Zearalenone (ZEA), a secondary metabolite from Fusarium fungi found in cereal-based foods, promotes the growth of colon, breast, and prostate cancers in vitro. However, the lack of animal studies hinders a deeper mechanistic understanding of the cancer promotive effect of ZEA. The aim of this study was to unveil the effect of ZEA on colon cancer progression and its underlying mechanism. Through integrative analyses of transcriptomics, metabolomics, metagenomics, and host phenotypes, we investigated the impact of a 4-week ZEA intervention on colorectal cancer in xenograft mice. Our results showed that a 4-week ZEA intervention increased the tumor weight twofold. ZEA exposure significantly increased the mRNA and protein levels of BEST4, DGKB and KI67, and the phosphorylation levels of ERK1/2 and AKT. Metabolomics analysis of the serum revealed the levels of amino acids, including histidine, arginine, citrulline and glycine decreased significantly in the ZEA group. Furthermore, ZEA lowered the alpha diversity of the gut microbiota and reduced the abundance of 9 genera, such as Tuzzerella and Rikenella, etc. Further association analysis indicated that Tuzzerella was negatively associated with the expression of BEST4 and DGKB genes, serum uric acid level and tumor weight. In addition, circulatory hippuric acid level was positively correlated with the tumor weight and the expression of oncogenic genes, including ROBO3, JAK3 and BEST4. Altogether, our results indicated that ZEA promoted colon cancer tumor progression through enhancing the BEST4/AKT/ERK1/2 pathway, lowering the circulatory amino acid concentration, alternating the gut microbiota composition, and suppressing the SCFA production.
The aim was to test the use of eye-tracking methodology for the early detection of ASD in a task of association between unfamiliar objects and pseudowords. Significant differences were found between ASD (n = 57) and TD (n = 57) Spanish speaking toddlers in the number and time of fixation. The TD children showed more and longer fixations on eyes and mouth while the ASD children attended almost exclusively to objects, making it difficult to integrate lexical and phonological information. Moreover, the TD toddlers looked at the mouth when the pseudoword was produced while the ASD toddlers did not. Gaze fixation on eyes and mouth during word learning recorded by eye-tracking may be used as a biomarker for the early diagnosis of ASD.
Reducing animal handling and costs in timed artificial insemination (TAI) systems are of great interest in animal production, regardless of the species. Thus, this study was carried out to investigate the effects of administering oestradiol cypionate (EC) or hCG to induce ovulation in buffalo (Bubalus bubalis) in TAI programs. The 79 Bufalipso heifers housed at Institute of Animal Science, San José de las Lajas, Cuba, were, on average, 24 months of age with a body weight of 310 to 380 kg at the beginning of the experiment. The investigation was conducted out of the breeding season (25 June through 28 July 2012). Heifers were randomly assigned to 1 of 3 treatment groups; either hCG (control group) or EC1 and EC2, in which TAI was performed at either 48 or 56 h after the EC injection, respectively. On the first day of the treatment regime (Day 0), animals received oestradiol benzoate (2 mg i.m.; Sincrodiol®, Ourofino, Brazil), followed by the insertion of an intravaginal device containing 1 g of progesterone (Primer®, Tecnopec, São Paolo, Brazil). On Day 9, an intramuscular luteolytic dose of cloprostenol (500 μg; Ciosin®, Intervet, Brazil) and eCG (500 UI; Novormon®, Intervet) were given in all heifers along with the removal of the intravaginal device. On the same day, 0.5 mg of EC (ECP®, Pfizer, Brazil) was administered intramuscularly in the EC1and EC2 groups. Animals in the hCG group received hCG (1000 IU i.m.; Vetecor®, Hertape Calier, Spain) on Day 11 and were inseminated 14 h later. Pregnancy diagnosis was performed by ultrasound 35 days after TAI. Data were analysed by a chi-squared test, with P < 0.05 taken as significant. There were no differences among treatment groups, with values of 57.7 (15/26), 60.7 (17/28), and 64% (16/25) for the EC1, EC2, and hCG groups, respectively. In conclusion, oestradiol cypionate was effective at inducing ovulation in buffalo heifers in TAI programs comparable to the control group, as evidenced by the conception rates. In addition, animals subjected to the EC protocol pass just 3 times through the corral instead of 4 when receiving hCG, which decreases the animal handling and costs.
