Scoping review protocol of post-traumatic growth (PTG) in Korean cancer survivors.

INTRODUCTION: Cancer, a life-threatening chronic disease, is the leading cause of death in Korea, accounting for 27% of all deaths in 2020. Due to advancements in medical technology and early detection of cancer in Korea, the 5-year relative survival rate reached 70.7% (2015-2019), highlighting remarkable progress over the past decades. Although cancer has been seen as a traumatic event, cancer survivors also go through a subjective process of self-maturation, which is called post-traumatic growth (PTG). Because research on PTG among Korean cancer survivors has not been systematically synthesised, a scoping review on this topic will provide a better understanding of the positive psychological changes that occur as a patient moves through the illness trajectory of cancer from a Korean cultural perspective. The purpose of this study was to describe the protocol of a scoping review regarding PTG in Korean cancer survivors. METHODS AND ANALYSIS: The scoping review framework suggested by Arksey and O'Malley and the manual refined by the Joanna Briggs Institute for scoping reviews will be used with the six framework guidelines developed by Levac et al. Searched databases will include Ovid-MEDLINE, PubMed, Embase, CINAHL, Cochrane Library and PsycInfo, as well as Korean databases, examining all articles published between 2012 and 2023 in Korean or English on PTG in Korean cancer survivors. Extracted data will be collated, charted and summarised. ETHICS AND DISSEMINATION: Because the scoping review methodology undertakes a secondary analysis of collected data from previous research studies, this study does not require ethical approval. The results of this scoping review will be disseminated through presentations at conferences and publication in a scientific journal.

The impact of a modified microbiota-accessible carbohydrate diet on gut microbiome and clinical symptoms in colorectal cancer patients following surgical resection.

A high-fiber diet is widely recognized for its positive effects on the gut microbiome. However, the specific impact of a high-fiber diet on the gut microbiome and bowel habits of patients with colon cancer remains poorly understood. In this study, we aimed to assess the effects of a modified microbiota-accessible carbohydrate (mMAC) diet on gut microbiota composition and clinical symptoms in colon cancer patients who underwent surgical resection. To achieve this, we enrolled 40 patients in two groups: those who received adjuvant chemotherapy and those who did not. Fecal samples were collected before and after dietary interventions for microbial and metabolite analyses. Each group was randomized in a 1: 1 ratio to follow either a 3-week conventional diet followed by a 3-week mMAC diet, or the reverse sequence. Although there were no significant differences in the microbial diversity data before and after the mMAC diet in both the non-chemotherapy and chemotherapy groups, distinct differences in gut microbial composition were revealed after the mMAC diet. Specifically, the abundance of Prevotella, which is associated with high-fiber diets, was further elevated with increased concentrations of acetate and propionate after the mMAC diet. Additionally, patients who experienced improved diarrhea and constipation after the mMAC diet exhibited an enrichment of beneficial bacteria and notable changes in metabolites. In conclusion, this study provides valuable insights into the potential benefits of the mMAC diet, specifically its impact on the gut microbiome and clinical symptoms in postoperative colorectal cancer (CRC) patients. These findings emphasize the potential role of a high-fiber diet in influencing the gut microbiome, and the clinical symptoms warrant further investigation.

A one-pot transcriptional assay method that detects the tumor biomarker FEN1 based on its flap cleavage activity.

BACKGROUND: Detection of tumor biomarkers in body fluids is a significant advancement in cancer treatment because it allows diagnosis without invasive tissue biopsies. Nucleases have long been regarded as a potential class of biomarkers that can indicate the occurrence and progression of cancers. Among these, flap endonuclease 1 (FEN1) plays an important role in DNA replication and repair, and also overexpressed in abnormally proliferating cells such as cancer cells. FEN1 is thus considered to be a potential biomarker as well as a target for cancer therapy. RESULTS: We developed a novel method for detecting FEN1 based on its specific endonuclease activity which incises bifurcated nucleic acids (flaps), in combination with in vitro transcription. Developed method uses a simple DNA structure (substrate DNA) carrying a short 5'-flap sequence, and a single-stranded sensor DNA encoding the Broccoli light-up aptamer. When the assay mixture was supplied with a FEN1-containing sample, the flap sequence encoding the sense sequence of T7 promoter was cleaved and released from the substrate DNA. Because the sensor DNA was designed to carry the Broccoli RNA aptamer under the antisense sequence of T7 promoter, hybridization of the excised flap onto the sensor DNA initiated the transcription of the Broccoli RNA aptamer, enabling determination of the FEN1 titer based on the fluorescence of transcribed Broccoli aptamer. By using a combination of FEN1-mediated generation of a short oligonucleotide and subsequent oligonucleotide-dependent in vitro transcription, this method could detect FEN1 in biological samples within 1 h. SIGNIFICANCE AND NOVELTY: Developed method enables the detection of FEN1 by a simple one-pot reaction. It can detect sub-nanomolar concentrations of FEN1 within an hour, and has the potential to be used for cancer diagnosis, prognosis, and drug screening. It also enables easy identification of compounds that inhibit FEN1 activity and is thus a versatile platform for screening anti-cancer drugs. We anticipate that the basic principles of this assay can be applied to detect other biomolecules, such as nucleic acids.

