Comprehensive Proteome Profiling of Platelet Identified a Protein Profile Predictive of Responses to An Antiplatelet Agent Sarpogrelate

Sarpogrelate is an antiplatelet agent widely used to treat arterial occlusive diseases. Evaluation of platelet aggregation is essential to monitor therapeutic effects of sarpogrelate. Currently, no molecular signatures are available to evaluate platelet aggregation. Here, we performed comprehensive proteome profiling of platelets collected from 18 subjects before and after sarpogrelate administration using LC-MS/MS analysis coupled with extensive fractionation. Of 5423 proteins detected, we identified 499 proteins affected by sarpogrelate and found that they strongly represented cellular processes related to platelet activation and aggregation, including cell activation, coagulation, and vesicle-mediated transports. Based on the network model of the proteins involved in these processes, we selected three proteins (cut-like homeobox 1; coagulation factor XIII, B polypeptide; and peptidylprolyl isomerase D) that reflect the platelet aggregation-related processes after confirming their alterations by sarpogrelate in independent samples using Western blotting. Our proteomic approach provided a protein profile predictive of therapeutic effects of sarpogrelate. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.1

SEALONE (Safety and Efficacy of Coronary Computed Tomography Angiography with Low Dose in Patients Visiting Emergency Room) trial: study protocol for a randomized controlled trial

Objective Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. Methods The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. Results and Conclusion Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Effect of α1D-adrenoceptor blocker for the reduction of ureteral contractions

Purpose: Urolithiasis is a common urinary tract disease with growing prevalence. Alpha1-adrenoceptors (α1-ARs) are abundant in ureteral smooth muscle, distributed with different α1-AR subtypes. α1D-AR is the most widely distributed in the ureter. However, the effect of α1D-AR blockade on ureteric contraction remains unknown. Materials and Methods: We dissected smooth muscle tissues (3 mm×3 mm) from the rat bladder and human ureter, tied silk strips on both tissue ends, and measured contraction in an organ bath chamber. Contraction activity in ureteral smooth muscle cells (USMCs) was immunocytochemically examined using primary rat and human USMC cultures. Results: Using the organ bath system, we determined the inhibitory effects of silodosin, tamsulosin, and naftopidil. Naftopidil significantly decreased contractility of rat bladder tissue; similar results were observed in human ureteral tissue. To confirm ex vivo experimental results in vitro , we examined the phosphorylation of myosin light chain (MLC), a marker of contractility, in a primary human USMC culture. The examined drugs decreased phospho-MLC levels in human USMCs; however, naftopidil profoundly increased MLC dephosphorylation. Conclusions: We studied the effects of naftopidil, an α1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones

The complete mitochondrial genome of Japanese sea lion, Zalophus japonicus (Carnivora: Otariidae) analyzed using the excavated skeletal remains from Ulleungdo, South Korea

The Japanese sea lion, Zalophus japonicus, is an extinct pinniped species, which had inhabited along the coast of the Japanese archipelago and Korean peninsula. Its mitochondrial genome was determined by the assembly of PCR amplicons from the skeletal remains excavated from the Ulleungdo, South Korea. The whole mitogenome was 16,698 bp in length, which encoded 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNA), 2 ribosomal RNAs (rRNA), an origin of light-strand replication (OL), and a control region (D-loop). Unusual start codons were identified in ND2 (ATA), ND3 (ATA), and ND5 (ATC), while COIII, ND3, and ND4 were terminated with an incomplete stop codon (T–/TA-). Phylogenetic analysis showed that Z. japonicus was a sister species to Z. californianus with 98.61% nucleotide sequence identity among 11 pinniped species in the infraorder Pinnipedia, which supported the previous results. The complete mitochondrial genome sequence of Z. japonicus would be valuable information for its restoration and the evolutional understandings of pinniped species in the Pacific Ocean

Corrigendum: Improvement of Persistent Detrusor Overactivity through Treatment with a Phytotherapeutic Agent (WSY-1075) after Relief of Bladder Outlet Obstruction

