Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role.

An abnormal acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network fuels colon cancer progression, endowing cells with invasive and migratory properties. Therapies against this metabolic network may be useful to improve clinical outcomes. Because micro-RNAs (miRNAs/miRs) are important epigenetic regulators, we investigated novel miRNAs targeting this pro-tumorigenic axis; hence to be used as therapeutic or prognostic miRNAs. Thirty-one putative common miRNAs were predicted to simultaneously target the three enzymes comprising the ACSL/SCD network. Target validation by quantitative RT-PCR, Western blotting, and luciferase assays showed miR-544a, miR-142, and miR-19b-1 as major regulators of the metabolic axis, ACSL/SCD Importantly, lower miR-19b-1 expression was associated with a decreased survival rate in colorectal cancer (CRC) patients, accordingly with ACSL/SCD involvement in patient relapse. Finally, miR-19b-1 regulated the pro-tumorigenic axis, ACSL/SCD, being able to inhibit invasion in colon cancer cells. Because its expression correlated with an increased survival rate in CRC patients, we propose miR-19b-1 as a potential noninvasive biomarker of disease-free survival and a promising therapeutic miRNA in CRC.

Polymorphisms in ABCB1 and CYP19A1 genes affect anastrozole plasma concentrations and clinical outcomes in postmenopausal breast cancer patients.

AIMS: Anastrozole, an aromatase inhibitor widely used in breast cancer, has recently been indicated to be a P-glycoprotein (ABCB1) substrate. We have aimed to determine whether ABCB1 single-nucleotide polymorphisms (SNPs) can affect anastrozole plasma concentrations in these patients. In addition, we assessed the impact of SNPs in CYP19A1 and TCL1A on the development of arthralgia and cancer recurrence in our series. METHODS: This study included 110 postmenopausal women with hormone receptor-positive breast cancer. Anastrozole plasma levels were determined by a liquid chromatography-electrospray ionization-quadrupole-time-of-flight mass spectrometry system. Patients were genotyped for SNPs in the ABCB1, TCL1A and CYP19A1 genes to search for associations with pharmacokinetic and pharmacodynamics parameters using logistic regression models. RESULTS: Anastrozole concentrations showed an almost nine-fold interindividual variability (mean 26.95 ± 11.91 ng ml-1 ). The ABCB1 2677-TT genotype was associated with higher plasma levels (32.22 ± 12.82 vs. 25.86 ± 11.56 ng ml-1 for GG/GT subjects; 95% confidence interval: -12.3 to -0.40), whilst the 3435-TT genotype showed a protective effect on the risk of arthralgia (odds ratio = 0.32 [0.11-0.89]; P = 0.029). The CYP19A1 rs1008805 GG genotype was strongly and inversely associated with arthralgia (odds ratio = 0.24 [0.09-0.65], P = 0.004); however, SNPs near the TCL1A gene were not linked to this adverse effect. None of the patients who had cancer recurrence harboured the CYP19A1 rs727479 AA genotype, which, in contrast, was present in 38% of patients who did not relapse (P for trend = 0.031). CONCLUSION: Our findings indicate that variability in anastrozole plasma levels may be attributable to the status of the ABCB1 gene locus. Furthermore, genetic variants in CYP19A1 were associated with arthralgia and cancer recurrence in our patients.

Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals.

Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2 (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical activity has been deeply characterized in Xenopus, its specific relevance during the progression of mitosis is not fully understood. By using a conditional knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is essential for mouse embryonic development and cell cycle progression. Yet, Greatwall-null cells enter into mitosis with normal kinetics. However, these cells display mitotic collapse after nuclear envelope breakdown (NEB) characterized by defective chromosome condensation and prometaphase arrest. Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1-dependent manner before NEB. This export occurs after the nuclear import of cyclin B-Cdk1 complexes, requires the kinase activity of Greatwall, and is mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The mitotic collapse observed in Greatwall-deficient cells is partially rescued after concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic before NEB. These data suggest that Greatwall is an essential protein in mammals required to prevent mitotic collapse after NEB.

The ellagic acid derivative 4,4'-di-O-methylellagic acid efficiently inhibits colon cancer cell growth through a mechanism involving WNT16.

