ABSTRACT
Childhood and adolescence are crucial periods for developing one's awareness of sexuality. Comprehensive Sexuality Education (CSE) during these stages is essential for overall growth, fostering healthy self-concepts, and addressing diverse sexual issues among children and adolescents globally. A meta-analysis was conducted to analyze the effectiveness of CSE programs. A literature search was performed on EMBASE, PubMed, CINAHL, Cochrane Library, and PsycInfo for studies published before 14 June 2023, and based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We used the Comprehensive Meta-Analysis (CMA, V4) software version 4.0 for the analysis and interpreted the effect sizes according to Cohen's definition. Between 2011 and 2020, 21 studies on CSE were published, with the United States having the most publications (17). Of the 34 studies reviewed, 20 were randomized controlled trials. The primary population for CSE was middle/high school students (15), with the most frequent age range being 10-19 years (26). The overall effect size of CSE was significant (effect size = 1.31, p < 0.001), with cognition (effect size = 5.76, p < 0.001) being the most significant. CSE is an effective educational tool for children and adolescents with a significant impact on variables such as cognition and abstinence. It should be incremental from childhood and adolescence to adulthood.
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In this study, the characteristics of the SKD61 material used for the stem of an extruder were analyzed through structural analysis, tensile testing, and fatigue testing. The extruder works by pushing a cylindrical billet into a die with a stem to reduce its cross-sectional area and increase its length, and it is currently used to extrude complex and diverse shapes of products in the field of plastic deformation processes. Finite element analysis was used to determine the maximum stress on the stem, which was found to be 1152 MPa, lower than the yield strength of 1325 MPa obtained from tensile testing. Fatigue testing was conducted using the stress-life (S-N) method, considering the characteristics of the stem, and statistical fatigue testing was employed to create an S-N curve. The predicted minimum fatigue life of the stem at room temperature was 424,998 cycles at the location with the highest stress, and the fatigue life decreased with increasing temperature. Overall, this study provides useful information for predicting the fatigue life of extruder stems and improving their durability.
ABSTRACT
Targets of immune checkpoint inhibitors (ICIs) regulate immune homeostasis and prevent autoimmunity by downregulating immune responses and by inhibiting T cell activation. Although ICIs are widely used in immunotherapy because of their good clinical efficacy, they can also induce autoimmune-related adverse events. Thyroid-related adverse events are frequently associated with anti-programmed cell death 1 (PD-1) or anti-programmed cell death-ligand 1 (PD-L1) agents. The present study aims to investigate the factors associated with thyroid dysfunction in patients receiving PD-1 or PD-L1 inhibitors and to develop various machine learning approaches to predict complications. A total of 187 patients were enrolled in this study. Logistic regression analysis was conducted to investigate the association between such factors and adverse events. Various machine learning methods were used to predict thyroid-related complications. After adjusting for covariates, we found that smoking history and hypertension increase the risk of thyroid dysfunction by approximately 3.7 and 4.1 times, respectively (95% confidence intervals (CIs) 1.338-10.496 and 1.478-11.332, p = 0.012 and 0.007). In contrast, patients taking opioids showed an approximately 4.0-fold lower risk of thyroid-related complications than those not taking them (95% CI 1.464-11.111, p = 0.007). Among the machine learning models, random forest showed the best prediction, with an area under the receiver operating characteristic of 0.770 (95% CI 0.648-0.883) and an area under the precision-recall of 0.510 (95%CI 0.357-0.666). Hence, this study utilized various machine learning models for prediction and showed that factors such as smoking history, hypertension, and opioids are associated with thyroid-related adverse events in cancer patients receiving PD-1/PD-L1 inhibitors.
ABSTRACT
A multi-stage cold forging process was developed and complemented with finite element analysis (FEA) to manufacture a high-strength one-body input shaft with a long length body and no separate parts. FEA showed that the one-body input shaft was manufactured without any defects or fractures. Experiments, such as tensile, hardness, torsion, and fatigue tests, and microstructural characterization, were performed to compare the properties of the input shaft produced by the proposed method with those produced using the machining process. The ultimate tensile strength showed a 50% increase and the torque showed a 100 Nm increase, confirming that the input shaft manufactured using the proposed process is superior to that processed using the machining process. Thus, this study provides a proof-of-concept for the design and development of a multi-stage cold forging process to manufacture a one-body input shaft with improved mechanical properties and material recovery rate.
