Daidzein Inhibits Human Platelet Activation by Downregulating Thromboxane A2 Production and Granule Release, Regardless of COX-1 Activity.

Platelets play crucial roles in cardiovascular diseases (CVDs) by regulating hemostasis and blood coagulation at sites of blood vessel damage. Accumulating evidence indicates daidzein inhibits platelet activation, but the mechanism involved has not been elucidated. Thus, in this study, we investigated the mechanism responsible for the inhibition of collagen-induced platelet aggregation by daidzein. We found that in collagen-induced platelets, daidzein suppressed the production of thromboxane A2 (TXA2), a molecule involved in platelet activation and aggregation, by inhibiting the cytosolic phospholipase A2 (cPLA2) signaling pathway. However, daidzein did not affect cyclooxygenase-1 (COX-1). Furthermore, daidzein attenuated the PI3K/PDK1/Akt/GSK3αß and MAPK (p38, ERK) signaling pathways, increased the phosphorylation of inositol trisphosphate receptor1 (IP3R1) and vasodilator-stimulated phosphoprotein (VASP), and increased the level of cyclic adenosine monophosphate (cAMP). These results suggest that daidzein inhibits granule release (ATP, serotonin, P-selectin), integrin αIIbß3 activation, and clot retraction. Taken together, our study demonstrates that daidzein inhibits collagen-induced platelet aggregation and suggests that daidzein has therapeutic potential for the treatment of platelet aggregation-related diseases such as atherosclerosis and thrombosis.

Biportal Endoscopic Posterior Thoracic Laminectomy for Thoracic Spondylotic Myelopathy Caused by Ossification of the Ligamentum Flavum: Technical Developments and Outcomes.

OBJECTIVE: Advanced biportal endoscopic surgery techniques can be used to treat thoracic myelopathy secondary to ossification of the ligamentum flavum (OLF). This case series elaborates on a feasible biportal endoscopic technique for thoracic OLF removal and evaluates clinical and radiological outcomes. METHODS: A biportal endoscopic posterior thoracic laminectomy was performed to remove the thoracic OLF. Surgical techniques have evolved from inside-out piecemeal removal methods to outside-in en bloc removal methods. Preoperative computed tomography was performed to analyze dural ossification and OLF types. Intraoperative videos were reviewed to observe dural ossification and to determine the surgical method. Neurological outcomes were assessed using the Japanese Orthopaedic Association (JOA) score. RESULTS: Clinical symptoms and neurological function improved markedly after surgery (JOA score, preoperative: 12.6 ± 1.0, final follow-up: 15.6 ± 1.2). The mean operation time per segment was not short (106.6 ± 38 minutes). At early experience stages, inside-out piecemeal decompression was used and it caused intraoperative spinal cord injury. However, outside-in en bloc decompression technique did not induce neural complications. Postoperative segmental instability and correlated mechanical back pain were not observed. CONCLUSION: The biportal endoscopic posterior thoracic approach is an attractive surgical option to treat thoracic spondylotic myelopathy secondary to OLF. Piecemeal inside-out decompression can induce irreversible spinal cord injury, especially in the early experience stages. Outside-in decompression is more efficient and safer than inside-out pattern procedures by minimizing dural manipulation. Nonetheless, this technique is technically demanding and should only be performed in selected patients after acquiring abundant experience with endoscopic spine surgeries.

Evaluation of the efficacy and safety of conventional and interlaminar full-endoscopic decompressive laminectomy to treat lumbar spinal stenosis (ENDO-F trial): Protocol for a prospective, randomized, multicenter trial.

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).

Anthocyanin Oligomers Induce Apoptosis and Autophagy by Inhibiting the mTOR Signaling Pathway in Human Breast Cancer Cells.

