Lotus Seed Green Embryo Extract and a Purified Glycosyloxyflavone Constituent, Narcissoside, Activate TRPV1 Channels in Dorsal Root Ganglion Sensory Neurons.

Several studies have documented the broad-spectrum bioactivities of a lotus seed (Plumula nelumbinis [PN]) green embryo extract. However, the specific bioactive components and associated molecular mechanisms remain largely unknown. This study aimed to identify the ion channel-activating mechanisms of PN extracts. Using fluorometric imaging and patch-clamp recordings, PN extracts were screened for calcium channel activation in dorsal root ganglion (DRG) neurons. The TRPV1 channels in DRG neurons were strongly activated by the PN extract (mean amplitude of 131 ± 45 pA at 200 µg/mL) and its purified glycosyloxyflavone narcissoside (401 ± 271 pA at 100 µM). Serial treatment with a 200 µg/mL PN extract in TRPV1-overexpressing HEK293T cells induced robust desensitization to 10 ± 10% of the initial current amplitude. Thus, we propose that the PN extract and narcissoside function as TRPV1 agonists. This new finding may advance our knowledge regarding the traditional and scientific functions of PN in human health and disease.

Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system.

Sargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.

Identification of peptide inhibitors of matrix metalloproteinase 1 using an in-house assay system for the enzyme.

Matrix metalloproteinases (MMPs) are zinc-dependent proteases involved in the degradation of extracellular matrix proteins. As one of the isoforms, MMP-1 breaks down collagen, and its activity is known to be important in wound healing. Its timely and adequate level of expression is pivotal because MMP-1 is also involved in the damage or aging of skins as well as in certain types of cancers. Thus, both assaying the MMP-1 activity and developing its inhibitors are of great importance. We here developed an in-house assay system that gave us the high degree of freedom in screening peptide inhibitors of MMP-1. The assay system utilized a circularly permutated fusion of ß-lactamase and its inhibitory protein through an MMP-1-sensitive linker so that the activity of MMP-1 could be translated into that of ß-lactamase. As a proof of concept, we applied the developed assay system to initial screens of MMP-1 inhibitors and successfully identified one lead peptide that inhibited the collagenase activity of the enzyme.

Povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound-guided prostate biopsy are associated with reduced incidence of postoperative infectious complications.

PURPOSE: The aim of this study was to evaluate the effect of povidone-iodine rectal disinfection and targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound-guided prostate biopsy based on rectal swab culture results. METHODS: From January 2011 to December 2015, we studied differences in infectious complications in men who received povidone-iodine rectal disinfection with targeted antimicrobial prophylaxis and those who received empirical prophylaxis before transrectal ultrasound-guided prostate biopsy. Clinical variables including demographics, prior antibiotic, rectal swab culture results, povidone-iodine rectal cleansing, antibiotic prophylaxis, and infectious complications were evaluated. Patients were divided into three groups as follows: Group A received no povidone-iodine rectal cleansing but received empirical antimicrobial prophylaxis; group B received povidone-iodine rectal cleansing and empirical antimicrobial prophylaxis; and group C received povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis. RESULTS: Patients were divided into group A (n = 192; 13.2 %), group B (n = 579; 39.9 %), or group C (n = 679; 46.8 %). In groups A and B, all patients received fluoroquinolone antimicrobial prophylaxis. Group C patients received targeted antimicrobial prophylaxis according to antibiotic resistance of rectal flora, and 71.1 % of these received fluoroquinolone antimicrobial prophylaxis. Infectious complication rates were 3.6, 2.9, and 1.3 % in group A, group B, and group C, respectively. Incidences of acute prostatitis and bacteremia were significantly lower in group C (p = 0.041 and p = 0.049, respectively) than in the other groups. CONCLUSIONS: In the era of quinolone resistance, the combination of povidone-iodine rectal cleansing and targeted antibiotic prophylaxis may reduce the rate of infectious complications.

Genetic Code Expansion by Degeneracy Reprogramming of Arginyl Codons.