A Novel Tactile Sensing System Utilizing Magnetorheological Structures for Dynamic Contraction and Relaxation Motions.

It is well known that the rheological properties of magnetorheological (MR) material change under a magnetic field. So far, most works on MR materials have been oriented toward actuating characteristics instead of sensing functions. In this work, to realize dynamic tactile motion, a spherical MR structure was designed as a sensor, incorporating a magnetic circuit core to provide maximum dynamic motion. After manufacturing a prototype (sample), a sinusoidal magnetic field of varying exciting frequency and magnitude was applied to the sample, and the dynamic contraction and relaxation motion depending on the exciting magnetic field was observed. Among the test results, when 10% deformation occurred, the instantaneous force generated was from 2.8 N to 8.8 N, and the force when relaxed was from 1.2 N to 3.5 N. It is also shown that the repulsive force within this range can be implemented using an acceptable input current. The special tactile sensing structure proposed in this work can be used as a sensor to measure the field-dependent viscoelastic properties of human tissues such as stomach, liver, and overall body. In addition, it could be usefully applied to robot surgery, because it can mimic the dynamic motions of various human organs under various surgical conditions.

Examining Final-Administered Medication as a Measure of Data Quality: A Comparative Analysis of Death Data with the Central Cancer Registry in Republic of Korea.

Death is a crucial outcome in retrospective cohort studies, serving as a criterion for analyzing mortality in a database. This study aimed to assess the quality of extracted death data and investigate the potential of the final-administered medication as a variable to quantify accuracy for the validation dataset. Electronic health records from both an in-hospital and the Korean Central Cancer Registry were used for this study. The gold standard was established by examining the differences between the dates of in-hospital deaths and cancer-registered deaths. Cosine similarity was employed to quantify the final-administered medication similarities between the gold standard and other cohorts. The gold standard was determined as patients who died in the hospital after 2006 and whose final hospital visit/discharge date and death date differed by 0 or 1 day. For all three criteria-(a) cancer stage, (b) cancer type, and (c) type of final visit-there was a positive correlation between mortality rates and the similarities of the final-administered medication. This study introduces a measure that can provide additional accurate information regarding death and differentiates the reliability of the dataset.

A New Tactile Transfer Cell Using Magnetorheological Materials for Robot-Assisted Minimally Invasive Surgery.

This paper proposes a new type of tactile transfer cell which can be effectively applied to robot-assisted minimally invasive surgery (RMIS). The proposed tactile device is manufactured from two smart materials, a magnetorheological fluid (MRF) and a magnetorheological elastomer (MRE), whose viscoelastic properties are controllable by an external magnetic field. Thus, it can produce field-dependent repulsive forces which are equivalent to several human organs (or tissues) such as a heart. As a first step, an appropriate tactile sample is made using both MRF and MRE associated with porous foam. Then, the microstructures of these materials taken from Scanning Electron Microscope (SEM) images are presented, showing the particle distribution with and without the magnetic field. Subsequently, the field-dependent repulsive force of the sample, which is equivalent to the stress relaxation property of viscoelastic materials, are measured at several compressive deformation depths. Then, the measured values are compared with the calculated values obtained from Young's modulus of human tissue data via the finite element method. It is identified from this comparison that the proposed tactile transfer cell can mimic the repulsive force (or hardness) of several human organs. This directly indicates that the proposed MR materials-based tactile transfer cell (MRTTC in short) can be effectively applied to RMIS in which the surgeon can feel the strength or softness of the human organ by just changing the magnetic field intensity. In this work, to reflect a more practical feasibility, a psychophysical test is also carried out using 20 volunteers, and the results are analyzed, presenting the standard deviation.