Ellagic acid (EA) and some derivatives have been reported to inhibit cancer cell proliferation, induce cell cycle arrest, and modulate some important cellular processes related to cancer. This study aimed to identify possible structure-activity relationships of EA and some in vivo derivatives in their antiproliferative effect on both human colon cancer and normal cells, and to compare this activity with that of other polyphenols. Our results showed that 4,4'-di-O-methylellagic acid (4,4'-DiOMEA) was the most effective compound in the inhibition of colon cancer cell proliferation. 4,4'-DiOMEA was 13-fold more effective than other compounds of the same family. In addition, 4,4'-DiOMEA was very active against colon cancer cells resistant to the chemotherapeutic agent 5-fluoracil, whereas no effect was observed in nonmalignant colon cells. Moreover, no correlation between antiproliferative and antioxidant activities was found, further supporting that structure differences might result in dissimilar molecular targets involved in their differential effects. Finally, microarray analysis revealed that 4,4'-DiOMEA modulated Wnt signaling, which might be involved in the potential antitumor action of this compound. Our results suggest that structural-activity differences between EA and 4,4'-DiOMEA might constitute the basis for a new strategy in anticancer drug discovery based on these chemical modifications.

Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells.

Breast cancer is the leading cause of cancer-related mortality among females worldwide, and therefore the development of new therapeutic approaches is still needed. Rosemary (Rosmarinus officinalis L.) extract possesses antitumor properties against tumor cells from several organs, including breast. However, in order to apply it as a complementary therapeutic agent in breast cancer, more information is needed regarding the sensitivity of the different breast tumor subtypes and its effect in combination with the currently used chemotherapy. Here, we analyzed the antitumor activities of a supercritical fluid rosemary extract (SFRE) in different breast cancer cells, and used a genomic approach to explore its effect on the modulation of ER-α and HER2 signaling pathways, the most important mitogen pathways related to breast cancer progression. We found that SFRE exerts antitumor activity against breast cancer cells from different tumor subtypes and the downregulation of ER-α and HER2 receptors by SFRE might be involved in its antitumor effect against estrogen-dependent (ER+) and HER2 overexpressing (HER2+) breast cancer subtypes. Moreover, SFRE significantly enhanced the effect of breast cancer chemotherapy (tamoxifen, trastuzumab, and paclitaxel). Overall, our results support the potential utility of SFRE as a complementary approach in breast cancer therapy.

Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway.

Many mammalian transcripts contain target sites for multiple miRNAs, although it is not clear to what extent miRNAs may coordinately regulate single genes. We have mapped the interactions between down-regulated miRNAs and overexpressed target protein-coding genes in murine and human lymphomas. Myc, one of the hallmark oncogenes in these lymphomas, stands out as the up-regulated gene with the highest number of genetic interactions with down-regulated miRNAs in mouse lymphomas. The regulation of Myc by several of these miRNAs is confirmed by cellular and reporter assays. The same approach identifies MYC and multiple Myc targets as a preferential target of down-regulated miRNAs in human Burkitt lymphoma, a pathology characterized by translocated MYC oncogenes. These results indicate that several miRNAs must be coordinately down-regulated to enhance critical oncogenes, such as Myc. Some of these Myc-targeting miRNAs are repressed by Myc, suggesting that these tumors are a consequence of the unbalanced activity of Myc versus miRNAs.

Clipping for endoscopic perforations: initial success but late complication requiring surgery.

INTRODUCTION: This response discusses the article by Kim and colleagues entitled "endoscopic clip closure versus surgery for the treatment of iatrogenic colon perforations developed during diagnostic colonoscopy: a review of 115,285 patients". Iatrogenic colonoscopic perforation, although uncommon, implies serious management problems for endoscopists and surgeons. Nonoperative treatment currently is recommended under certain conditions, and endoscopic clips can primarily close iatrogenic perforations, helping to avoid surgery. Of the 27 colonoscopic perforation cases presented in the article by Kim and colleagues, 16 were managed by endoscopic clipping closure and 11 by primary surgery. Conservative treatment failed for three patients. Only perforation size obtained statistical significance among the nine variables contrasted between the 11 cases with primary surgery and the 13 cases with successful endoscopic clipping. The results for the three patients whose endoscopic closure failed are not reported. AUTHORS' OPINION: The authors of this letter think it would have been interesting if these three patients had been included in the analysis due to the high importance of discovering factors that can predict failure of endoscopic clipping for perforations. CONCLUSIONS: To call attention to possible late complications requiring surgery even when initial conservative management of endoscopic perforation succeeds, the authors of this letter present a case of a colocutaneous (actually, sigmoid-scrotal) fistula in a patient 2 weeks after an apparently successful closure of colonoscopic perforation with an "over-the-scope" clip.

