Chemoresistance in gastric cancer is attributed to the overexpression of excision repair cross-complementing 1 (ERCC1) caused by microRNA-122 dysregulation.

MicroRNAs are deemed as key regulators of gene expression. In particular, the elevated expression of excision repair cross-complementing 1 (ERCC1) significantly reduced the effectiveness of gastric cancer treatment by cisplatin (CDDP)-based therapies. In this paper, qRT-PCR and western blot were adopted to measure miR-122 and ERCC1 messenger RNA (mRNA) expression in all samples. Luciferase assay was carried out to verify the role of ERCC1 as a target of miR-122. The CCK-8 assay was carried out to study the effect of ERCC1 and miR-122 on cell survival and apoptosis. The results demonstrated that miR-122 expression was reduced in cisplatin-resistant gastric cancer. Using bioinformatic analysis, miR-122 was shown to target the 3'-UTR of human ERCC1. A dual-luciferase assay demonstrated that miR-122 downregulated ERCC1 expression, while the mutations in ERCC1 3'-UTR abolished its interaction with miR-122. Transfection of miR-122 mimics decreased the levels of ERCC1 mRNA and protein expression, while the transfection of miR-122 inhibitors increased the levels of both ERCC1 mRNA and protein expression. Furthermore, we found that overexpressed miR-122 promoted the proliferation of MKN74 cells and reduced their apoptotic by targeting ERCC1. In addition, the levels of miR-122 and ERCC1 were negatively correlated in gastric cancer samples. In summary, the reduced miR-122 expression may play an essential role in the induction of cisplatin-resistance by increasing ERCC1 expression.

[Differences of blood plasma renin activity, angiotensin II and aldosterone levels in essential or secondary hypertension].

OBJECTIVE: To study on the difference of plasma renin activity (PRA), angiotensin II (Ang II), and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO), and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR). METHODS: The plasma aldosterone, Ang II and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA, n = 111), aldosterone-producing adenoma (APA, n = 118), PHEO (n = 98) and EH (n = 86). ARR was calculated. RESULTS: Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [374 (294, 465) pmol/L and 629 (449, 997) pmol/L] and PA group [471 (346, 632) pmol/L and 673 (499, 825) pmol/L] were higher than those in EH group [277 (224, 332) pmol/L and 427 (341, 501) pmol/L] (P < 0.01). They were also higher in APA group [576 (416, 731) pmol/L and 726 (554, 906) pmol/L] than those in IHA group [399 (313, 504) pmol/L and 609 (485, 776) pmol/L] (P < 0.01). Ang II levels in both positions were lower in PA group [43.2 (26.4, 74.4) ng/L and 60.1 (38.5, 103.6) ng/L] than in EH group [56.7 (43.3, 78.9) ng/L and 84.3 (61.3, 108.4) ng/L] or PHEO group [54.3 (29.9, 101.5) ng/L and 102.8 (49.9, 167.0) ng/L] (all P values < 0.01), and there was no difference between IHA and APA group (P > 0.05). The PRA level in both positions of each group were PHEO group [0.3 (0.2, 1.0) µg · L(-1) · h(-1) and 1.4 (0.6, 3.4) µg · L(-1) · h(-1)] > EH group [0.2 (0.1, 0.4) µg · L(-1) · h(-1) and 0.6 (0.4, 1.0) µg · L(-1) · h(-1)] (P < 0.01) > PA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (P < 0.01), and APA group [0.1 (0.1, 0.1) µg · L(-1) · h(-1) and 0.1 (0.1, 0.3) µg · L(-1) · h(-1)] < IHA group [0.1 (0.1, 0.2) µg · L(-1) · h(-1) and 0.2 (0.1, 0.3) µg · L(-1) · h(-1)] (supine P < 0.01; upright P < 0.05). APA was divided into 2 types with renin-Ang II-responsive APA (n = 26) and unresponsive APA (n = 92). The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang II-responsive APA than in unresponsive APA patients. ARR in upright was higher in PA group (P < 0.01) but lower in PHEO group (P < 0.05) compared with EH. ARR was higher in APA than in IHA (P < 0.01). The sensitivity and specificity of ARR as 40 (aldosterone unit: ng/dl; PRA unit: µg · L(-1) · h(-1); its value should multiply 27.7 when transferred to pmol/L, simili) were 93% and 76%, respectively. CONCLUSION: The levels of PRA, Ang II and aldosterone from patients with EH, PA and PHEO are significant different. ARR as 40 in upright position could be used for PA screening cutoff point.

[An analysis of hyperinsulinemia in Bartter syndrome].

OBJECTIVE: To analyse hyperinsulinemia in Bartter syndrome. METHODS: Twenty-three cases of Bartter syndrome [age (27 ± 9) years; fasting serum potassium (2.8 ± 0.5) mmol/L], 20 patients of aldosterone-producing adenoma [APA, age (45 ± 11)years, fasting serum potassium (3.0 ± 0.4) mmol/L], 20 patients of idiopathic hyperaldosteronism [IHA, age (51 ± 11) years, fasting serum potassium (3.4 ± 0.2) mmol/L] were diagnosed in Peking Union Medical College Hospital from September 2003 to May 2008. All patients underwent 3-hours oral glucose tolerance test (3hOGTT), postural stimulation test and calculated HOMA-insulin resistance (HOMA-IR) and HOMA-insulin sensitivity (HOMA-IS) by Homeostasis model. RESULTS: The insulin area under curve[(229.0 ± 162.4) mIU×L(-1)×h] was significantly higher than APA group [(121.2 ± 81.1) mIU×L(-1)×h, P < 0.05] and were similar to the aged-matched patients with IHA [(227.7 ± 158.6) mIU×L(-1)×h]. But HOMA-IR in Bartter group were similar to APA group (1.96 ± 1.14 vs 1.41 ± 0.91), and HOMA-IR in APA group was lower than IHA group (1.96 ± 1.14 vs 2.40 ± 1.60, P < 0.05). There was no deference in HOMA-IS among three groups, but APA group had lower level. In all three groups, the peak of insulin secretion was delayed. CONCLUSION: Bartter syndrome patients commonly present with hyperinsulinemia.