Expanding the Non-Invasive Diagnosis of Acute Rejection in Kidney Transplants Through Detection of Donor-Derived DNA in Urine: Proof-of-Concept Study.

BACKGROUND: Approximately 10%-20% of kidney transplant (KT) recipients suffer from acute rejection (AR); thus, sensitive and accurate monitoring of allograft status is recommended. We evaluated the clinical utility of donor-derived DNA (dd-DNA) detection in the urine of KT recipients as a non-invasive means for diagnosing AR. METHODS: Urine samples serially collected from 39 KT recipients were tested for 39 single-nucleotide variant loci selected according to technical criteria (i.e., high minor allele frequency and low analytical error) using next-generation sequencing. The fraction of dd-DNA was calculated and normalized by the urine creatinine (UCr) level (%dd-DNA/UCr). The diagnostic performance of %dd-DNA/UCr for AR was assessed by ROC curve analysis. RESULTS: There was an increasing trend of %dd-DNA/UCr in the AR group before subsequent graft injury, which occurred before (median of 52 days) histological rejection. The serum creatinine (SCr) level differed significantly between the AR and non-AR groups at two and four months of follow-up, whereas %dd-DNA/UCr differed between the groups at six months of follow-up. The combination of %dd-DNA/UCr, SCr, and spot urine protein (UPtn)/UCr showed high discriminating power, with an area under the ROC curve of 0.93 (95% confidence interval: 0.81-1.00) and a high negative predictive value of 100.0%. CONCLUSIONS: Although the dd-DNA-based test cannot eliminate the need for biopsy, the high negative predictive value of this marker could increase the prebiopsy probability of detecting treatable injury to make biopsy an even more effective diagnostic tool.

Chimerism Assay Using Single Nucleotide Polymorphisms Adjacent and in Linkage-Disequilibrium Enables Sensitive Disease Relapse Monitoring after Hematopoietic Stem-Cell Transplantation.

BACKGROUND: Short tandem repeat (STR)-based chimerism analysis has been widely used for chimerism monitoring after hematopoietic stem-cell transplantation (HSCT), but technical artifacts can be problematic. We designed a chimerism assay using single nucleotide polymorphisms (SNPs) adjacent and in linkage-disequilibrium (CASAL), which doubly checked for SNP pairs, and thus could reduce background errors and increase analytical sensitivity. METHODS: CASAL targeted 84 SNP pairs within 10 bp distance and in perfect linkage-disequilibrium. Using undiluted and serially diluted samples, baseline error rates, and linearity was calculated. Clinical performance of CASAL was evaluated in comparison with a conventional STR assay, using 191 posttransplant samples from 42 patients with HSCT. RESULTS: CASAL had ∼10 times lower baseline error rates compared to that of ordinary next-generation sequencing. Limit of detection and quantification of CASAL were estimated to be 0.09 and 0.39%, respectively, with a linear range of 0.1-100%. CASAL correlated well with STR assay (r2 = 0.99) and the higher sensitivity enabled detection of low-level recipient chimerism and earlier prediction of relapse. CONCLUSIONS: CASAL is a simple, analytically sensitive and accurate assay that can be used in clinical samples after HSCT with a higher performance compared to that of traditional assays. It should also be useful in other forensic and archeological testing.

Multiple microRNAs as biomarkers for early breast cancer diagnosis.

MicroRNA (miRNA or miR) is stably present in plasma. It has been reported that miRNA could be used for detecting cancer. Circulating miRNAs are being increasingly recognized as powerful biomarkers in a number of different pathologies, including in breast cancer. The aim of the current study was to establish and validate miRNA sets that are useful for the early diagnosis of breast cancer. Specifically, the current study intended to determine whether miRNA biomarkers were tumor-specific and to statistically verify whether circulating miRNA analysis could be used for breast cancer diagnosis. In the present study, a total of nine candidate miRNA biomarkers were selected by examining reference miRNAs associated with the generation and progression of breast cancer to identify novel miRNAs that could be used to detect early breast cancer. A total of 226 plasma samples from patients with breast cancer were used. In addition, 146 plasma healthy samples were used as non-cancer controls. These samples were divided into training and validation cohorts. The training cohort was used to identify a combination of miRNA that could detect breast cancer. The validation cohort was used to validate this combination of miRNA. Total RNAs were isolated from collected samples. A total of 9 miRNAs were quantified using reverse-transcription quantitative PCR. A total of nine candidate miRNA expression levels were compared between patients with breast cancer and healthy controls. It was indicated that combinations of two or more of the nine miRNAs could detect breast cancer with higher accuracy than the use of a single biomarker. As a representative example, combinations of four miRNAs (miR-1246+miR-206+miR-24+miR-373) of the nine miRNAs had a sensitivity of 98%, a specificity of 96% and an accuracy of 97% for breast cancer detection in the validation cohort. The results of the present study suggest that multiple miRNAs could be used as potential biomarkers for early diagnosis of breast cancer. These biomarkers are expected to overcome limitations of mammography when used as an auxiliary diagnosis of mammography.