Seroprevalence and coprological prevalence of liver fluke Fasciola hepatica in cattle and sheep from Santander department, Colombia.

Fasciola hepatica is a parasite with a worldwide distribution that affects several mammals, including humans, and is considered a public health problem. Therefore, the aim of this study was to determine the prevalence of Fasciola hepatica in humans, cattle and sheep, as well as to evaluate factors associated with the prevalence. A total of 185 serum samples from sheep, 290 from cattle, and 114 from humans were collected and processed using an in-house developed ELISA to detect IgG antibodies against F. hepatica. Additionally, 185 stool samples from sheep and 290 from cattle were examined using a Dennis sedimentation technique. Risk factors were analyzed using epidemiological surveys. The overall seroprevalence was 46.5% (86/185) in sheep, 32.5% (94/289) in cattle, and no humans tested positive for the infection. The coprological prevalence was 47.7% (86/180) in sheep and 33.7% (98/290) in cattle. Female gender and cattle living with alternate grazing management showed 2.5 and 6.5 times higher probability of infection, respectively. Bovines coexisting with sheep exhibited a higher risk of infection (odds ratio [OR]=4.3) compared to those without sheep. We concluded that F. hepatica in cattle and sheep has an endemic behavior, and therefore represents a problem of public health for rural communities.

High sensitivity flow cytometry immunophenotyping increases the diagnostic yield of malignant pleural effusions.

Diagnosing malignant pleural effusions (MPE) is challenging when patients lack a history of cancer and cytopathology does not detect malignant cells in pleural effusions (PE). We investigated whether a systematic analysis of PE by flow cytometry immunophenotyping (FCI) had any impact on the diagnostic yield of MPE. Over 7 years, 570 samples from patients with clinical suspicion of MPE were submitted for the FCI study. To screen for epithelial malignancies, a 3-color FCI high sensitivity assay was used. The FCI results, qualified as "malignant" (FCI+) or "non-malignant" (FCI-), were compared to integrated definitive diagnosis established by clinicians based on all available information. MPE was finally diagnosed in 182 samples and FCI detected 141/182 (77.5%). Morphology further confirmed FCI findings by cytopathology detection of malignant cells in PE (n = 91) or histopathology (n = 29). Imaging tests and clinical history supported the diagnosis in the remaining samples. The median percentage of malignant cells was 6.5% for lymphoma and 0.23% for MPE secondary to epithelial cell malignancies. FCI identified a significantly lower percentage of EpCAM+ cells in cytopathology-negative MPE than in cytopathology-positive cases (0.02% vs. 1%; p < 0.0001). Interestingly, 29/52 MPE (55.8%) where FCI alerted of the presence of malignant cells were new diagnosis of cancer. Overall, FCI correctly diagnosed 456/522 samples (87.4%) suitable for comparison with cytopathology. These findings show that high sensitivity FCI significantly increases the diagnostic yield of MPE. Early detection of FCI + cases accelerates the diagnostic pathway of unsuspected MPE, thus supporting its implementation in clinical diagnostic work-up as a diagnostic tool.

Dynamics of the nasopharyngeal microbiome of apparently healthy calves and those with clinical symptoms of bovine respiratory disease from disease diagnosis to recovery.

