Cellular density‐dependent increases in HIF‐1α compete with c‐Myc to down‐regulate human EP4 receptor promoter activity through Sp‐1‐binding region

The up‐regulated expression of E‐type prostanoid (EP) 4 receptors has been implicated in carcinogenesis; however, the expression of EP4 receptors has also been reported to be weaker in tumor tissues than in normal tissues. Indeed, EP4 receptors have been suggested to play a role in the maintenance of colorectal homeostasis. This study aimed to examine the underlying mechanisms/reasons for why inconsistent findings have been reported regarding EP4 receptor expression levels in homeostasis and carcinogenesis by focusing on cellular densities. Thus, the human colon cancer HCA‐7 cells, which retain some functional features of normal epithelia, and luciferase reporter genes containing wild‐type or mutated EP4 receptor promoters were used for elucidating the cellular density‐dependent mechanisms about the regulation of EP4 receptor expression. In silico analysis was also utilized for confirming the relevance of the findings with respect to colon cancer development. We here demonstrated that the expression of EP4 receptors was up‐regulated by c‐Myc by binding to Sp‐1 under low cellular density conditions, but was down‐regulated under high cellular density conditions via the increase in the expression levels of HIF‐1α protein, which may pull out c‐Myc and Sp‐1 from DNA‐binding. The tightly regulated EP4 receptor expression mechanism may be a critical system for maintaining homeostasis in normal colorectal epithelial cells. Therefore, once the system is altered, possibly due to the transient overexpression of EP4 receptors, it may result in aberrant cellular proliferation and transformation to cancerous phenotypes. However, at the point, EP4 receptors themselves and their mediated homeostasis would be no longer required

The effects of perioperative oral management on perioperative serum albumin levels in patients treated surgically under general anesthesia : A multicenter retrospective analysis in Japan

The purpose of the present study was to investigate the efficacy of perioperative oral managements (POMs) on perioperative nutritional conditions in patients undergoing surgery with general anesthesia. Medical records were retrospectively reviewed and the effects of POMs were investigated based on a large number of cases using a multicenter analysis. The profile of serum albumin levels was assessed and compared between patients with and without POMs using the multivariate analysis. Seventeen Eleven thousand and one hundred sixty patients (4,873 males and 6,287 females) were reviewed. Of these, 2710 patients (24.3%) had undergone POMs. The results of a multivariate analysis revealed the significant positive effect of POMs on perioperative serum albumin level (change between at admission and discharge, (Estimate: 0.022, standard error: 0.012, P < .0001). Patient gender, age, surgical site, performance status, the American Society of Anesthesiologists (ASA) physical status classification, operation time, amount of blood loss, and serum albumin level at admission were also significant predictors. Adjusted multivariate analysis of the effects of POMs on perioperative change of serum albumin level in all subjects reveled the significance of POMs intervention (estimate: 0.022, standard error: 0.012, P < .0001). These results suggest that POMs exerts significant positive effects on perioperative serum albumin levels in patients underwent surgery under general anesthesia

The cysteine-rich domain of TET2 binds preferentially to mono- and dimethylated histone H3K36

Missense mutations in Ten-eleven translocation 2 (TET2) gene are frequently found in leukaemia patients. Although mutations span the entire coding region, they tend to cluster in the C-terminal enzymatic domain and a cysteine-rich (CR) domain of unknown function. Herein, we found the CR domain binds chromatin preferentially at the histone H3 tail by recognising H3 lysine 36 mono- and dimethylation (H3K36me1/2). Importantly, missense mutations in the CR domain perturbed TET2 recruitment to the target locus and its enzymatic activities. Our findings identify a novel H3K36me recognition domain and uncover a critical link between histone modification and DNA hydroxylation in leukaemogenesis

The origin of p40-negative and CDX2-positive primary squamous cell carcinoma of the stomach: case report

Abstract Background Primary gastric squamous cell carcinoma (SCC) is a very rare disease. The origin of this tumor remains unclear, although there are some hypotheses. Case summary A 60-year-old man consulted a previous physician complaining of upper abdominal pain. Esophagogastroduodenoscopy revealed type 2 gastric cancer, and the patient was referred to our hospital. After close examination, the patient was diagnosed as cStage IIA gastric adenocarcinoma, and distal gastrectomy was performed. Histochemical studies showed typical findings of SCC, and the tumor was surrounded by intestinal metaplasia. Immunohistochemical examination was positive for cytokeratin (CK) 5/6 and caudal-type homeobox protein 2 (CDX2) and negative for p63/p40. Conclusion The results of immunostaining for CK5/6 supported that this tumor was SCC, but the question why p63/p40 were negative and CDX2 was positive still remained. Concerning about the origin of p63/p40 and CDX2, it was suggested that the tumor cells were not derived from ectopic squamous epithelium but from intestinal metaplasia. And tumor cells looked like homogeneous and squamous metaplasia was not observed. These findings supported the idea that these tumor cells arose from stem cells in the intestinal metaplasia of the stomach

A longitudinal functional neuroimaging study in medication-naïve depression after antidepressant treatment.

Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS) as a tool in assisting the diagnosis of major depressive disorder (MDD); however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC). We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT) following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover, the correlation analysis indicates that the NIRS signals before the initiation of treatment may be a biological marker to predict patient's clinical response to antidepressant treatment. The present study provides further evidence to support a potential application of NIRS for the diagnosis and treatment of depression