Standardized flavonoid-rich fraction of Artemisia princeps Pampanini cv. Sajabal induces apoptosis via mitochondrial pathway in human cervical cancer HeLa cells

Ethnopharmacological relevance

Artemisia princeps Pampanini is widely used in Eastern traditional medicine for the treatment of circulatory disorders, such as, dysmenorrhea, hematuria, hemorrhoids, and inflammation, and is also used to treat chronic conditions, such as, cancers, ulcers, and digestive disorders.

Aim of the study

The purpose of this study is to investigate the effect of a standardized flavonoid-rich fraction of Artemisia princeps Pampanini cv. Sajabal (FRAP) on the induction of apoptosis and the molecular mechanism involved in human cervical cancer HeLa cells.

Materials and methods

Human cervical cancer HeLa cells were treated with FRAP and apoptosis was detected by cell morphologic observation, annexin-V-PI staning and western blot analysis on the expression of protein associated with cell death.

Results

FRAP led to the cleavages of caspase-3, -8, and -9 and the cleavage of poly (ADP-ribose) polymerase (PARP) in HeLa cells. Caspase-3 inhibitor (z-DEVD-fmk), caspase-8 inhibitor (z-IETD-fmk), caspase-9 inhibitor (z-LEHD), and broad caspase inhibitor (z-VAD-fmk) significantly suppressed the FRAP-induced accumulation of annexin V positive cells. Furthermore, it was found that FRAP caused a loss of mitochondrial membrane potential (MMP) and the release of cytochrome c to the cytosol. Furthermore, the overexpression of Bcl-xL significantly prevented FRAP-induced apoptosis, MMP changes, and the activations of caspase-3, -8, and -9. Interestingly, pretreatment with caspase-8 inhibitor significantly reduced the FRAP-induced activation of caspase-3 but not that of caspase-9, whereas the caspase-3 inhibitor, z-DEVD-fmk, markedly attenuated the FRAP-induced activation of caspase-8. In BALB/c^nu/nu mice bearing a HeLa xenograft, FRAP dosed at 25 or 50 mg/kg significantly inhibited tumor growth.

Conclusion

Our results indicate caspase-mediated activation of the mitochondrial death pathway plays a critical role in the FRAP-induced apoptosis of HeLa cells and that FRAP inhibits the in vivo tumor growth of HeLa xenograft mice.     

Results of conservative management for consecutive esotropia after intermittent exotropia surgery

Purpose

To examine the clinical course of consecutive esotropia (ET) using conservative management, after intermittent exotropia (IXT) surgery.

Methods

This study included 149 out of 151 consecutive patients with ET after IXT surgery, who were managed conservatively. The clinical course of consecutive ET was examined and the patients were classified into two groups based on the duration of esodeviation: (1) >3 weeks (persistent ET group, n=56) and (2) <3 weeks (transient ET group, n=93). Patient characteristics and treatment outcomes, including the recurrence of exotropia and stereopsis, were compared between the two groups.

Results

All patients with ET were managed with full-time alternate occlusion and/or with a Fresnel prism. In 149 patients out of 151 consecutive patients, 82% of ET disappeared at 12-month follow-up and all at the last follow-up visit (31.4±23.5 months). At the final visit, a recurrence of exotropia of >10 prism dioptres was significantly less frequent in the persistent ET group than in the transient ET group (25% vs 62%, respectively; P=0.01). However, stereopsis outcome was not significantly different between the two groups, and stereopsis change was not affected by age.

Conclusions

By using conservative management only, persistent consecutive ET after IXT surgery disappeared in most cases by the 1-year follow-up visit after surgery. Recurrence of exotropia was significantly less frequent in patients with persistent ET, yet the sensory outcome was not affected by the duration of consecutive ET or age.     

Associations of the infancy body mass index peak with anthropometry and cardiometabolic risk in Mexican adolescents

Background: Early-life growth dynamics are associated with future health. Little is known regarding timing and magnitude of the infancy body mass index (BMI) peak with adiposity and metabolic biomarkers during adolescence.

Aim: To examine associations of the infancy BMI peak with anthropometry and cardiometabolic risk during peripuberty.

Methods: Among 163 ELEMENT participants, this study estimated age and magnitude of the infancy BMI peak from eight anthropometric measurements from birth–36?months using Newton’s Growth Models, an acceleration-based process model. Associations were examined of the infancy milestones with anthropometry and cardiometabolic risk at 8–14?years using linear regression models that accounted for maternal calcium supplementation and age; child’s birthweight, sex, and age; and the other infancy milestone.

Results: Median age at the infancy BMI peak was 9.6?months, and median peak BMI was 16.5?kg/m². Later age and larger magnitude of the peak predicted higher BMI z-score, waist circumference, and skinfold thicknesses; i.e. each 1?month of age at peak and each 1?kg/m² of peak BMI corresponded with 0.04 (0.01–0.07) and 0.33 (0.17–0.48) units of higher BMI z-score, respectively. Later age at peak was also a determinant of worse glycaemia and higher blood pressure.

Conclusion: Later age and larger magnitude of the infancy BMI peak are associated with higher adiposity at 8–14?years of age. Later age but not magnitude of the BMI peak are related to a worse cardiometabolic profile during peripuberty.     

Treatment of Post-Ablation Bronchopleural Fistula Using Percutaneous Synthetic Hydrogel Surgical Sealant: Initial Experience of Safety and Efficacy

CardioVascular and Interventional Radiology - Purpose Bronchopleural fistula is a rare but serious complication of lung ablation, as it is difficult to treat and is associated with a high mortality...