Introduction: Bovine respiratory disease (BRD) is a multifactorial disease complex in which bacteria in the upper respiratory tract play an important role in disease development. Previous studies have related the presence of four BRD-pathobionts (Mycoplasma bovis, Histophilus somni, Pasteurella multocida, and Mannheimia haemolytica) in the upper respiratory tract to BRD incidence and mortalities in the dairy and beef cattle industry, but these studies typically only use one time point to compare the abundance of BRD-pathobionts between apparently healthy and BRD-affected cattle. The objective of this study was to characterize the longitudinal development of the nasopharyngeal (NP) microbiome from apparently healthy calves, and in calves with clinical signs of BRD, the microbiota dynamics from disease diagnosis to recovery. Methods: Deep nasopharyngeal swabs were taken from all calves immediately after transport (day 0). If a calf was diagnosed with BRD (n = 10), it was sampled, treated with florfenicol or tulathromycin, and sampled again 1, 5, and 10 days after antibiotic administration. Otherwise, healthy calves (n = 20) were sampled again on days 7 and 14. Bacterial community analysis was performed through 16S rRNA gene amplicon sequencing. Results: The NP microbiome of the healthy animals remained consistent throughout the study, regardless of time. The NP microbiota beta diversity and community composition was affected by tulathromycin or florfenicol administration. Even though BRD-pathobionts were identified by 16S rRNA gene sequencing in BRD-affected animals, no difference was observed in their relative abundance between the BRD-affected and apparently healthy animals. The abundance of BRD-pathobionts was not predictive of disease development while the relative abundance of BRD pathobionts was unique to each BRD-affected calf. Interestingly, at the end of the study period, the genera Mycoplasma was the most abundant genus in the healthy group, while Lactobacillus was the most abundant genus in the animals that recovered from BRD. Discussion: This study highlights that injected antibiotics seem to improve the NP microbiome composition (higher abundance of Lactobacillus and lower abundance of Mycoplasma), and that the relative abundance of BRD-pathobionts differs between individual calves but is not strongly predictive of BRD clinical signs, indicating that additional factors are likely important in the clinical progression of BRD.

Effects of feeding Saccharomyces cerevisiae fermentation postbiotic on the fecal microbial community of Holstein dairy calves.

BACKGROUND: The livestock industry is striving to identify antibiotic alternatives to reduce the need to use antibiotics. Postbiotics, such as Saccharomyces cerevisiae fermentation product (SCFP), have been studied and proposed as potential non-antibiotic growth promoters due to their effects on animal growth and the rumen microbiome; however, little is known of their effects on the hind-gut microbiome during the early life of calves. The objective of this study was to measure the effect of in-feed SCFP on the fecal microbiome of Holstein bull calves through 4 months of age. Calves (n = 60) were separated into two treatments: CON (no SCFP added) or SCFP (SmartCare®, Diamond V, Cedar Rapids, IA, in milk replacer and NutriTek®, Diamond V, Cedar Rapids, IA, incorporated into feed), and were blocked by body weight and serum total protein. Fecal samples were collected on d 0, 28, 56, 84, and 112 of the study to characterize the fecal microbiome community. Data were analyzed as a completely randomized block design with repeated measures when applicable. A random-forest regression method was implemented to more fully understand community succession in the calf fecal microbiome of the two treatment groups. RESULTS: Richness and evenness of the fecal microbiota increased over time (P < 0.001), and SCFP calves tended to increase the evenness of the community (P = 0.06). Based on random-forest regression, calf age as predicted by microbiome composition was significantly correlated with the calf physiological age (R2 = 0.927, P < 1 × 10-15). Twenty-two "age-discriminatory" ASVs (amplicon sequence variants) were identified in the fecal microbiome that were shared between the two treatment groups. Of these, 6 ASVs (Dorea-ASV308, Lachnospiraceae-ASV288, Oscillospira-ASV311, Roseburia-ASV228, Ruminococcaceae-ASV89 and Ruminoccocaceae-ASV13) in the SCFP group reached their highest abundance in the third month, but they reached their highest abundance in the fourth month in the CON group. All other shared ASVs reached their highest abundance at the same timepoint in both treatment groups. CONCLUSIONS: Supplementation of SCFP altered the abundance dynamics of age discriminatory ASVs, suggesting a faster maturation of some members of the fecal microbiota in SCFP calves compared to CON calves. These results demonstrate the value of analyzing microbial community succession as a continuous variable to identify the effects of a dietary treatment.

The bovine nasal fungal community and associations with bovine respiratory disease.