Anthocyanin oligomers (AOs) are phytochemicals synthesized by fermenting anthocyanins extracted from grape skins and are more biologically active than monomeric anthocyanins. In this study, we evaluate the effects of an AO on triple-negative MDA-MB-231 and HER2-overexpressing SK-BR-3 breast cancer cells. The cell viability of MDA-MB-231 and SK-BR-3 cells was significantly inhibited in a concentration-dependent manner by AO treatment for 24 h, while delphinidin (a monomeric anthocyanin) had no effect on cell viability. In addition, the AO increased H2A.X phosphorylation (a marker of DNA damage), reduced RAD51 (a DNA repair protein) and survivin (a cell survival factor) protein levels, and induced apoptosis by caspase-3-dependent PARP1 cleavage in both cell lines. Surprisingly, the AO induced autophagy by increasing intracellular LC3-II puncta and LC3-II and p62 protein levels. In addition, the AO inhibited the mTOR pathway in MDA-MB-231 and SK-BR-3 cells by suppressing the HER2, EGFR1, and AKT pathways. These results demonstrate that the anti-cancer effect of the AO was due to the induction of apoptosis and autophagy via cleaved caspase-3-mediated PARP1 cleavage and mTOR pathway inhibition, respectively. Furthermore, our results suggest that anthocyanin oligomers could be considered potential candidates for breast cancer treatment.

Indications, Contraindications, and Complications of Biportal Endoscopic Decompressive Surgery for the Treatment of Lumbar Stenosis: A Systematic Review.

BACKGROUND: Biportal endoscopic spine surgery is gaining popularity in managing degenerative lumbar diseases and has optimal indications and contraindications. The perioperative complications related to the biportal endoscopic approach affect the postoperative outcomes. Therefore, this study aimed to review the indications, contraindications, and complications of biportal endoscopic decompression for lumbar stenosis. METHODS: For this systematic review, articles on biportal endoscopic decompressive surgery for lumbar stenosis, including central, lateral recess and foraminal stenoses, were searched for and reviewed. Additionally, the complications, indications, and contraindications of biportal endoscopic surgery for lumbar stenosis were reviewed. RESULTS: Forty-one articles were included in this study. The indications for biportal endoscopic decompression are central lumbar stenosis, central stenosis with lipomatosis, lateral recess stenosis, foraminal stenosis, and the far-out syndrome. The contraindications include trauma, infection, tumor, instability, high-grade spondylolisthesis, isthmic spondylolisthesis, and severe scoliosis. Perioperative complications are typically minor; major complications include durotomy, epidural hematoma, incomplete decompression, infection, facet joint injury, neural injury, increased epidural pressure, and postoperative instability. CONCLUSIONS: Favorable indications for a biportal endoscopic approach are central lumbar, lateral recess, foraminal, extraforaminal stenoses, and the Bertolotti syndrome. Incidental durotomy and postoperative epidural hematomas are common complications of biportal endoscopic decompression.

Comparative study of the efficacy and safety of minimally invasive interlaminar full-endoscopic discectomy versus conventional microscopic discectomy in single-level lumbar herniated intervertebral disc (ENDO-F Trial): a multicenter, prospective, randomized controlled trial protocol.

BACKGROUND: Advances in minimally invasive surgery have expanded the indications for interlaminar full-endoscopic discectomy. Although the clinical outcomes for this approach may be equivalent to those of conventional microscopic discectomy, the supporting evidence is still based on small, single-center, prospective, and retrospective studies. Therefore, a multicenter randomized controlled trial is warranted. METHODS: This will be a prospective, multicenter, randomized controlled trial comparing the efficacy and safety of interlaminar full-endoscopic discectomy to those of conventional microscopic discectomy. The trial will enroll 100 participants with a lumbar disc herniation, 50 in each group. The primary outcome will be the Oswestry Disability Index (ODI) score at 12 months post-surgery. Secondary outcomes will be back and leg pain (visual analog scale); the ODI; the EuroQol-5-dimension score; patient satisfaction; and walking distance/time and time to return to daily activities post-surgery. Surgical outcomes will include postoperative drainage, operative time, duration of hospital stay, postoperative creatine kinase level as an indicator of muscle injury, and postoperative scarring. Postoperative magnetic resonance imaging, computed tomography, and simple radiography will be performed to evaluate radiographic outcomes between the two surgical approaches. Surgery-related complications and adverse effects will be evaluated as safety outcomes. A single assessor at each participating hospital, blinded to group allocation, will assess the enrolled participants at baseline, at 2 weeks, and at 3, 6, and 12 months postoperatively. DISCUSSION: This trial is designed to determine whether interlaminar full-endoscopic discectomy is clinically comparable to microscopic discectomy to treat lumbar disc herniations. All efforts will be made to reduce bias, including adequate sample size, blinded analyses, and multicenter prospective registration. The outcomes will inform practice, providing the evidence needed for using interlaminar full-endoscopic over microscopic discectomy by confirming the potential of this technique to improve patient satisfaction and clinical outcomes. TRIAL REGISTRATION: Clinical Research Information Service; cris.nih.go.kr. (KCT0006277); protocol version (v1, June 8, 2021).