Purpose: Many patients with benign prostatic hyperplasia need treatment for remaining storage symptoms after surgery. Therefore, we evaluated the effect of the phytotherapeutic agent WSY-1075 on persistent detrusor overactivity (DO) after the relief of bladder outlet obstruction (BOO). Materials and Methods: Rats were assigned to 3 groups: control (n=6), persistent DO (n=6), and persistent DO treated with the phytotherapeutic agent WSY-1075 (n=6). Persistent DO after relief of partial BOO was generated in the rat model, and 6 of the rats with this condition were orally administered WSY-1075. After 4 weeks of administration, cystometry was performed. Additionally, 8-hydroxy-2-deoxyguanosine and superoxide dismutase were measured to evaluate oxidative stress in the bladder. Pro-inflammatory cytokines, such as interleukin-8 and tumor necrosis factor-α, were analyzed, as were the M2 and M3 muscarinic receptors of the bladder. Results: Significantly increased contraction pressure and a decreased contraction interval were observed in the persistent DO group after relief of BOO. Moreover, oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors were significantly increased. After treatment with WSY-1075, significantly reduced DO was observed by cystometry in comparison with the persistent DO group. Additionally, significantly decreased levels of oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors in the bladder were observed after treatment with WSY-1075. Conclusions: Treatment with WSY-1075 improved persistent DO after the relief of BOO mediated by antioxidative and antiinflammatory effects. Further studies are necessary to identify the exact mechanism of the treatment effect of WSY-1075

An Asian traditional herbal complex containing Houttuynia cordata Thunb, Perilla frutescens Var. acuta and green tea stimulates hair growth in mice

Abstract Background Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely used in Asia for the treatment of patients with alopecia, usually in combination with other two herbal medicines (Perilla frutescens var. acuta (PFVA) and green tea (GT)). However, the effect of this herbal complex has not been clearly demonstrated. We sought to determine the hair growth-promoting effect of this herbal complex (HC, PFVA, and GT) in the animal model. Methods Six-week-old male C57BL/6 mice were randomly divided into four groups (negative control, finasteride (1 mg/kg) as a positive control, and two (200 and 400 mg/kg) concentrations of the herbal complex as experimental groups) and were fed its corresponding medications orally for 25 days. Hair growth was evaluated visually and microscopically. Western blot analysis for insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1 was performed. Results The herbal complex exhibited hair growth-promoting activity in C57BL/6 mice. Grossly, the area of hair regrowth was 55.1 (±3.8) %, 70.2 (±6.3) % and 83.5 (±5.7) % in negative control, herbal complex 200 mg/kg and 400 mg/kg group, respectively. In histologic examination, the hair follicle count in deep subcutis was 2.6 (±0.7), 5.8 (±0.7) and 8.6 (±1.2) and the diameter of hair follicles was 11.9 (±5.0) μm, 17.4 (±3.9) μm and 22.8 (±5.2) μm in negative control, herbal complex 200 and 400 mg/kg group, respectively. The expression of IGF-1 was 0.14 (±0.01), 0.23 (±0.02) and 0.24 (±0.01) and the expression of TGF-β1 was 0.26 (±0.01), 0.19 (±0.02) and 0.15 (±0.01) in negative control, the 200 and 400 mg/kg group, respectively. Conclusions This data provides adequate preliminary experimental evidence to support the hair regeneration effect of this herbal complex

Transcriptome Profile of the Asian Giant Hornet (Vespa mandarinia) Using Illumina HiSeq 4000 Sequencing: De Novo Assembly, Functional Annotation, and Discovery of SSR Markers

Vespa mandarinia found in the forests of East Asia, including Korea, occupies the highest rank in the arthropod food web within its geographical range. It serves as a source of nutrition in the form of Vespa amino acid mixture and is listed as a threatened species, although no conservation measures have been implemented. Here, we performed de novo assembly of the V. mandarinia transcriptome by Illumina HiSeq 4000 sequencing. Over 60 million raw reads and 59,184,811 clean reads were obtained. After assembly, a total of 66,837 unigenes were clustered, 40,887, 44,455, and 22,390 of which showed homologous matches against the PANM, Unigene, and KOG databases, respectively. A total of 15,675 unigenes were assigned to Gene Ontology terms, and 5,132 unigenes were mapped to 115 KEGG pathways. The zinc finger domain (C2H2-like), serine/threonine/dual specificity protein kinase domain, and RNA recognition motif domain were among the top InterProScan domains predicted for V. mandarinia sequences. Among the unigenes, we identified 534,922 cDNA simple sequence repeats as potential markers. This is the first transcriptomic analysis of the wasp V. mandarinia using Illumina HiSeq 4000. The obtained datasets should promote the search for new genes to understand the physiological attributes of this wasp