Introduction: Effective identification and treatment of bovine respiratory disease (BRD) is an ongoing health and economic issue for the dairy and beef cattle industries. Bacteria pathogens Pasteurellamultocida, Mycoplasmabovis, Mannheimia haemolytica, and Histophilus somni and the virus Bovine herpesvirus-1 (BHV-1), Bovine parainfluenza-3 virus (BPIV-3), Bovine respiratory syncytial virus (BRSV), Bovine adenovirus 3 (BAdV3), bovine coronavirus (BoCV) and Bovine viral diarrhea virus (BVDV) have commonly been identified in BRD cattle; however, no studies have investigated the fungal community and how it may also relate to BRD. Methods: The objective of this study was to understand if the nasal mycobiome differs between a BRD-affected (n = 56) and visually healthy (n = 73) Holstein steers. Fungal nasal community was determined by using Internal Transcribed Spacer (ITS) sequencing. Results: The phyla, Ascomycota and Basidiomycota, and the genera, Trichosporon and Issatchenkia, were the most abundant among all animals, regardless of health status. We identified differences between healthy and BRD animals in abundance of Trichosporon and Issatchenkia orientalis at a sub-species level that could be a potential indicator of BRD. No differences were observed in the nasal fungal alpha and beta diversity between BRD and healthy animals. However, the fungal community structure was affected based on season, specifically when comparing samples collected in the summer to the winter season. We then performed a random forest model, based on the fungal community and abundance of the BRD-pathobionts (qPCR data generated from a previous study using the same animals), to classify healthy and BRD animals and determine the agreement with visual diagnosis. Classification of BRD or healthy animals using ITS sequencing was low and agreed with the visual diagnosis with an accuracy of 51.9%. A portion of the ITS-predicted BRD animals were not predicted based on the abundance of BRD pathobionts. Lastly, fungal and bacterial co-occurrence were more common in BRD animals than healthy animals. Discussion: The results from this novel study provide a baseline understanding of the fungal diversity and composition in the nasal cavity of BRD and healthy animals, upon which future interaction studies, including other nasal microbiome members to further understand and accurately diagnose BRD, can be designed.

Persistence of symmetry-protected Dirac points at the surface of the topological crystalline insulator SnTe upon impurity doping.

We investigate the effect of a non-magnetic donor impurity located at the surface of the SnTe topological crystalline insulator. In particular, the changes on the surface states due to a Sb impurity atom are analyzed by means of ab initio simulations of pristine and impurity-doped SnTe. Both semi-infinite and slab geometries are considered within the first-principles approach. Furthermore, minimal and Green's function continuum models are proposed with the same goal. We find that the Dirac cones are shifted down in energy upon doping; this shift strongly depends on the position of the impurity with respect to the surface. In addition, we observe that the width of the impurity band presents an even-odd behavior by varying the position of the impurity. This behavior is related to the position of the nodes of the wave function with respect to the surface, and hence it is a manifestation of confinement effects. We compare slab and semi-infinite geometries within the ab initio approach, demonstrating that the surface states remain gapless and their spin textures are unaltered in the doped semi-infinite system. In the slab geometry, a gap opens due to hybridization of the states localized at opposite surfaces. Finally, by means of a continuum model, we extrapolate our results to arbitrary positions of the impurity, clearly showing a non-monotonic behavior of the Dirac cone.

The Characterization of Cardiac Explants Reveals Unique Fibrosis Patterns and a Predominance of CD8+ T Cell Subpopulations in Patients with Chronic Chagas Cardiomyopathy.

AIM: The present study aimed to characterize the histopathological findings and the phenotype of inflammatory cells in the myocardial tissue of patients with end-stage heart failure (ESHF) secondary to CCC in comparison with ESHF secondary to non-Chagas cardiomyopathies (NCC). METHODS: A total of 32 explanted hearts were collected from transplanted patients between 2014 and 2017. Of these, 21 were classified as CCC and 11 as other NCC. A macroscopic analysis followed by a microscopic analysis were performed. Finally, the phenotypes of the inflammatory infiltrates were characterized using flow cytometry. RESULTS: Microscopic analysis revealed more extensive fibrotic involvement in patients with CCC, with more frequent foci of fibrosis, collagen deposits, and degeneration of myocardial fibers, in addition to identifying foci of inflammatory infiltrate of greater magnitude. Finally, cell phenotyping identified more memory T cells, mainly CD8+CD45RO+ T cells, and fewer transitioning T cells (CD45RA+/CD45RO+) in patients with CCC compared with the NCC group. CONCLUSIONS: CCC represents a unique form of myocardial involvement characterized by abundant inflammatory infiltrates, severe interstitial fibrosis, extensive collagen deposits, and marked cardiomyocyte degeneration. The structural myocardial changes observed in late-stage Chagas cardiomyopathy appear to be closely related to the presence of cardiac fibrosis and the colocalization of collagen fibers and inflammatory cells, a finding that serves as a basis for the generation of new hypotheses aimed at better understanding the role of inflammation and fibrogenesis in the progression of CCC. Finally, the predominance of memory T cells in CCC compared with NCC hearts highlights the critical role of the parasite-specific lymphocytic response in the course of the infection.

