Salvia miltiorrhiza Bunge Ameliorates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress via Nrf-2/ HO-1 Activation.

Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative effects of Salvia miltiorrhiza Bunge extract (HLT-101) on BPH through the regulation of oxidative stress and inflammation. A testosterone propionate (TP)-induced BPH rat model was orally administered HLT-101 (20, 40, or 80 mg/kg), and its effects on oxidative stress- and inflammation-related gene expression were examined. Further, HLT-101 was assessed for its effect on reactive oxygen species (ROS) levels and Nrf-2/HO-1 signaling pathways in BPH-1 cells. HLT-101 decreased testosterone-induced excessive free radical production and inflammatory factor activation. Moreover, HLT-101 treatment significantly decreased the intracellular ROS level in the TNF-α and IFN-γ treated BPH-1 cells through the activation of Nrf-2. In addition, HLT-101 treatment inhibited the NF-κB pathway and androgen receptor (AR) signaling, which is highly linked to the pathogenesis of BPH. Therefore, HLT-101 has the potential to be an effective treatment reagent for BPH because of its ability to reduce inflammation and oxidative stress via Nrf-2/HO-1 signaling.

Radiological Outcomes of Unilateral Laminotomy for Bilateral Decompression in Lumbar Spinal Stenosis With and Without Discectomy.

BACKGROUND: Unilateral laminotomy for bilateral decompression (ULBD) is a minimally invasive surgical technique widely used in patients with lumbar spinal stenosis and low-grade spondylolisthesis. However, few studies have investigated the long-term effects of the unilateral approach of ULBD on postoperative coronal imbalance, and the effect of additional discectomy on ULBD has not yet been evaluated in detail. METHODS: Sixty-one patients with lumbar spinal stenosis who underwent ULBD with or without discectomy were identified. The ULBD with discectomy group included 27 patients, and the ULBD without discectomy group included 34 patients. We analyzed the changes in various radiographic parameters, such as global lordosis (GL), segmental lordosis (SL), global coronal angle (GCA), segmental coronal angle (SCA), disc height (DH), global range of motion (GROM), and segmental range of motion (SROM) following the surgery and compared these parameters between the two groups. RESULTS: In patients who underwent ULBD with discectomy, segmental coronal angle (SCA) significantly decreased from 0.42 ± 4.41 (°±SD) preoperatively to -0.31 ± 4.87 postoperatively (P = 0.026), while disc height (DH) decreased from 8.80 ± 2.49 (mm ± SD) to 7.32 ± 2.60 (P < 0.001). These findings suggest a reduction in convexity as disc height decreased on the laminotomy side. However, the absolute SCA value tended to approach 0° postoperatively regardless of discectomy, indicating that the preoperative scoliosis has improved. In both groups, the lordotic angles and range of motion (ROM) parameters showed no changes before and after surgery. CONCLUSIONS: ULBD preserved lumbar lordosis and motion with or without discectomy during the 2-year follow-up period. Improvement in coronal balance was observed after ULBD regardless of discectomy, without significant negative effects on sagittal and coronal spine stability.

DJ-1 null dopaminergic neuronal cells exhibit defects in mitochondrial function and structure: involvement of mitochondrial complex I assembly.

DJ-1 is a Parkinson's disease-associated gene whose protein product has a protective role in cellular homeostasis by removing cytosolic reactive oxygen species and maintaining mitochondrial function. However, it is not clear how DJ-1 regulates mitochondrial function and why mitochondrial dysfunction is induced by DJ-1 deficiency. In a previous study we showed that DJ-1 null dopaminergic neuronal cells exhibit defective mitochondrial respiratory chain complex I activity. In the present article we investigated the role of DJ-1 in complex I formation by using blue native-polyacrylamide gel electrophoresis and 2-dimensional gel analysis to assess native complex status. On the basis of these experiments, we concluded that DJ-1 null cells have a defect in the assembly of complex I. Concomitant with abnormal complex I formation, DJ-1 null cells show defective supercomplex formation. It is known that aberrant formation of the supercomplex impairs the flow of electrons through the channels between respiratory chain complexes, resulting in mitochondrial dysfunction. We took two approaches to study these mitochondrial defects. The first approach assessed the structural defect by using both confocal microscopy with MitoTracker staining and electron microscopy. The second approach assessed the functional defect by measuring ATP production, O(2) consumption, and mitochondrial membrane potential. Finally, we showed that the assembly defect as well as the structural and functional abnormalities in DJ-1 null cells could be reversed by adenovirus-mediated overexpression of DJ-1, demonstrating the specificity of DJ-1 on these mitochondrial properties. These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease.

DJ-1 mediates paraquat-induced dopaminergic neuronal cell death.

There are two causes of Parkinson's disease (PD): environmental insults and genetic mutations of PD-associated genes. Environmental insults and genetic mutations lead to mitochondrial dysfunction, and a combination of mitochondrial dysfunction and increased oxidative stress in dopaminergic neurons is thought to contribute to the pathogenesis of PD. Among the PD-associated genes, DJ-1 acts as a redox sensor for oxidative stress and has been also proposed to maintain mitochondrial complex I activity. To understand molecular functions of DJ-1 in the cell, we have generated DJ-1 null cells from the DJ-1(-/-) mouse embryos. Using these null cells, we investigated the susceptibility to an environmental toxin, paraquat, which is known to inhibit mitochondrial complex I. Interestingly, we found that DJ-1 null cells showed a resistance to paraquat-induced apoptosis, including reduced poly (ADP-ribose) polymerase and procaspase-3. Also DJ-1 null cells generated less superoxide than SN4741 cells by paraquat treatment. Consistent with the reduced paraquat sensitivity, DJ-1 null cells showed reduced complex I activity, which was partially rescued by ectopic DJ-I expression. In summary, our results suggest that DJ-1 is critical to maintain mitochondrial complex I and complex I could be a key target in interaction of paraquat toxicity and DJ-1 for giving rise to PD.