[Relationship between plasma level of leptin and the expression of leptin receptor in human adrenal tissues and tumors].

OBJECTIVE: To compare the mRNA, protein expression of long leptin receptor (Ob-Rb) in human adrenal tissues and tumors and observe the plasma level of leptin in primary aldosteronism (PA), cortisol-secreting tumors (CS) and pheochromocytomas (PHEO). METHODS: Total RNA and protein were extracted from 6 normal human adrenal glands, 10 CS, 20 PHEO; and 14 aldosterone-producing adenomas (APA) (RNA), 10 APA (protein); plasma samples were drawn from 20 controls, 15 PHEO, 29 PA and 11 CS. RESULTS: The mRNA and protein of Ob-Rb were widely expressed in human adrenal glands and tumors. The mRNA (0.32±0.12) and protein (1.31±0.26) expressions of Ob-Rb were higher in normal human adrenal cortex (C) than all other tissues (P<0.05) while the mRNA expression of Ob-Rb in APA (0.15±0.10) was higher than CS (0.05±0.02) (P<0.05). The mRNA expression of Ob-Rb in APA was positively correlated with plasma supine aldosterone level (r=0.670, P=0.024). The mRNA expression of Ob-Rb in CS was positively correlated with 24-hour urinary free cortisol level (r=0.870, P=0.005). The plasma level of leptin was higher in CS than in non-CS groups (P=0.001). CONCLUSIONS: Ob-Rb is widely expressed in adrenal tissues and tumors. There is a differential expression in various tissues. Further studies are warranted to understand the relationship between leptin and adrenal gland.

[Circulating leptin and ghrelin in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the potential roles of leptin and ghrelin in malnutrition in patients with chronic obstructive pulmonary disease (COPD). METHODS: Plasma leptin, total ghrelin and active ghrelin, TNF-alpha and IL-6 levels were determined in 53 patients with COPD and 26 control subjects. Body compositions were assessed by bioelectrical impedance analysis. RESULTS: Plasma leptin levels were significantly lower in underweight patients than those in normal weight patients and in healthy controls [2.6 (2.0 - 4.4) vs. 6.1 (5.1 - 7.8) vs. 4.8 (3.3 - 6.1) ng/L]. The leptin level was associated positively with fat mass (r = 0.662, P = 0.000) and TNF-alpha (r = 0.431, P = 0.001) in the patients. By a stepwise multiple regression analysis, fat mass, TNF-alpha, presence of COPD, smoking and sex were found to affect leptin level (R(2) = 0.635). Both plasma total ghrelin levels and active ghrelin levels were significantly higher in underweight patients than those in normal weight patients and in healthy controls [total ghrelin: 1090 (860 - 2838) vs. 765 (651 - 941) vs. 844 (676 - 1045) ng/L; active ghrelin: 63 (50 - 97) vs. 47 (41 - 56) vs. 54 (41 - 60) ng/L]. Plasma total ghrelin and active ghrelin were associated negatively with BMI respectively (total ghrelin: r = -0.517, P = 0.000; active ghrelin: r = -0.417, P = 0.002). CONCLUSIONS: Plasma leptin levels were decreased, while plasma total ghrelin and active ghrelin levels were elevated in underweight patients with COPD, and the levels were associated with nutritional parameters. The plasma levels of leptin and ghrelin may be a compensatory mechanism in malnutritional status of COPD. After adjustment for nutritional parameters, leptin levels were elevated in COPD patients and correlated to TNF-alpha. The result suggests that leptin may play a role in systemic inflammation of COPD.

[Effect of hypokalemia on glucose metabolism in primary hyperaldosteronism].

OBJECTIVE: To investigate the effect of potassium deficiency on glucose and insulin metabolism in primary hyperaldosteronism, including aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). METHODS: Totally 178 patients who were diagnosed as primary hyperaldosteronism (103 patients with APA and 75 with IHA) were divided into hypokalemia group and normal potassium group according to their serum potassium levels. All patients received 3 hours of oral glucose tolerance test and aldosterone test to observe the relationship among glucose, insulin and serum potassium. RESULTS: Area under curve of serum potassium, area under curve of plasma insulin, and fasting serum insulin were significantly lower in the hypokalemia group than in the normal potassium group (P <0. 05, P <0. 01); area under curve of glucose and aldosterone level were significantly higher in the hypokalemia group than in the normal potassium group ( P < 0. 05 ) . The prevalence of metabolic syndrome was significantly higher in IHA than in APA (57. 3% vs 38. 8% ; P < 0. 05). CONCLUSION: Hypokalemia may play an important role in inhibiting insulin secretion in primary hyperaldosteronism.