KrasG12D-LOH promotes malignant biological behavior and energy metabolism of pancreatic ductal adenocarcinoma cells through the mTOR signaling pathway.

Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in various tumours. However, the exact function and mechanism by which KrasG12D-LOH operates remain unclear. Therefore, the current study investigated the effect of KrasG12D-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) cells. Our investigation revealed that KrasG12D-LOH is associated with increased proliferation, invasion and reduced apoptosis in PDAC cells. The results also exhibited enhanced glycolytic phenotype of KrasG12D-LOH PDAC cells. Hyperactive mTOR plays a significant role in the initiation and maintenance of tumors. To investigate the correlation between KrasG12D-LOH and mTOR, the mTOR signaling pathway was detected by western blot analysis. We found that KrasG12D-LOH up-regulated Akt, AMPK, REDD1 and mTOR in PDAC cells. In summary, our results demonstrated that KrasG12D-LOH promotes oncogenic Kras-induced PDAC by regulating energy metabolism and mTOR signaling pathway. These data may provide novel therapeutic perspectives for PDAC.

Significant association between lower pulse pressure and increasing levels of a novel type of phospholipid.

The aim of this study was to analyze the association between pulse pressure and a novel type of phospholipid with solubility similar to that of lysophosphatidic acid (LPA), designated as AP, which was reported to be elevated during ischemia. In this cross-sectional study, 416 hypertensive patients and 252 controls aged between 35 and 70 years were enrolled consecutively. Fasting blood samples were extracted for assays of phospholipids and other biomarkers. Compared to controls, the hypertensive patients had higher levels of both LPA [odds ratio (OR) = 3.83] and AP (OR = 4.30). Changes in blood pressure did not affect the levels of LPA or AP. However AP, but not LPA, levels were significantly higher in patients with lower or higher pulse pressure (Pearson χ(2) = 11.239, P = 0.001). For patients whose pulse pressure was ≤60 mmHg, plasma levels of AP were significantly negatively correlated with pulse pressure. However, this was not observed for LPA and nine other biomarkers, including lipoproteins. Plasma levels of AP increased in hypertensive patients with higher or lower pulse pressure. Thus, attention should be paid to the possibility of cerebral ischemia in hypertensive patients when they have abnormal pulse pressure, especially for those with relatively low pulse pressure.

Macro- and microcirculatory effects of tetramethylpyrazine and extract of Charthamus tinctorius L. in rabbit mesentery.

Effects of tetramethylpyrazine (TMP) and that of extracts of Charthamus tinctorius L. (CTL) on the macro- and microcirculation in rabbit mesentery were studied. The intestinal arterial blood flow (Qa) was measured using an electromagnetic flowmeter, together with the arterial blood pressure (Pa). The inner diameter and red cell velocity in single arteriole in the mesentery were measured by a video-image technique and a dual-slit photometric method, respectively. Using the measured diameter and red cell velocity, the arteriolar blood flow (Qm) was calculated. Both the Qa and Qm decreased when Pa was decreased after the intravenous administration of TMP, CTL, Nicardipine, Phentolamine and acetylcholine (Ach). Changes in Qa and Qm with changes in Pa were analyzed, and it was found that (i) both the Pa-Qa and Pa-Qm curves, during the administration of TMP or CTL, show different patterns from those during the administration of Nicardipine or Phentolamine; (ii) the Pa-Qa and Pa-Qm curves after the administration of TMP or CTL show similar patterns with those after the administration of Ach.

Dopa-responsive dystonia: pathological and biochemical observations in a case.

We report the first neuropathological and neurochemical study of a patient with dopa-responsive dystonia. She had onset of foot dystonia at age 5 years and by age 8 years it was generalized with prominent right leg and arm involvement. On levodopa 750 mg daily she had complete symptomatic improvement that was sustained for 11 years until death. Pathological studies revealed normal numbers of hypopigmented substantia nigra neurons, normal tyrosine hydroxylase (TH) immunoreactivity and TH protein in the SN, no inclusion bodies or gliosis, and no evidence of a degenerative process in the striatum. Biochemical studies revealed reduced dopamine in the substantia nigra and striatum (8% in the putamen and 18% of control in the caudate) with a similar but not identical subregional distribution as in idiopathic Parkinson's disease. In the striatum, TH protein and TH activity was reduced, with the loss more pronounced in the putamen than the caudate. The GBR 12935 binding to DA transporter was normal in the caudate and at the lower end of the range of control values in the putamen. We conclude that disturbed dopamine synthetic capacity or a reduced arborization of striatal dopamine terminals may be the major disturbance in dopa-responsive dystonia.