The genetic code in most organisms codes for 20 proteinogenic amino acids or translation stop. In order to encode more than 20 amino acids in the coding system, one of stop codons is usually reprogrammed to encode a non-proteinogenic amino acid. Although this approach works, usually only one amino acid is added to the amino acid repertoire. In this study, we incorporated non-proteinogenic amino acids into a protein by using a sense codon. As all the codons are allocated in the universal genetic code, we destroyed all the tRNA(Arg) in a cell-free protein synthesis system by using a tRNA(Arg) -specific tRNase, colicin D. Then by supplementing the system with tRNACCU , the translation system was partially restored. Through this creative destruction, reprogrammable codons were successfully created in the system to encode modified lysines along with the 20 proteinogenic amino acids.

Application of bone scans for prostate cancer staging: Which guideline shows better result?

INTRODUCTION: We evaluated the accuracy of current guidelines by analyzing bone scan results and clinical parameters of patients with prostate cancer to determine the optimal guideline for predicting bone metastasis. METHODS: We retrospectively analyzed patients who were diagnosed with prostate cancer and who underwent a bone scan. Bone metastasis was confirmed by bone scan results with clinical and radiological follow-up. Serum prostate-specific antigen, Gleason score, percent of positive biopsy core, clinical staging and bone scan results were analyzed. We analyzed diagnostic performance in predicting bone metastasis of the guidelines of the European Association of Urology (EAU), American Urological Association (AUA), and the National Comprehensive Cancer Network (NCCN) guidelines as well as Briganti's classification and regression tree (CART). We also compared the percent of positive biopsy core between patients with and without bone metastases. RESULTS: A total 167 of 806 patients had bone metastases. Receiver operating curve analysis revealed that the AUA and EAU guidelines were better for detecting bone metastases than were Briganti's CART and NCCN. No significant difference was observed between AUA and EAU guidelines. Patients with bone metastases had a higher percent positive core than did patients without metastasis (the cut-off value >55.6). CONCLUSION: The EAU and AUA guidelines showed better results than did Briganti's CART and NCCN for predicting bone metastasis in the enrolled patients. A bone scan is strongly recommended for patients who have a higher percent positive core and who meet the EAU and AUA guidelines.

Enhanced splicing correction effect by an oligo-aspartic acid-PNA conjugate and cationic carrier complexes.

Peptide nucleic acids (PNAs) are synthetic structural analogues of DNA and RNA. They recognize specific cellular nucleic acid sequences and form stable complexes with complementary DNA or RNA. Here, we designed an oligo-aspartic acid-PNA conjugate and showed its enhanced delivery into cells with high gene correction efficiency using conventional cationic carriers, such as polyethylenimine (PEI) and Lipofectamine 2000. The negatively charged oligo-aspartic acid-PNA (Asp(n)-PNA) formed complexes with PEI and Lipofectamine, and the resulting Asp(n)-PNA/PEI and Asp(n)-PNA/Lipofectamine complexes were introduced into cells. We observed significantly enhanced cellular uptake of Asp(n)-PNA by cationic carriers and detected an active splicing correction effect even at nanomolar concentrations. We found that the splicing correction efficiency of the complex depended on the kind of the cationic carriers and on the number of repeating aspartic acid units. By enhancing the cellular uptake efficiency of PNAs, these results may provide a novel platform technology of PNAs as bioactive substances for their biological and therapeutic applications.

Prostate cancer with solitary metastases to the bilateral testis.

We present the case of an 81-year-old patient with testicular metastasis from prostate carcinoma. After the initial diagnosis of prostate cancer, he had an 8-year course of hormonal therapy and showed no clinical evidence of metastasis to other organs. Asymptomatic metastasis of prostate carcinoma to the testis is a rare clinical condition. We diagnosed his condition, based on histopathology following a subcapsular orchiectomy and transurethral resection of the prostate.

Subcutaneous metallic mercury injection for penile augmentation.

Mercury intoxication is rare. Most often it is associated with occupational exposure or suicide attempts. We present the case of a 72-year-old patient who received a subcutaneous injection of metallic mercury into his penis for the purpose of penile aesthetic augmentation. Total phallectomy and perineal urethrostomy was performed, followed by chelation therapy. To our knowledge, this is the first report of penile subcutaneous mercury injection for aesthetic augmentation.