Oxidative stress in peroxisomes induced by androgen receptor inhibition through peroxisome proliferator-activated receptor promotes enzalutamide resistance in prostate cancer.

Androgen receptor (AR)-targeting therapy induces oxidative stress in prostate cancer. However, the mechanism of oxidative stress induction by AR-targeting therapy remains unclear. This study investigated the mechanism of oxidative stress induction by AR-targeting therapy, with the aim to develop novel therapeutics targeting oxidative stress induced by AR-targeting therapy. Intracellular reactive oxygen species (ROS) was examined by fluorescence microscopy and flow cytometry analysis. The effects of silencing gene expression and small molecule inhibitors on gene expression and cytotoxic effects were examined by quantitative real-time PCR and cell proliferation assay. ROS induced by androgen depletion co-localized with peroxisomes in prostate cancer cells. Among peroxisome-related genes, PPARA was commonly induced by AR inhibition and involved in ROS production via PKC signaling. Inhibition of PPARα by specific siRNA and a small molecule inhibitor suppressed cell proliferation and increased cellular sensitivity to the antiandrogen enzalutamide in prostate cancer cells. This study revealed a novel pathway by which AR inhibition induced intracellular ROS mainly in peroxisomes through PPARα activation in prostate cancer. This pathway is a promising target for the development of novel therapeutics for prostate cancer in combination with AR-targeting therapy such as antiandrogen enzalutamide.

Scaffold-free bone-like 3D structure established through osteogenic differentiation from human gingiva-derived stem cells.

Introduction & objectives: Stem cell therapy for regenerative medicine has been sincerely investigated, but not still popular although some clinical trials show hopeful results. This therapy is suggested to be a representative candidate such as bone defect due to the accident, iatrogenic resection oncological tumor, congenital disease, and severe periodontitis in oral region. Recently, the Bio-3D printer "Regenova®" has been introduced as an innovative three-dimensional culture system, equipped scaffold-free bio-assembling techniques without any biomaterials. Therefore, we expected a mount of bone defect could be repaired by the structure established from this Bio-3D printer using osteogenic potential stem cells. Material & methods: The gingival tissue (1x1 mm) was removed from the distal part of the lower wisdom tooth of the patients who agreed our study. Human Gingival Mesenchymal Stem Cells (hGMSCs) were isolated from this tissue and cultured, since we confirmed the characteristics such as facile isolation and accelerated proliferation, further, strong potential of osteogenic-differentiation. Spheroids were formed using hGMSC in 96-well plates designed for low cell adhesion. The size of the spheroids was measured, and fluorescent immunostaining was employed to verify the expression of stem cell and apoptosis marker, and extracellular matrix. Following four weeks of bone differentiation, µCT imaging was performed. Calcification was confirmed by alizarin red and von Kossa staining. Fluorescent immunostaining was utilized to assess the expression of markers indicative of advanced bone differentiation. Results: We have established and confirmed the spheroids (∼600 µm in diameter) constructed from human GMSCs (hGMSCs) still maintain stem cell potentials and osteogenic differentiation abilities from the results that CD73 and not CD34 were expressed as stem cell positive and negative marker, respectively. These spheroids were pilled up like cylindal shape to the "Kenzan" platform of Bio-3D printer and cultured for 7days. The cylindal structure originated from compound spheroids were tried to differentiate into bone four weeks with osteogenic induction medium. The calcification of bio-3D printed bone-like structures was confirmed by alizarin red and Von Kossa staining. In addition, µCT analysis revealed that the HU (Hounsfield Unit) of the calcified structures was almost identical to that of trabecular bone. Immunofluorescent staining detected osteocalcin expression, a late-stage bone differentiation marker. Conclusion: For the first time, we have achieved the construction of a scaffold-free, bone-like luminal structure through the assembly of spheroids comprised of this hGMSCs. This success is sure to be close to the induction of clinical application against regenerative medicine especially for bone defect disease.

A prospective, single-center, randomized clinical trial to evaluate the efficacy of three types of laser vaporization surgeries using a 180-W GreenLight XPS laser, a 300-W diode laser, and a 200-W thulium laser for the treatment of benign prostatic hyperplasia.

OBJECTIVES: This study aimed to compare the safety and efficacy of three different laser prostate vaporization surgeries, which were photoselective vaporization of the prostate (PVP), diode laser vaporization (DVP), and thulium laser vaporization (ThuVAP), for the treatment of benign prostatic hyperplasia (BPH) in a randomized clinical trial. METHODS: A total of 71 consecutive patients with BPH were included; 23 patients were treated with PVP, 23 with DVP, and 25 with ThuVAP. Patients were evaluated with disease-related symptomatic questionnaires, Quality of Life (QOL) Index, and maximum urinary flow rate (Qmax ) for 12 months. Patients were monitored to record operation/vaporization time, 24-hour hemoglobin/sodium drop, length of catheterization/hospitalization, and perioperative/postoperative complications. RESULTS: In all three groups, patients showed significant and comparable improvements in symptom scores, QOL Index, and Qmax during the 12-month follow-up period. The mean operation/vaporization time was equivalent across all three groups at 69/23 (PVP), 81/34 (DVP), and 76/32 minutes (ThuVAP), while the applied laser energy was lower for PVP at 157 kJ compared to the other two techniques (DVP at 358 kJ, ThuVAP at 240 kJ). The mean vaporization rates per unit energy were significantly different between the three groups (PVP 0.16, DVP 0.09, and ThuVAP 0.09 mL/kJ). There were no significant differences in the main safety profiles between the three groups. CONCLUSIONS: Our study demonstrated that these three types of laser surgeries are similar in terms of complications and outcomes, with excellent hemostasis and high patient satisfaction. It was suggested that sufficient tissue vaporization could be achieved using less energy through PVP surgery.

Superconducting-Gap Anisotropy of Iron Pnictides Investigated via Combinatorial Microwave Measurements.

One of the most significant issues for superconductivity is clarifying the momentum-dependent superconducting gap Δ([Formula: see text]), which is closely related to the pairing mechanism. To elucidate the gap structure, it is essential to investigate Δ([Formula: see text]) in as many different physical quantities as possible and to crosscheck the results obtained in different methods with each other. In this paper, we report a combinatorial investigation of the superfluid density and the flux-flow resistivity of iron-pnictide superconductors; LiFeAs and BaFe2(As1-xPx)2 (x = 0.3, 0.45). We evaluated Δ([Formula: see text]) by fitting these two-independent quantities with a two-band model simultaneously. The obtained Δ([Formula: see text]) are consistent with the results observed in angle-resolved photoemission spectroscopy (ARPES) and scanning-tunneling spectroscopy (STS) studies. We believe our approach is a powerful method for investigating Δ([Formula: see text]) because it does not require a sample with clean surface unlike ARPES and STS experiments, or a rotational magnetic-field system for direct measurements of the angular dependence of thermodynamic quantities.