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study.

The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progression-free survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes.

Tunable Young's Moduli of Soft Composites Fabricated from Magnetorheological Materials Containing Microsized Iron Particles.

This study experimentally investigates the field-dependent Young's moduli of soft composites, which are fabricated from two different magnetic-responsive materials; magnetorheological elastomer (MRE) and magnetorheological fluid (MRF). Four factors are selected as the main factors affecting Young's modulus of soft composites: the amount of MRF, the channel pattern, shore hardness and carbonyl iron particle (CIP) concentration of the MRE layer. Five specimens are manufactured to meet the investigation of four factors. Prior to testing, the scanning electron microscopy (SEM) image is taken to check the uniform dispersion of the carbonyl iron particle (CIP) concentration of the MRE layer, and a magnetic circuit is constructed to generate the effective magnetic field to the specimen fixed at the universal tensile test machine. The force-displacement curve is directly measured from the machine and converted to the stress-strain relationship. Thereafter, the Young's modulus is determined from this curve by performing linear regression analysis with respect to the considered factors. The tunability of the Young's moduli of the specimens is calculated based on the experimental results in terms of two performance indicators: the relative percentage difference of Young's modulus according to the magnetic field, and the normalized index independent of the zero-field modulus. In the case of the relative percentage difference, the specimens without MRF are the smallest, and the ones with the highest CIP concentration are the largest. As a result of comparing the normalized index of each factor, the change in shore hardness and channel pattern have little effect on the tunability of Young's moduli, and the amount of MRF injected and CIP concentration of MRE have a large effect. The results of this study are expected to provide basic guidelines for fabricating soft composites whose field-dependent Young's moduli can be tuned by several factors with different effects.

Triacanthine exerts antitumor effects on bladder cancer in vitro and in vivo.

BACKGROUND: Numerous studies have focused on solvent extracts from locust trees (Gleditsia spp.), which contain diverse bioactive components including saponins, flavonoids, and alkaloids. However, because of the undefined nature of such phytochemicals, their clinical application as chemotherapeutic agents has often been limited. PURPOSE: This study aimed to evaluate the anti-oncogenic activity of triacanthine, an alkaloid obtained from Gleditsia triacanthos L. STUDY DESIGN: The anti-oncogenicity of triacanthine in vitro was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell-counting kit-8 assay (CCK-8 assay), flow cytometry, imunoblot, migration and invasion assays, zymography, and electrophoretic mobility shift assay in the human bladder carcinoma cell line EJ. The in vivo efficacy of triacanthine was evaluated via oral administration to EJ-xenografted BALB/c nude mice. To identify the side effects of triacanthine, cisplatin was also administered and an acute toxicity test was performed. RESULTS: Triacanthine significantly inhibited EJ cell proliferation (IC50 600 µM). Flow cytometry analysis revealed that cells were arrested in the G1 phase, and apoptotic cells accumulated in sub-G1 phase in a dose-dependent manner. Triacanthine inhibited the G1-S transition by deterring complex formation between cyclin-dependent kinases and cyclins, thereby up-regulating cell cycle inhibitors p21WAF1 and p27KIP1. In addition, triacanthine induced a caspase-dependent extrinsic pathway of apoptosis and autophagy. Early responsive kinases, extracellular signal-regulated kinase (ERK) and Janus kinase (JNK) were up-regulated by triacanthine. Triacanthine-mediated inhibition of the migratory and invasive potential of EJ cells was attributed to reduction of matrix metalloproteinase (MMP)-9 due to suppression of binding activities of the transcription factors activator protein (AP)-1, specificity protein (Sp)-1, and nuclear factor (NF)-κB. In an in vivo study, triacanthine significantly limited growth of xenografted tumors. Interestingly, while cisplatin resulted in significant weight loss after a 5-mg/kg dose, triacanthine did not cause weight loss, behavioral abnormalities, altered biochemical parameters, or tissue staining. A single oral dose acute-toxicity test (triacanthine 2,000 mg/kg) produced no adverse cytotoxic effects via blood biochemical tests and tissue-organ staining. CONCLUSION: To our knowledge, this is the first systematic evaluation of the anti-oncogenic activity of triacanthine. Therefore, we believe that our findings may guide the development of novel chemotherapeutic agents for bladder cancers.