Identification of bovine respiratory disease through the nasal microbiome.

BACKGROUND: Bovine respiratory disease (BRD) is an ongoing health and economic challenge in the dairy and beef cattle industries. Multiple risk factors make an animal susceptible to BRD. The presence of Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis in lung tissues have been associated with BRD mortalities, but they are also commonly present in the upper respiratory tract of healthy animals. This study aims to compare the cattle nasal microbiome (diversity, composition and community interaction) and the abundance of BRD pathogens (by qPCR) in the nasal microbiome of Holstein steers that are apparently healthy (Healthy group, n = 75) or with BRD clinical signs (BRD group, n = 58). We then used random forest models based on nasal microbial community and qPCR results to classify healthy and BRD-affected animals and determined the agreement with the visual clinical signs. Additionally, co-occurring species pairs were identified in visually BRD or healthy animal groups. RESULTS: Cattle in the BRD group had lower alpha diversity than pen-mates in the healthy group. Amplicon sequence variants (ASVs) from Trueperella pyogenes, Bibersteinia and Mycoplasma spp. were increased in relative abundance in the BRD group, while ASVs from Mycoplasma bovirhinis and Clostridium sensu stricto were increased in the healthy group. Prevalence of H. somni (98%) and P. multocida (97%) was high regardless of BRD clinical signs whereas M. haemolytica (81 and 61%, respectively) and M. bovis (74 and 51%, respectively) were more prevalent in the BRD group than the healthy group. In the BRD group, the abundance of M. haemolytica and M. bovis was increased, while H. somni abundance was decreased. Visual observation of clinical signs agreed with classification by the nasal microbial community (misclassification rate of 32%) and qPCR results (misclassification rate 34%). Co-occurrence analysis demonstrated that the nasal microbiome of BRD-affected cattle presented fewer bacterial associations than healthy cattle. CONCLUSIONS: This study offers insight into the prevalence and abundance of BRD pathogens and the differences in the nasal microbiome between healthy and BRD animals. This suggests that nasal bacterial communities provide a potential platform for future studies and potential pen-side diagnostic testing.

Glycosylation pattern in the appendix testis in children with cryptorchidism.

In humans, at about week 6, sex cords develop within the forming testes. Testes normally descend to the scrotum; cryptorchidism occurs when one or two testes do not descend to scrotum and in some case are accompanied by the appendix testis. The appendix testis is a small sessile or polypoid structure located at the antero superior pole of the testis, adjacent to the head of the epididymis. Glycans can be involved in development of the appendix testis and cryptorchidism. In this work, lectin histochemistry was used to evaluate glycans expression in appendix testis in children with cryptorchidism. Our results showed that lectin from Lens culinaris, Ulex europaeus I., Canavalia ensiformis, Artocarpus integrifolia, Glycine max, and Griffonia simplicifolia recognizes epithelial and estromal cells. Not interaction was observed with lectin from Amaranthus leucocarpus, while lectin from Dolichus biflorus lectin only recognizes epithelial cells. Our results suggest that O-glycans linked in some glycoproteins represent important elements in appendix testis development.

[Optimization of creatinine measurement for laboratory estimation of glomerular filtration rate]. / Optimización de la creatinina al estimar la tasa de filtración glomerular en el laboratorio.

OBJECTIVE: to analyze the optimization of serum creatinine in the laboratory reports of the estimation of glomerular filtration rate (GFR) in groups of patients who were overweight, obese, hypertensive, or had participated in SOHDI diabetes self-help groups. We also looked at how much the patients had learned about their disease, stress control, diet and exercise, as all the problems have increased risk of kidney disease. METHODS: The serum creatinine results in the Family Medicine Unit No. 34, IMSS, at Jalisco, was analyzed in a transverse study, from January to December of 2008. GFR was estimated with the Cockcroft-Gault formulary. Statistical analysis with multivariate logistic regression analyses was performed. RESULTS: the sample was 8331 patients: 23.5 % with GFR < 60 mL/min/1.73 m(2), and 9.1 % with serum creatinine > 1.5 mg/dL. Associated factors were age < 19 years, woman age 19 to 59 years, and SOHDI. CONCLUSIONS: the study suggested that participating in SOHDI groups, and being women are protective factors for dimunution of GFR. The people < 19 years had lesser GFR.

