NUCKS1 promotes the progression of colorectal cancer via activating PI3K/AKT/mTOR signaling pathway.

Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) is highly expressed in a variety of malignant tumors and functions as an oncogene; however, its role in colorectal cancer (CRC) remains unclear. We aimed to explore the function and regulatory mechanisms of NUCKS1 and potential therapeutic agents targeting NUCKS1 in CRC. We knocked down and overexpressed NUCKS1 in CRC cells and explored its effects in vitro and in vivo. Flow cytometry, CCK-8, Western blotting, colony formation, immunohistochemistry, in vivo tumorigenic, and transmission electron microscopy analyses were performed to determine the effects of NUCKS1 on CRC cell function. LY294002 was used to examine the mechanism of NUCKS1 expression in CRC cells. Potential therapeutic agents for NUCKS1-high CRC patients were analyzed using the CTRP and PRISM datasets, and the function of selected agents was determined by CCK-8 and Western blotting. We revealed that NUCKS1 was highly expressed in CRC tissues and clinically correlated with poor prognosis in CRC patients. NUCKS1 knockdown induces cell cycle arrest, inhibits CRC cell proliferation, and promotes apoptosis and autophagy. These results were reversed when NUCKS1 was overexpressed. Mechanistically, NUCKS1 exerts a cancer-promoting function by activating the PI3K/AKT/mTOR signaling pathway. This was reversed when LY294002 was used to inhibit the PI3K/AKT pathway. Furthermore, we determined that mitoxantrone exhibited high drug sensitivity in NUCKS1-overexpressing CRC cells. This work demonstrated NUCKS1 plays a crucial role in CRC progression via the PI3K/AKT/mTOR signaling pathway. Additionally, mitoxantrone may be a potential therapeutic agent for CRC treatment. Therefore, NUCKS1 represents a promising anti-tumor therapeutic target.

Social hierarchy modulates responses of fish exposed to contaminants of emerging concern.

Many organisms, including the fathead minnow (Pimephales promelas), a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG) axis mainly through regulation of circulating androgen concentrations, which in turn drive the expression of secondary sex characteristics (SSCs). As dominant and subordinate males in an exposure study are initially under different physiological conditions (i.e., differing plasma androgen concentrations), we proposed that they belong to different subpopulations in the context of exposure to compounds that may interact with the HPG axis. Using a meta-analysis of our data from several previously published studies, we corroborated the hypothesis that social status, as indicated by SSCs, results in distinct clusters (eigenvalues >0.8 explaining >80% of variability) with differential expression of plasma vitellogenin, a commonly used biomarker of exposure to contaminants of emerging concern (CEC). Furthermore, we confirmed our predictions that exposure to estrogenic CECs would homogenize plasma vitellogenin response (E1: cluster mean SSC values decreased to 4.33 and 4.86 relative to those of control; E2: decreased to 4.8 and 5.37) across the social hierarchy. In contrast, serotonin-specific reuptake inhibitors expand this response range (cluster mean SSC increased to 5.21 and 6.5 relative to those of control). Our results demonstrated that social hierarchies in male fathead minnows result in heterogeneous responses to chemical exposure. These results represent a cautionary note for the experimental design of single-sex exposure studies. We anticipate our study to be a starting point for the re-evaluation of toxicological data analyses in single sex exposure experiments.

Investigation of treatment methods in obstructive colorectal cancer.

PURPOSE: The aim of this study was to explore the treatment strategies for patients with obstructive colorectal cancer at different sites. METHODS: Treatment strategies were adopted according to the location of colorectal cancer and the condition of the patients when they were admitted to the hospital. Among a total of 134 patients, 29 patients were subjected to stent placement to relieve the obstruction before undergoing colorectal resection, 15 patients underwent per anum ileus catheterization to alleviate the symptoms of obstruction and waited for removal of the tumor within a limited time; 39 underwent intraoperative colonic lavage and colon resection with anastomosis and the remaining 51 patients were subjected to emergency surgery due to strangulation of the bowel, perforation, septic shock or other conditions before surgery. RESULTS: Stent placement was successfully performed on 23 patients, with a success rate of 79%. Ninety-five of 134 patients (71% had stage I anastomosis and only one case had anastomotic fistula. Infection of incision happened in 9 (7%) cases and 2 (1.5%) patients died of infection. CONCLUSIONS: Individualized treatment for patients with obstructive colorectal cancer can lead to tumor resection and stage I anastomosis, thereby avoiding the suffering of second-stage surgery or colostomy.

Anterior tibial artery perforator flap for reconstruction of intraoral defects.

PURPOSE: The present clinical study assessed the feasibility of using an anterior tibial artery perforator (ATAP) flap for the reconstruction of an intraoral defect after ablative surgery for oral cancer. PATIENTS AND METHODS: A cohort of consecutive patients with oral cancer requiring reconstruction of an intraoral defect using an ATAP flap were enrolled after ablative surgery for oral cancer and ipsilateral neck dissection. RESULTS: Twelve patients had primary oral squamous cell carcinoma (8 with tongue cancer and 4 with buccal cancer). All patients received intraoral defect repair using an ATAP flap from the lower left leg. The flap measured 7 × 4 to 8 × 6 cm(2). Flap thickness was approximately 4.8 mm (3 to 6 mm). Anastomosis of all ATAP flaps was straightforward because of the long and high-caliber vessel pedicle. All flaps survived and yielded excellent esthetic results for intraoral reconstruction. No major complications occurred in any patient. CONCLUSION: The main advantages of the ATAP flap included the thin and pliable tissue characteristics and a long and high-caliber pedicle. For small and medium-size intraoral defects, the ATAP flap is a reliable alternative to the radial forearm free flap.