A small H2O-soluble ingredient of royal jelly lower cholesterol levels in liver cells by suppressing squalene epoxidase.

Excessive cholesterol in the liver is harmful for our health and may cause many diseases, such as fatty liver disease. Many studies in human and animal models have reported that royal jelly (RJ) can be used to treat atherosclerosis. However, the real mechanisms behind this action is unclear. In this study, we investigated the efficacy of RJ on gene expression of squalene epoxidase (SE) a major enzyme involved in cholesterol biosynthesis in HepG2 cells. We found that the expression of SE was decreased in response to RJ treatment. We also found that the origin of the RJ affected its strength. To find out the active fraction of RJ in cholesterol suppression, we separated RJ into two parts based on the molecular weights using ultrafiltration membrane. We found that the fraction <10kDa from RJ had comparable effect on SE expression, especially its water-soluble part. Taken together, we think RJ suppresses cholesterol by decreasing SE gene expression in liver. The active fraction of RJ in this action is <10kDa in water-soluble form.

Postprandial proximal gastric acid pocket and its association with gastroesophageal acid reflux in patients with short-segment Barrett's esophagus.

OBJECTIVE: To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett's esophagus (BE). METHODS: Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out. RESULTS: The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH. CONCLUSIONS: In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.

Potential rat model of anxiety-like gastric hypersensitivity induced by sequential stress.

AIM: To establish a rat model of anxiety-like gastric hypersensitivity (GHS) of functional dyspepsia (FD) induced by novel sequential stress. METHODS: Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood (8 wk) at which point the anxiety-like behaviors and visceromotor responses to gastric distention (20-100 mmHg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1A receptor (5-HT1AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined. RESULTS: Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequential-stress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT (51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA (2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF (304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1 (1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT (47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF (257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it (1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT (41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF (226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site (1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC (Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB (0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01) (n = 8 in each group). CONCLUSION: Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.

Reflux characteristics of 113 GERD patients with abnormal 24-h multichannel intraluminal impedance-pH tests.

OBJECTIVE: To analyze reflux parameters by means of combined multichannel intraluminal impedance and pH (MII-pH) monitoring in patients with gastroesophageal reflux disease (GERD) symptoms off medication, and to find the reflux characteristics of Chinese GERD patients and the influences of gender, age, body posture, and body mass index (BMI) on gastroesophageal reflux (GER). METHODS: Between Dec. 2008 and May 2014, 125 patients with typical GERD symptoms were subjected to 24-h MII-pH monitoring. Twelve patients with normal MII-pH profiles were not considered for analysis. The reflux parameters of 113 GERD patients with abnormal MII-pH results were analyzed. RESULTS: (1) DeMeester scores were above the normal range in 46.90% (53/113) of GERD patients. Weakly acidic refluxes were prevalent in GERD patients, and the frequency of abnormal weakly acidic reflux was 75.22% (85/113). The frequencies of abnormal symptom index (SI) and symptom association probability (SAP) were 19.47% (22/113) and 14.16% (16/113), respectively. (2) The frequencies of DeMeester scores, the %time at pH<4, and the numbers of reflux episodes and of long reflux episodes >5 min were significantly higher in male patients than in female patients. (3) The %time at pH<4 was much higher during upright periods than during supine periods. During supine periods, 31.86% (36/113) of GERD patients had delayed bolus clearance time, compared with 19.47% (22/113) during upright periods. (4) The number of abnormal DeMeester scores, %time at pH<4, and the number of acid refluxes during upright periods were significantly higher in obese GERD patients than in GERD patients with a normal BMI. Overweight GERD patients also had many more acid refluxes during upright periods than GERD patients with a normal BMI. CONCLUSIONS: Weakly acidic refluxes were prevalent in Chinese GERD patients. The factors male, gender, upright position, obesity (BMI≥25), but not age, may increase the frequency and severity of GER.