Plumbagin from a tropical pitcher plant (Nepenthes alata Blanco) induces apoptotic cell death via a p53-dependent pathway in MCF-7 human breast cancer cells.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthaquinone) has displayed antitumor activity in vitro and in animal models; however, the underlying molecular mechanisms have not been fully explored. The aim of this study was to investigate the anticancer effects of plumbagin isolated from Nepenthes alata against MCF-7 breast cancer cells. We examined the cytotoxicity, cell cycle regulation, apoptotic cell death, and generation of intracellular reactive oxygen species (ROS) in MCF-7 cells. Plumbagin exhibited potent cytotoxicity in MCF-7 cells (wild-type p53) compared to that in SK-OV-3 (null-type) human epithelial ovarian cancer cells. Specifically, plumbagin upregulated the expression of p21CIP1/WAF1 in MCF-7 cells, causing cell cycle arrest in the G2/M phase through inhibition of cyclin B1 levels. Plumbagin also significantly increased the ratio of Bax/Bcl-2 and release of cytochrome c, resulting in apoptotic cell death in MCF-7 cells. Furthermore, plumbagin dramatically increased the intracellular ROS level, whereas pretreatment with the ROS scavenger N-acetyl cysteine protected against plumbagin-induced cytotoxicity, suggesting that ROS formation plays a pivotal role in antitumor activity in MCF-7 cells. In mice bearing MCF-7 cell xenografts, plumbagin significantly reduced tumor growth and weight without apparent side effects. We therefore concluded that plumbagin exerts anticancer activity against MCF-7 cells through the generation of intracellular ROS, resulting in the induction of apoptosis via a p53-dependent pathway. This study thus identifies a new anticancer mechanism of plumbagin against p53-dependent breast cancer cells and suggests a novel strategy for overcoming of breast cancer therapy.

A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation.

We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.

Novel therapeutic roles of MC-4 in combination with everolimus against advanced renal cell carcinoma by dual targeting of Akt/pyruvate kinase muscle isozyme M2 and mechanistic target of rapamycin complex 1 pathways.

Current clinical trials of new anticancer therapies against metastatic renal cell carcinoma (RCC), including molecular-targeted therapies, have not shown promise. The purpose of this study was to preclinically assess the antitumor effects of MC-4, a partially purified material of Artemisia annua L., as a monotherapy or in combination with the known mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, everolimus, against Caki-1 (Von Hippel-Lindau (VHL)+/+) and 786-O (VHL-/-) human RCC cells. MC-4 monotherapy significantly increased tumor growth inhibition and autophagic cell death in RCC cells in vitro and in vivo. Everolimus led to compensatory Akt activation by inhibiting only mTORC1 signaling pathway. In contrast to everolimus, MC-4 enhanced phosphatase and tensin homolog expression and reduced its downstream effector, Akt/pyruvate kinase muscle isozyme M2 (PKM2), leading to decreased expression of glucose transporter 1, which is associated with cancer cell metabolism. The synergistic antitumor and anti-metastatic effects induced by co-administration of MC-4 and everolimus involve cell growth inhibition and autophagic cell death via dual targeting of phosphatidylinositol 3-kinase (PI3K)/Akt/PKM2 and mTORC1. These findings suggest that MC-4 is a novel Akt/PKM2 inhibitor that can overcome the limitation of existing mTOR inhibitors and can be considered a novel strategy to treat patients with rapidly progressing advanced RCC.

Hydrangenol inhibits the proliferation, migration, and invasion of EJ bladder cancer cells via p21WAF1-mediated G1-phase cell cycle arrest, p38 MAPK activation, and reduction in Sp-1-induced MMP-9 expression.