Replacing dietary antibiotics with 0.20% l-glutamine in swine nursery diets: impact on intestinal physiology and the microbiome following weaning and transport.

Previous research demonstrates that supplementing 0.20% l-glutamine (GLN) in the diets of newly weaned and transported pigs improves growth rate to a similar extent as providing dietary antibiotics (AB). However, research comparing the effects of GLN vs. AB on intestinal physiology and the microbiome is limited. Therefore, the study objective was to compare the effects of supplementing nursery diets with GLN, AB, or no dietary antibiotics (NA) on intestinal physiology and the microbiome of pigs in a production environment following weaning and transport. Mixed-sex piglets (N = 480; 5.62 ± 0.06 kg body weight [BW]) were weaned (18.4 ± 0.2 d of age) and transported for 12 h in central Indiana, for two replicates, during the summer of 2016 and the spring of 2017. Pens were blocked by BW and allotted to one of the three dietary treatments (n = 10 pens/dietary treatment/replicate [8 pigs/pen]): AB (chlortetracycline [441 ppm] + tiamulin [38.6 ppm]), GLN (0.20% as-fed), or NA fed for 14 d. From day 14 to 34, pigs were fed common AB-free diets in two phases. On day 33, villus height:crypt depth tended to be increased (P = 0.07; 7.0%) in GLN and AB pigs vs. NA pigs. On day 33, glucagon-like peptide 2 (GLP-2) mRNA abundance was decreased (P = 0.01; 50.3%) in GLN and NA pigs vs. AB pigs. Crypt depth was increased overall on day 33 (P = 0.01; 16.2%) during the spring replicate compared with the summer replicate. Villus height:crypt depth was reduced (P = 0.01; 9.6%) during the spring replicate compared with the summer replicate on day 33. On day 13, tumor necrosis factor-alpha and occludin mRNA abundance was increased (P ≤ 0.04; 45.9% and 106.5%, respectively) and zonula occludens-1 mRNA abundance tended to be greater (P = 0.10; 19.2%) in the spring replicate compared with the summer replicate. In addition, AB pigs had increased (P = 0.01; 101.3%) GLP-2 mRNA abundance compared with GLN and NA pigs. Microbiome analysis indicated that on day 13, dietary treatment altered the microbiota community structure (P = 0.03). Specifically, the AB pigs tended to be distinct from both the NA and GLN pigs (P = 0.08), and Lactobacillus was increased nearly 2-fold in AB compared with NA pigs (q = 0.04) and GLN pigs (q = 0.22). In conclusion, GLN supplementation tended to improve some morphological markers of intestinal health similarly to AB pigs, while the microbiome composition in GLN pigs was more similar to NA pigs than AB pigs.

O-glycosylation expression in fibroadenoma.

Fibroadenomas are human benign breast tumors characterized by proliferation of epithelial and stroma cells of the terminal ductal unit. Expression of O-glycans seems to contribute to the proliferation and transformation events. With this in mind, we evaluated the expression of glycans in fibroadenoma tissue through immunohistochemistry with antibodies against mucin epitopes (Anti CA15-3 and MUC1), as well as with lectins specific for glycans linked to proteins or lipids, and we compared findings with healthy breast specimens. Our results show positive expression of CA15-3 and MUC1 in fibroadenoma tissue, mainly in duct and stroma cells, whereas, in normal samples, staining was observed in duct cells. The lectin from Glycine max recognized equally well duct and stroma cells; this was the only lectin showing co-localization with anti-CA15-3 in healthy and tumor tissues. Dolichos biflorus, Artocarpus integrifolia, and Griffonia simplicifolia lectins recognized duct cells in control healthy tissues as well as in fibroadenoma tissue. The lectin from Amaranthus leucocarpus recognized only duct cells in control samples, whereas, in fibroadenoma tissue, it recognized duct and some stromal cells, suggesting that O-glycans-type mucin linked to proteins and mucin participate in the development of fibroadenomas.