Comparative Analysis of 3 Types of Minimally Invasive Posterior Cervical Foraminotomy for Foraminal Stenosis, Uniportal-, Biportal Endoscopy, and Microsurgery: Radiologic and Midterm Clinical Outcomes.

OBJECTIVE: The aim of this study was to compare the clinical and radiologic outcomes of 3 types of minimally invasive posterior cervical foraminotomy (PCF): uniportal endoscopic surgery, biportal endoscopic surgery, and microsurgery. METHODS: Between January 2019 to January 2020, PCF was performed using 3 different approaches to treat foraminal stenosis. The foraminal expansion rate, facet resection rate, and surgical foraminal approach angle were measured using magnetic resonance imaging. Visual analogue scale (VAS) scores for neck and arm pain, neck disability index (NDI), MacNab criteria, operation time, hospital stay, and complications were assessed. Clinical and radiologic parameters were compared among the 3 surgical groups. RESULTS: There were 38, 30, and 50 patients in the uniportal endoscopy, biportal endoscopy, and microscopy groups, respectively. Microscopy group displayed significantly higher foraminal expansion compared to uniportal endoscopy group (p = 0.001). Facet resection rates and inclination angle for facet joint undercutting were significantly different among the 3 groups. Uniportal endoscopy group had the highest inclination angle and the least facet resection. On the 6 months and final follow-up, VAS scores and NDI were significantly lower in the uniportal endoscopy group than in the microscopy group (p = 0.000). CONCLUSION: All 3 types of PCF displayed favorable clinical outcomes and sufficient expansion of the midforaminal area. Two endoscopy groups showed a significantly higher inclination angle for undercutting the facet joint and a lower facet resection rate than the microscopy group. Reduced facet joint resection using an inclinatory approach did not interfere with sufficient foraminal expansion and enhanced the clinical result after 6 months of follow-up.

Development of a Gas Chromatography-Flame Ionization Method for the Detection and Quantification of 12 Flavoring Agents in Supplementary Feed.

A flavoring agent is a compound that serves to add flavor with a pleasant scent and is used as a feed additive. Current flavor analysis methods include reflux pretreatment, titration, neutralization titration, and inversion; these are all analytical methods in which deviations and errors between experiments are generated. Titration methods are characterized by difficult selectivity analysis both for mixtures containing two or more types of flavoring agents and also for very low content samples. Current analysis methods are therefore particularly unsuitable for these sample types. Thus, more precise and accurate analysis of flavor agents is needed. This study intends to develop and verify a multi-component simultaneous analysis method that can accurately confirm the guaranteed content of 12 flavor agents of supplementary feeds distributed in the market, the goal being to establish a universally trusted method. Method validation was performed according to the International Conference on Harmonization (ICH) and International Union of Pure and Applied Chemistry (IUPAC) guidelines. Method validation was performed in terms of linearity, sensitivity, selectivity, accuracy, and precision. The limits of detection (LOD) for the instrument employed in these experiments ranged from 0.44-4.77 mg/kg, and the limits of quantification (LOQ) ranged from 1.32-14.31 mg/kg. Average recoveries of the 12 flavoring agents ranged from 75.1-111.4%. Maximum %RSD values for intraday and interday peak area variation are 13.09% and 13.08%, respectively. A novel and simple method for detecting 12 flavoring agents in animal feed supplements using a gas chromatography-flame ionization detector (GC-FID) was developed.