Hydrangenol is a dihydroisocoumarin that is mainly obtained from Hydrangea macrophylla. Recently, hydrangenol has garnered attention since several studies have reported that it has anti-inflammatory, anti-allergic, anti-diabetic, and anti-malarial activities. However, there have been few studies on the effect of hydrangenol on oncogenesis. In this study, we evaluated the anti-cancer activity of hydrangenol against the EJ bladder cancer cell line. Hydrangenol significantly inhibited the proliferation of EJ cells in a dose-dependent manner with an IC50 of 100 µM. Flow cytometry and immunoblotting experiments indicated that EJ cells were arrested in the G1-phase of the cell cycle and showed reduced expression of CDK2, CDK4, cyclin D1, and cyclin E mediated via the upregulation of p21WAF1. Hydrangenol increased the phosphorylation of p38 MAPK without affecting the phosphorylation of ERK and JNK. In addition, hydrangenol significantly inhibited the migratory and invasive activities of EJ cells by suppressing the enzymatic activity of MMP-9. Electrophoretic mobility shift assays suggested that the inhibition of MMP-9 activity by hydrangenol was attributable to its suppression of the Sp-1 transcription factor binding activity. This study is the first report on the mode of action of hydrangenol as an inhibitor of bladder cancer. We believe that these results provide novel insights that could aid the development of hydrangenol-based chemotherapeutic agents.

Ratiometric detection of nanomolar concentrations of heparin in serum and plasma samples using a fluorescent chemosensor based on peptides.

A peptidyl fluorescent chemosensor for heparin was synthesized by conjugating a pyrene fluorophore with the heparin-binding peptide. The fluorescent chemosensor (Py12; pyrene-RKRLQVQLSIRT) showed a highly sensitive ratiometric response to nanomolar concentrations of heparin in aqueous solutions at physiological pH by increasing excimer emission intensity at 500 nm with a concomitant decrease in monomer emission intensity at 400 nm. Py12 showed a sensitive ratiometric response to heparin over a wide pH range (1.5 ≤ pH ≤ 11.5) and exhibited high selectivity for heparin compared to other biological competitors, such as hyaluronic acid and chondroitin sulfate. Py12 sensitively and ratiometrically detected nanomolar concentrations of heparin in biologically relevant samples containing human serum and human plasma, respectively. The detection limit of Py12 was 34 pM (R(2) = 0.997) for heparin in an aqueous buffer solutions containing 5% human serum and 33 pM (R(2) = 0.994) for heparin in aqueous buffer solutions containing 5% human plasma. Py12 had sufficient sensitivity and selectivity for ratiometrically detecting a nanomolar concentration of heparin, indicating that the peptide-base chemosensor provides a potential tool for monitoring heparin levels in clinical plasma samples.

Eight-year experience of bloodless surgery at a tertiary care hospital in Korea.

BACKGROUND: The Soonchunhyang University Hospital Bloodless Center was established in 2000, and more than 2000 bloodless surgeries has been performed there since. This study was carried out to analyze the characteristics of patients who underwent bloodless surgery and the influences of postoperative lowest hemoglobin level (H(blow)) along with the lowest postoperative Hb/preoperative Hb ratio (H(blow/pre)) on successful completion of bloodless surgery. STUDY DESIGN AND METHODS: A total of 1407 patients were included. Patients were divided according to H(blow) into not more than 7 and more than 7 g/dL groups and compared regarding use of transfusion alternatives, coexisting risk factors, and mortality rate. They were also grouped as H(blow/pre) of not more than 0.5 or more than 0.5, and mortalities were compared between them. RESULTS: Jehovah's Witnesses comprised 1323 (94.0%) of the total population. The frequency of simultaneous use of erythropoietin and iron was significantly higher in H(blow) of not more than 7 group than in more than 7 g/dL group, as was the use of hemostatics. Among risk factors urging transfusion, the frequencies of cardiovascular disease and cerebrovascular accident were higher in H(blow) of not more than 7 than in the more than 7 g/dL group. Mortality rates in H(blow) of not more than 7 g/dL and H(blow/pre) of not more than 0.5 groups were significantly higher than those in H(blow) of more than 7 g/dL and H(blow/pre) of more than 0.5 groups, respectively. CONCLUSION: We have provided an effective bloodless surgery program for the past 10 years. A prospective multicenter study with other bloodless centers in Korea concerning mortality rates, actual operative blood loss, and postoperative complications in high-risk group of patients would be needed to establish evidence-based guidelines for bloodless surgery.