St. John’s Wort Regulates Proliferation and Apoptosis in MCF-7 Human Breast Cancer Cells by Inhibiting AMPK/mTOR and Activating the Mitochondrial Pathway

St. John’s Wort (SJW) has been used as an estrogen agonist in the systems affected by menopause. Also, hypericin, a bioactive compound of SJW, has been used as a photosensitizer in photodynamic therapy. In the present study, we investigate the anti-proliferative and pro-apoptotic effects of SJWto demonstrate the chemo-preventive effect in human breast cancer cells. MCF-7 cellswere culturedwith DMSO or various concentrations of SJWethanol extract (SJWE). Cell viability, proliferation, apoptosis, the expression of proteins involved in cell growth and apoptosis, and caspase-3/7 activity were examined. SJWE dose-dependently suppressed cell growth and induced apoptosis ofMCF-7 cells. Mechanistically, SJWE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and decreased the expression of p-mammalian target of rapamycin (p-mTOR) and p-eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). Also, SJWE inhibited the phosphorylation of protein kinase B (Akt) and showed increases in the expression of pro-apoptotic proteins Bax and Bad with decreases in the expression of anti-apoptotic proteins including B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and p-Bcl-2-associated death promoter (p-Bad). SJWE at 50 µg/mL showed markedly enhanced caspase-7 activation. Taken together, our results provide evidence that SJWE shows anti-proliferative and pro-apoptotic effects via inhibition of AMPK/mTOR and activation of a mitochondrial pathway. Therefore, SJWE can be used as a chemo-preventive agent without photo-activation

GIST-AiTeR Speaker Diarization System for VoxCeleb Speaker Recognition Challenge (VoxSRC) 2023

This report describes the submission system by the GIST-AiTeR team for the VoxCeleb Speaker Recognition Challenge 2023 (VoxSRC-23) Track 4. Our submission system focuses on implementing diverse speaker diarization (SD) techniques, including ResNet293 and MFA-Conformer with different combinations of segment and hop length. Then, those models are combined into an ensemble model. The ResNet293 and MFA-Conformer models exhibited the diarization error rates (DERs) of 3.65% and 3.83% on VAL46, respectively. The submitted ensemble model provided a DER of 3.50% on VAL46, and consequently, it achieved a DER of 4.88% on the VoxSRC-23 test set.Comment: 2023 VoxSRC Track

Sonographic and cyst fluid cytological changes after EUS-guided pancreatic cyst ablation

Background and Aims The effect of EUS-guided pancreatic cyst ablation (PCA) on sonographic morphology and cyst fluid cytology is unknown. The aim of this study is to evaluate morphological, cytological and change in cyst fluid DNA after PCA. Methods In a prospective single center study, consecutive patients with suspected benign 10 to 50 mm pancreatic cysts underwent baseline EUS-FNA and EUS-PCA followed 2 to 3 months later by repeat EUS, cyst fluid analysis and possible repeat PCA. Surveillance imaging after ablation was performed at least annually and classified as complete (CR), partial (PR), or persistent with <5%, 5% to 25%, and 25% of the original cyst volume, respectively. Results 36 patients underwent EUS-PCA with ethanol alone (n = 8) or ethanol and paclitaxel (n = 28) and CR occurred in 19 (56%). After EUS-PCA, EUS showed an increase in wall diameter in 68%, decreased number of septations in 24%, increased debris in 24%, loss of mural nodule or novel calcification in 21%, and alteration of fluid viscosity in 48%. Follow-up cytology showed increased epithelial cellularity in 27%, loss or decreased cellular atypia in 15%, and increased or appearance of macrophages in 24% and inflammatory cells in 15%. Post-ablation DNA amount increased and quality decreased in 71% each. Between the CR and non-CR patients, there was no significant difference in frequency of sonographic or cytological features. In the CR group, mean DNA quantity was significantly increased after ablation (p=0.023) without a change in quality (p=0.136) Conclusions EUS-PCA induces morphological and cytological changes of the pancreatic cysts none of which appear to predict overall imaging-defined response to ablation

Vitamin D3 Supplementation Reduces the Symptoms of Upper Respiratory Tract Infection during Winter Training in Vitamin D-Insufficient Taekwondo Athletes: A Randomized Controlled Trial

Vitamin D insufficiency may be associated with increased risk of upper respiratory tract infection (URTI) in athletes. This study examined the effects of vitamin D3 supplementation on salivary immune functions and symptoms of URTI in vitamin D-insufficient taekwondo athletes. Twenty-five male taekwondo athletes, aged 19–22 years with vitamin D insufficiency [serum 25-hydroxyvitamin-D concentrations (25(OH)D, 31.3 ± 1.39 nmol/L)], participated in this study. They were randomized to receive 5000 IU/day of vitamin D3 (n = 13) or placebo capsule (n = 12) during 4 weeks of winter training. Blood samples were collected two times (pre- and post-tests) for analyzing serum 25(OH)D concentration while salivary samples were obtained three times (pre-, mid-, and post-tests) for secretory immunoglobulin A (SIgA) and lactoferrin analyses. The symptoms of URTI were reported daily during the intervention. Serum 25(OH)D concentration significantly increased by 255.6% in the vitamin D group, whereas in the placebo group it did not change (p \u3c 0.001). While the significant increase in SIgA was observed in both groups (p \u3c 0.001), elevated salivary lactoferrin level in response to winter training was found only in the placebo group (p = 0.011). The change in serum 25(OH)D concentration was negatively associated with total URTI symptoms (r = −0.435, p = 0.015). Vitamin D3 supplementation may be effective in reducing the symptoms of URTI during winter training in vitamin D-insufficient taekwondo athletes

Nitric oxide-dependent cytoskeletal changes and inhibition of endothelial cell migration contribute to the suppression of angiogenesis by RAD50 gene transfer

AbstractPrevious reports showed that human RAD50 (hRAD50) gene delivery induced regression of an experimental rat tumor and porcine neointimal hyperplasia. In this study, we examined the effects of hRAD50 on the morphological changes and migration of endothelial cells (EC) as possible mechanisms by which hRAD50 might block angiogenesis. Quantitative image analysis revealed significant inhibition of the number and total area of blood vessels in rat tumor tissues following hRAD50 gene delivery. hRAD50 distorted actin and tubulin arrangements, and significantly reduced the F/G-actin ratio and increased the nitric oxide (NO) production in the primary cultured human EC. These effects were blocked by pretreatment with L-NAME (NG-nitro-L-arginine-methyl ester), a NO synthase inhibitor. FACScan analysis showed that NO was involved in the necrosis and apoptosis of EC by hRAD50. hRAD50 also inhibited EC migration in an in vitro wound-healing model. These results indicate that NO-dependent cytoskeletal changes and inhibition of EC migration contribute to the suppression of angiogenesis by hRAD50 delivery in vivo

The hemodynamic effects of insulin following overdosage with levobupivacaine or racemic bupivacaine in dogs

Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has not been easy as expected. Following the recent reports that proposed the resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each group received continuous intravenous infusions of RBUP or LBUP until the mean arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2 U/kg) was administered. Both groups were successfully resuscitated. At CVC, a decrease of cardiac output and an increase of systemic vascular resistance were observed but to a lesser degree in the LBUP group (p<0.05). After insulin injection, the MAP further declined to under 40 mmHg for several minutes, which was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP in anesthetized dogs could be successfully resuscitated by insulin. Compared with RBUP, however, the less degree of vasoconstriction by LBUP and the innate vasodilatory property of insulin yielded a delayed increment of MAP during the immediate resuscitation period in the LBUP-induced CVC