Progesterone Increases Apoptosis and Inversely Decreases Autophagy in Human Hepatoma HA22T/VGH Cells Treated with Epirubicin

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. Epirubicin can induce intracellular reactive oxygen species and is widely used to treat unresectable HCC. Progesterone has been found to inhibit the proliferation of hepatoma cells. This study was designed to test the combined effects of epirubicin and progesterone on human hepatoma cell line, HA22T/VGH. These cells were treated with different concentrations of epirubicin with or without the coaddition of 30 μM progesterone and then analyzed for apoptosis, autophagy, and expressions of apoptotic-related proteins and multidrug-resistant gene. Epirubicin treatment dose-dependently inhibited the growth of HA22T/VGH cells. Addition of 30 μM progesterone, which was inactive alone, augmented the effect of epirubicin on the inhibition of growth of HA22T/VGH cells. Cotreatment with progesterone enhanced epirubicin-induced apoptosis, as evidenced by greater increase in caspase-3 activity and in the ratio of the apoptosis-regulating protein, Bax/Bcl-XL. The combination also caused a decrease in autophagy and in the expression of multidrug resistance-related protein 1 mRNA compared to epirubicin alone. This study shows the epirubicin/progesterone combination was more effective in increasing apoptosis and inversely decreasing autophagy on HA22T/VGH cells treated with epirubicin alone, suggesting that this combination can potentially be used to treat HCC

A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation

Background: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy strongly associated with Epstein-Barr virus (EBV). AT13387 is a novel heat shock protein 90 (Hsp90) inhibitor, which inhibits the chaperone function of Hsp90 and reduces expression of Hsp90-dependent client oncoproteins. This study aimed to evaluate both the in vitro and in vivo antitumor effects of AT13387 in the EBV-positive NPC cell line C666-1.Results: Our results showed that AT13387 inhibited C666-1 cell growth and induced cellular senescence with the downregulation of multiple Hsp90 client oncoproteins EGFR, AKT, CDK4, and restored the protein expression of negative cell cycle regulator p27. We also studied the ability of AT13387 to restore p27 expression by downregulation of AKT and the p27 ubiquitin mediator, Skp2, using AKT inhibitor and Skp2 siRNA. In the functional study, AT13387 inhibited cell migration with downregulation of a cell migration regulator, HDAC6, and increased the acetylation and stabilization of α-tubulin. We also examined the effect of AT13387 on putative cancer stem cells (CSC) by 3-D tumor sphere formation assay. AT13387 effectively reduced both the number and size of C666-1 tumor spheres with decreased expression of NPC CSC-like markers CD44 and SOX2. In the in vivo study, AT13387 significantly suppressed tumor formation in C666-1 NPC xenografts.Conclusion: AT13387 suppressed cell growth, cell migration, tumor sphere formation and induced cellular senescence on EBV-positive NPC cell line C666-1. Also, the antitumor effect of AT13387 was demonstrated in an in vivo model. This study provided experimental evidence for the preclinical value of using AT13387 as an effective antitumor agent in treatment of NPC. © 2013 Chan et al.; licensee BioMed Central Ltd.published_or_final_versio

The effects of pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: protocol for a randomised controlled trial

BACKGROUND: Non-cystic fibrosis bronchiectasis is characterised by sputum production, exercise limitation and recurrent infections. Although pulmonary rehabilitation is advocated for this patient group, its effects are unclear. The aims of this study are to determine the short and long term effects of pulmonary rehabilitation on exercise capacity, cough, quality of life and the incidence of acute pulmonary exacerbations. METHODS/DESIGN: This randomised controlled trial aims to recruit 64 patients with bronchiectasis from three tertiary institutions. Participants will be randomly allocated to the intervention group (supervised, twice weekly exercise training with regular review of airway clearance therapy) or a control group (twice weekly telephone support). Measurements will be taken at baseline, immediately following the intervention and at six and 12 months following the intervention period by a blinded assessor. Exercise capacity will be measured using the incremental shuttle walk test and the six-minute walk test. Quality of life and health status will be measured using the Chronic Respiratory Questionnaire, Leicester Cough Questionnaire, Assessment of Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. The rate of hospitalisation will be captured as well as the incidence of acute pulmonary exacerbations using a daily symptom diary. DISCUSSION: Results from this study will help to determine the efficacy of supervised twice-weekly pulmonary rehabilitation upon exercise capacity and quality of life in patients with bronchiectasis and will contribute to clinical practice guidelines for physiotherapists in the management of this population. TRIAL REGISTRATION: This study protocol is registered with ClinicalTrials.gov (NCT00885521)

