Omega-3 polyunsaturated fatty acid inhibits the malignant progression of hepatocarcinoma by inhibiting the Wnt/ß-catenin pathway.

OBJECTIVE: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) has been found to possess anti-cancer potential in previous studies. However, the underlying mechanism of ω-3 PUFA in protecting hepatocarcinoma has not been fully elucidated. This study aims to explore the function of ω-3 PUFA in the development of hepatocarcinoma and its potential mechanism. PATIENTS AND METHODS: In this study, human hepatocarcinoma cell line Hep G2 was treated with ω-3 PUFA. Cell counting kit-8 (CCK-8) and cell cloning assay were applied to detect the proliferation of Hep G2 cells. In addition, flow cytometry was performed to analyze the cell cycle and apoptosis rate. At the same time, the effect of ω-3 PUFA on invasion and metastasis of hepatocarcinoma cells were analyzed by transwell assay. Moreover, protein levels of key factors in Wnt/ß-catenin pathway were detected by Western blot. RESULTS: Cell proliferation of Hep G2 cells was decreased after ω-3 PUFA treatment in a time- and dose-dependent manner. CCK-8 assay showed that the IC50 value was 12.8 ± 0.67 µmol/L, 8.8 ± 0.43 µmol/L and 4.6 ± 0.42 µmol/L after ω-3 PUFA treatment for 24 h, 48 h and 72 h, respectively. Besides, ratio of Hep G2 cells blocked at G2/M phase after ω-3 PUFA treatment (5 µmol/L, 10 µmol/L and 20 µmol/L) was increased in a dose-dependent manner (p<0.05). Meanwhile, ω-3 PUFA could increase cell apoptosis (p<0.05) and inhibit cell proliferation. In addition, ω-3 PUFA reduced protein expressions of total, cytoplasmic and nuclear ß-catenin in Hep G2 cells, indicating that the Wnt/ß-catenin pathway is inhibited. Decreased expression levels of Dvl-2, Dvl-3, GSK-3ß (p-ser9), c-myc and survivin, and increased expression levels of GSK-3 (p-tyr216) and Axin-2 were observed in Hep G2 cells treated with ω-3 PUFA, but no significant alteration in total GSK-3ß protein level was observed (p>0.05). CONCLUSIONS: Omega-3 PUFA regulates the malignant progression of hepatocarcinoma by inhibiting proliferation and promoting apoptosis of hepatocarcinoma cells via Wnt/ß-catenin signaling pathway.

Automaticity of subsidiary pacemakers of patients with dysfunction of the sinus node.

Automaticity (postpacing impulse recovery time) of the sinus node or subsidiary pacemakers (or both) was determined by intracardiac recordings and atrial overdrive pacing in three patients with disease of the sinus node. Their electrocardiographic manifestations included sinus bradycardia, sinoatrial block, sinus arrest, atrioventricular junctional rhythm, and atrioventricular dissociation. One patient, who initially had syncope, demonstrated prolonged time for recovery of the sinus node (maximum corrected value, 3,485 msec) and impaired atrioventricular junctional automaticity (maximum corrected junctional recovery time, 1,460 msec). Of the remaining two patients without syncopal attacks, one had an adequate low atrial or junctional escape mechanism following cessation of pacing. The maximum low atrial escape interval was 1,660 msec, and the maximum junctional recovery time was 1,770 msec (corrected value, 140 msec). The third patient disclosed a prolonged maximum corrected recovery time for the sinus node (870 msec), while the maximum junctional recovery time was only 1,810 msec (corrected value, 160 msec). We conclude that automaticity of the subsidiary pacemakers in disease of the sinus node can be determined in the presence of atrioventricular dissociation or total sinus arrest, and that determination of the recovery time of the subsidiary pacemakers may be useful in identifying symptomatic patients with sinus nodal dysfunction.

Electrophysiologic manifestations in so-called "sick sinus syndrome".

