Diethyl phthalate enhances expression of SIRT1 and DNMT3a during apoptosis in PC12 cells

Diethyl phthalate (DEP) works as a phthalate plasticizer and is ubiquitously used in personal care products, cosmetics, medical equipment and pharmaceutical coating. DEP is considered a potential endocrine disruptor. Previously we found DEP-enhanced apoptosis induced by serum deprivation in PC12 cells. However, the relationship between DEP and longevity-related factors, sirtuins and epigenetic factors (e.g. DNA methyltransferases) remains unclear, because genome modification caused by chemical toxicity, sirtuins and epigenetic factors have played key roles in abnormal metabolism and development. Here, we investigate whether DEP affects sirtuins (SIRT1 and SIRT2) and methyltranferases (DNMT1 and DNMT3a) on the apoptosis of PC12 cells. We found that DNMT3a was significantly decreased by serum deprivation. However, DNMT3a, DNMT3b and SIRT1 were significantly increased under the enhancement of apoptosis induced by serum deprivation. These results suggest that SIRT1, DNMT3a and DNMT3b play multiple and complex roles in different apoptotic stages. Our results showed DEP triggered epigenetic factors on PC12 cells apoptosis under nutrition stress. Finally, our results suggest that monitoring epigenetic factors such as DNMT3a, DNMT3b and SIRT1 could be a useful tool for chemical toxicity risk assessment

Behavior of Solutions of the Hodgkin-Huxley Equations and its Relation to Properties of Mechanoreceptors

The membrane current in the Hodgkin-Huxley equations is considered to be a stimulus to the membrane and the responses to the simulus are numerically calculated. Responses of the Hodgkin-Huxley model to an alternating current superimposed upon a constant bias current show qualitative analogy to responses of biological mechanoreceptors. The intensity of the bias current seems to correspond to the degree of adaptation of actual receptors

Subsurface bacterial growth and grazing impact revealed by an in situ experiment in a shallow aquifer

出版者版タイトル：Active Bacterial Populations and Grazing Impact Revealed by an In Situ Experiment in a Shallow Aquiferautho

Longitudinal monitoring of KRAS-mutated circulating tumor DNA enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer.

BACKGROUND:Liquid biopsies enable the detection of circulating tumor DNA (ctDNA). However, the clinical significance of KRAS-mutated ctDNA for pancreatic cancer has been inconsistent with respect to its prognostic and predictive potential. METHODS AND FINDINGS:A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS mutation in tissues and KRAS ctDNA levels in plasma were determined by RASKET and droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and for evaluating therapeutic responses to chemotherapy compared with carbohydrate antigen 19-9 (CA19-9). In 67 tumor tissues, discrepancies in point mutations of KRAS were rarely observed among individual patients, implying that one targeted point mutation of KRAS can be determined in tumor tissues prior to longitudinal blood monitoring. One-time blood assessment of KRAS-mutated ctDNA before surgery or chemotherapy was not clearly associated with recurrence and prognosis. Sequential blood monitoring was performed in 39 patients who underwent surgery for potentially resectable tumors. Increased CA19-9 levels were significantly associated with recurrence, but not prognosis (P<0.001, P = 1.0, respectively), whereas emergence of KRAS ctDNA was significantly associated with prognosis (P<0.001) regardless of recurrence. Furthermore, in 39 patients who did not undergo surgery, detection of KRAS ctDNA was a predictive factor for prognosis (P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA was the only independent prognostic factor regardless of tumor resection (hazard ratios = 54.5 for patients who underwent surgery and 10.1 for patients who did not undergo surgery; P<0.001 for both). Patients without emergence of KRAS ctDNA within 1 year after surgery showed significantly better prognosis irrespective of recurrence (P<0.001). No detection or disappearance of KRAS ctDNA within 6 months of treatment was significantly correlated with therapeutic responses to first-line chemotherapy (P<0.001). Changes in KRAS status provided critical information for the prediction of therapeutic responses. CONCLUSIONS:Our study showed for the first time that detection of KRAS ctDNA levels within a short period enables the prediction of prognosis and therapeutic responses in patients with pancreatic cancer