Risk of thyroid dysfunction associated with mRNA and inactivated COVID-19 vaccines: a population-based study of 2.3 million vaccine recipients

Background: In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset. / Methods: We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves’ disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression. / Results: A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670–1.114; CoronaVac: IRR 0.707, 95% CI 0.549–0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716–1.159; CoronaVac: IRR 0.778, 95% CI 0.618–0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744–1.023; CoronaVac: IRR 0.830, 95% CI 0.713–0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838–1.199; CoronaVac: IRR 0.963, 95% CI 0.807–1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770–1.227; CoronaVac: IRR 0.879, 95%CI 0.693–1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833–1.246; CoronaVac: IRR 0.768, 95% CI 0.613–0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899–1.201; CoronaVac: IRR 0.911, 95% CI 0.786–1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794–1.102; CoronaVac: IRR 0.945, 95% CI 0.799–1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines. / Conclusions: Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac

Strange Quark Contributions to Parity-Violating Asymmetries in the Backward Angle G0 Electron Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton and quasi-elastic electron-deuteron scattering at Q^2 = 0.22 and 0.63 GeV^2. They are sensitive to strange quark contributions to currents in the nucleon, and to the nucleon axial current. The results indicate strange quark contributions of < 10% of the charge and magnetic nucleon form factors at these four-momentum transfers. We also present the first measurement of anapole moment effects in the axial current at these four-momentum transfers.Comment: 5 pages, 2 figures, changed references, typo, and conten

Rationalisation and Validation of an Acrylamide-Free Procedure in Three-Dimensional Histological Imaging

201810_a bcmapublished_fina

Transverse Beam Spin Asymmetries at Backward Angles in Elastic Electron-Proton and Quasi-elastic Electron-Deuteron Scattering

We have measured the beam-normal single-spin asymmetries in elastic scattering of transversely polarized electrons from the proton, and performed the first measurement in quasi-elastic scattering on the deuteron, at backward angles (lab scattering angle of 108 degrees) for Q2 = 0.22 GeV^2/c^2 and 0.63 GeV^2/c^2 at beam energies of 362 MeV and 687 MeV, respectively. The asymmetry arises due to the imaginary part of the interference of the two-photon exchange amplitude with that of single photon exchange. Results for the proton are consistent with a model calculation which includes inelastic intermediate hadronic (piN) states. An estimate of the beam-normal single-spin asymmetry for the scattering from the neutron is made using a quasi-static deuterium approximation, and is also in agreement with theory

Transverse Beam Spin Asymmetries in Forward-Angle Elastic Electron-Proton Scattering

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely-polarized 3 GeV electrons from unpolarized protons at Q^2 = 0.15, 0.25 (GeV/c)^2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state, and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A_n provides a direct probe of the imaginary component of the 2-gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.Comment: 5 pages, 3 figures, submitted to Physical Review Letters; shortened to meet PRL length limit, clarified some text after referee's comment

Strange Quark Contributions to Parity-Violating Asymmetries in the Forward G0 Electron-Proton Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < Q^2 < 1.0 GeV^2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange quark contributions to the currents of the proton. The measurements were made at JLab using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate non-zero, Q^2 dependent, strange quark contributions and provide new information beyond that obtained in previous experiments.Comment: 5 pages, 2 figure