Electrophysiologic disorders in 17 patients with sick sinus syndrome (SSS) were assessed by recording of intracardiac electrograms, atrial overdrive pacing and extrastimulus technique. Significant suppression of the sinoatrial node (SAN) by overdrive pacing (maximum corrected SAN recovery time of longer than 560 msec) was noted in 14 or 16 patients studied. In nine patients, scanning with atrial extrastimuli, sinus rest was defined in all. In one patient there was a longer interpolation zone. Calculated sinoatrial conduction time (SACT) in individual patients varied considerably. The mean SACT was over 110 msec in 5 of 9 patients (56%). Sinus echo was demonstrated in 3; one manifested SAN- re-entrant tachycardia with rates of 72 to 77 beats/min. AV nodal echo was demonstrated in 3, two of them manifested AV nodal re-entrant tachycardia. Intracardiac electrograms revealed prolonged AV conduction time in 2 of 15 patients and prolonged His-Purkinje system conduction time in 2 of 17 patients studied. Two patients disclosed what we thought to be manifestation of intraatrial conduction disturbance. Both had considerable time interval between pacing impulse and atrial response. In one of them Mobitz type 1 and 2:1 intraatrial blocks were observed on atrial pacing and a possible internodal tract depolarization was also recorded. It is concluded that the electrophysiologic manifestations of patients with SSS cover a wide spectrum. The machanism of tachycardia can be due to either SAN or AV nodal re-entry.

Electrophysiologic diagnosis of patients with sinus node dysfunction: with special reference to a modified method for calculating sinoatrial conduction time.

The diagnostic value of maximum corrected sinus node recovery time (CSNRT) and sinoatrial conduction time (SACT) was assessed in 15 patients with clinical evidence of sinus node (SN) dysfunction and 16 control subjects. The SACT was calculated by a modified method using only those sinus cycles with A1-A1 intervals falling within one standard deviation of the mean. We also obtained a maximum SACT and a ratio of maximum/mean SACT. We found that the maximum/mean SACT ratio being useful for identifying patients with sinus arrest or sinoatrial block. Abnormal value of the ratio (greater than or equal to 1.85) was also more frequently observed in patients with syncope or dizzy spells than those without (55.6% vs. 33.3%). By applying mean SACT and maximum/mean SACT ratio, calculated by the modified method, together with maximum CSNRT, all patients with SN dysfunction could be completely isolated from the normal subjects.

Left ventricular performance in various heart diseases with or without heart failure:--an appraisal by quantitative one-plane cineangiocardiography.

Quantitative one-plane cineangiocardiography in right anterior oblique position for evaluation of LV performance was carried out in 62 patients with various heart diseases and in 13 subjects with normal LV. Parameters for evaluating both pump and muscle performances were derived from volume and pressure measurements. Of 31 patients with either systolic hypertension or LV myocardial diseases (coronary artery disease or idiopathic cardiomyopathy), 14 had clinical evidence of LV failure before the study. It was found that mean VCF and EF were most sensitive indicators of impaired LV performance among the various parameters. There was a close correlation between mean VCF and EF, yet discordant changes of both parameters were noted in some patients. Furthermore, wall motion abnormalities were not infrequently observed in patients with coronary artery disease or primary cardiomyopathy. Therefore, assessment of at least three ejection properties (EF, mean VCF and wall motion abnormalities) are considered to be essential for full understanding of derangement of LV function in heart disease. This is especially true of patients with coronary artery disease. LV behavior in relation to different pathological stresses or lesions, such as chronic pressure or volume load, myocardial disease and mitral stenosis, was also studied and possible cause of impaired LV myocardial function in mitral stenosis was discussed.

Ruptured congenital aneurysm of the right sinus of Valsalva into the right ventricle: with special reference to pathoanatomic and hemodynamic characteristics in symptomless cases.

Clinical features of 19 cases with congenital aneurysm of the right sinus of Valsalva rupturing into the right ventricular outflow region (Type 1) were analysed in relation to their pathoanatomic lesions and hemodynamic alterations. Sixteen cases were operated with one surgical death. All were catheterized together with ascending aortographic study. Rupture of the aneurysm in many cases was silent or symptomless and progressive heart failure was not quite common. Symptomatology of the patients did not seem to be related entirely to status of the pathoanatomical lesions or hemodynamic alterations. Time of the rupture, and inherent right ventricular characteristics, tolerating volume overload rather well, might be, in part, responsible for its better prognosis in some cases. However, all patients with ruptured aneurysm of the sinus of Valsalva should be treated surgically. Bacterial endocarditis is a serious complication leading to death.