Gap junctions are intercellular channels that mediate cell-to-cell communication, allowing the passage of small signalling molecules. In the ovary, connexin 43 (Cx43) and connexin 37 (Cx37) are important gap junctional proteins expressed in the granulosa and cumulus cells or oocytes of several species. Gap junctions and connexins are required for the regulation of the oocytes meiotic resumption in preovulatory follicles after the surge of LH. However, unlike other species, canine oocytes do not resume meiosis before ovulation, which could be related to expression patterns of Cx43 and Cx37 during oocyte development and ovulation. Therefore, this study aimed to address the canine Cx37 and Cx43 gene expressions throughout the oestrous cycle, including the preovulatory period. The ovaries were obtained from bitches 1-6 years old (n=72) following ovariohysterectomy. The stage of the oestrous cycle was assessed according the ovarian structures and by measurements of serum progesterone (P4) levels obtained from blood samples on the day of surgery. Anestrus was <0.1 ng/mL P4 and absence of follicles or corpus luteum in the ovarian surface; proestrus was 0.2-2 ng/mL P4 and growing small to medium follicles on the surface of the ovaries; oestrus was 2-19 mg/mL P4 and large follicles on the surface of the ovaries; and diestrus was >20 ng/mL P4 and mainly predominant corpus luteum on the ovaries. For Cx43 analysis, follicular cells (granulosa and theca) were mechanically recovered from follicles (n=620) distributed into 4 types: prenatal (1 layer of granulosa cells up to the onset of antrum formation), small antral (~0.2-0.39mm), medium antral (~0.4-5.9mm), and large antral (~6-10mm). For Cx37 study, the cumulus-oocytes complexes (COC) from the same follicles were used. Total RNA extraction was performed, and the evaluation of gene expression levels was achieved by relative quantification quantitative PCR analysis in follicular cells and COC. The data from at least 3 independent experiments for each gene were evaluated by ANOVA. The gene expression of both Connexins were observed in all stages of follicular development; however, the mRNA levels varied over the oestrous cycle. Both Cx43 and Cx37 transcripts showed the highest (P<0.05) levels at anestrus when compared to other phases. The mRNA levels of both genes remained without changes in large follicles at oestrus stage, suggesting that, in contrast to other mammals where LH down-regulates connexins expression leading to the subsequent loss of intercellular coupling, the communication between the oocyte and follicular cells was maintained in canines. In conclusion, these 2 connexin genes were differentially expressed in canine follicular cells and COC during the follicular development. The maintenance of the gene expression of these connexins at the final follicular growth may be involved in the prolonged meiotic arrest in this species. Supported by Ga grant from FONDECYT (1171670).
Las cifras de víctimas de violencia sexual en niños, niñas y adolescentes (N.N.A) en Colombia, sigue en aumento; a pesar de los esfuerzos de las autoridades de protección integral de N.N.A en el país. Así este artículo, aborda la problemática estudiada con el objetivo de diseñar estrategias de acción preventiva policial contra la violencia sexual en menores de edad en Colombia, partiendo del análisis de los factores que inciden en estos delitos. El marco de referencia se trazó desde familia, N.N.A, violencia sexual, y entornos de protección; también del análisis de ponentes expertos, en el “Congreso Internacional Contra los Fenómenos Criminales que Afectan la Niñez”; igualmente de la Encuesta -EVCNNA. La metodología descriptiva con enfoque cualitativo; permitió encontrar que la población con mayor afectación de violencia sexual en Colombia son niños, de 12 a17 años con una tasa del 80%; y los delitos de pornografía con menores, y explotación sexual y comercial se elevan a un 88%; para finalmente concluir que en el hogar y en especial los familiares más cercanos, son los principales perpetradores de abusos sexuales contra N.N.A. en Colombia.
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