinical variables.

Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = - 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.

Genetic Gains for Grain Yield in CIMMYT's Semi-Arid Wheat Yield Trials Grown in Suboptimal Environments.

Wheat (Triticum aestivum L.) is a major staple food crop grown worldwide on >220 million ha. Climate change is regarded to have severe effect on wheat yields, and unpredictable drought stress is one of the most important factors. Breeding can significantly contribute to the mitigation of climate change effects on production by developing drought-tolerant wheat germplasm. The objective of our study was to determine the annual genetic gain for grain yield (GY) of the internationally distributed Semi-Arid Wheat Yield Trials, grown during 2002-2003 to 2013-2014 and developed by the Bread Wheat Breeding program at the CIMMYT. We analyzed data from 740 locations across 66 countries, which were classified in low-yielding (LYE) and medium-yielding (MYE) environments according to a cluster analysis. The rate of GY increase (GYC) was estimated relative to four drought-tolerant wheat lines used as constant checks. Our results estimate that the rate of GYC in LYE was 1.8% (38.13 kg ha-1 yr-1), whereas in MYE, it was 1.41% (57.71 kg ha-1 yr-1). The increase in GYC across environments was 1.6% (48.06 kg ha-1 yr-1). The pedigrees of the highest yielding lines through the coefficient of parentage analysis indicated the utilization of three primary sources-'Pastor', 'Baviacora 92', and synthetic hexaploid derivatives-to develop drought-tolerant, high and stably performing wheat lines. We conclude that CIMMYT's wheat breeding program continues to deliver adapted germplasm for suboptimal conditions of diverse wheat growing regions worldwide.

[Bacteriobilia: a non-resolved problem]. / Bacteriobilia: un problema sin resolver.

Bile duct is usually sterile, and the isolating of microorganisms (bacteriobilia) has been related to some factors, such as age, biliary drainage before pancreatic surgery or bile duct stones. Gramnegative strains remain the most frequent pathogens, especially Escherichia coli. Among grampositives Enterococcus spp should be mentioned. Currently, there is controversy about whether the presence of bacteriobilia has an impact on unfavorable outcome of biliary disease or surgical procedures or mortality rates, with complications such as surgical site infections or bacteremia. In high-risk patients, such as immunosuppressed or those underwent pancreaticoduodenectomy, bile duct cultures performed routinely, even if there are not clinical data of infection, could be necessary in order to start antibiotic treatment or to reduce its spectrum.

[Role of bacteriobilia in postoperative complications]. / Papel de la bacteriobilia en las complicaciones postoperatorias.

OBJECTIVE: At present there is a controversy regarding the impact of positive bile cultures on morbidity and mortality rates, and on the incidence of readmissions in patients with biliar disease. The aim of this study was to evaluate the role of bacteriobilia in postoperatory infections, mortality or readmissions in these patients. METHODS: The information was obtained from all patients with bile cultures admitted to Hospital Universitario Marqués de Valdecilla (Santander, Spain) from January to December 2011. Clinical, epidemiological and microbiological data and laboratory findings were analyzed. The patients were followed for two years. RESULTS: One hundred and fifty-two patients (65% men) were included. Mean age was 67 years (SD= 15 years). The most frequent diagnoses were acute cholecystitis (79%) and cholangitis (8%). Laparoscopic cholecystectomy was performed in 42% of patients, open cholecystectomy in 45% and percutaneous cholecystostomy in 8%. Bacteriobilia was present in 83 patients (55%). The most frecuent microorganisms isolated were Escherichia coli (31%), Enterococcus faecium (13%) and Klebsiella pneumoniae (13%). The initial antimicrobial agent was a carbapenem in 62 patients (44%) and piperacillin-tazobactam in 28 (18%). There were 39 postoperative infections (26%), 21 readmissions (14%) and 17 patients died during admission (11%). The presence of microorganisms in bile cultures was not a statistically significant predictor of neither complications nor readmissions. CONCLUSIONS: Intra-operative bile cultures would allow guide early appropriate antibiotic treatment use in case of infection, or empiric antimicrobial therapy, however there was no correlation between bacteriobilia and postoperative infections, length of stay, mortality or readmissions.