ABSTRACT
For the immediate detection of gaseous strong acids, it is advantageous to employ colorimetric textile sensors based on halochromic dyes. Thus, a rhodamine dye with superior pH sensitivity and high thermal stability was synthesized and incorporated in nylon 6 and polyester fabrics to fabricate textile sensors through dyeing and printing methods. The spectral properties and solubility of the dye were examined; sensitivity to acidic gas as well as durability and reversibility of the fabricated textile sensors were investigated. Both dyed and printed sensors exhibited a high reaction rate and distinctive color change under the acidic condition owing to the high pH sensitivity of the dye. In addition, both sensors have outstanding durability and reversibility after washing and drying.
ABSTRACT
Three strains of Pseudomonas aeruginosa were isolated: wild-type (WT, NO4) showed normal quorum sensing (QS), whereas QSD3 and QSD7 were QS-deficient (QSD) containing limited N-butyryl homoserine lactone (C4-HSL). The autoinducer activity produced by NO4 was found to be at least 50-fold higher than those by the QSD3 and the QSD7 strains. The QSDs produced lower levels of phenazine compounds (pyocyanin), siderophores (pyoverdine) and biosurfactants (rhamnolipids) than NO4. Therefore, the swarming motility and the swimming motility of the QSD3 and the QSD7 strains also decreased. Treatment with exogenous C4-HSL completely restored rhamnolipid production in both QSDs, suggesting that the biosynthesis of C4-HSL is defective. However, the biofilm production of the QSDs reached much higher levels than those of wild-types (NO4 and P. aeruginosa PAO1). And both QSD strains were more resistant than wild-type cell (NO4) against kanamycin and tobramycin. The RpoS gene, which function is related with QS, is point-nonsense mutated in QSD3 strain. But eleven QS-related genes in QSD3 were not mutated, compared to those of PAO1, which carries intact QS genes and is used as a positive control. This study is helpful in the development of novel approaches in the treatment of P. aeruginosa infections.
Subject(s)
Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/metabolism , Quorum Sensing/genetics , Quorum Sensing/physiology , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/physiology , Biofilms/growth & development , DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial , Gene Expression Regulation, Bacterial , Genes, Bacterial/genetics , Glycolipids/metabolism , Kanamycin/pharmacology , Oligopeptides/metabolism , Pseudomonas Infections , Pseudomonas aeruginosa/drug effects , Pyocyanine/metabolism , Sequence Analysis , Sequence Analysis, DNA , Sigma Factor/genetics , Sigma Factor/physiology , Tobramycin/pharmacology , Virulence Factors/geneticsABSTRACT
Purpose: Cancer cells grow in an unfavorable metabolic milieu in the tumor microenvironment and are constantly exposed to metabolic stress such as chronic nutrient depletion. Cancer stem-like cells (CSC) are intrinsically resistant to metabolic stress, thereby surviving nutrient insufficiency and driving more malignant tumor progression. In this study, we aimed to demonstrate the potential mechanisms by which CSCs avoid Ca2+-dependent apoptosis during glucose deprivation.Experimental Design: We investigated cell viability and apoptosis under glucose deprivation, performed genome-wide transcriptional profiling of paired CSCs and parental cells, studied the effect of calcium/calmodulin-dependent protein kinase 2 alpha (CaMK2α) gene knockdown, and investigated the role of nuclear factor kappa B (NFκB) in CSCs during time-dependent Ca2+-mediated and glucose deprivation-induced apoptosis. We also observed the effect of combined treatment with 2-deoxy-d-glucose, a metabolic inhibitor that mimics glucose deprivation conditions in mouse xenograft models, and thapsigargin, a specific inhibitor of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA).Results: We demonstrated the coordinated upregulation of SERCA in CSCs. SERCA, in turn, is transcriptionally regulated by CaMK2α via NFκB activation. Combined treatment with 2-deoxy-d-glucose and thapsigargin, a specific inhibitor of SERCA, significantly reduced tumor growth compared with that in untreated control animals or those treated with the metabolic inhibitor alone.Conclusions: The current study provides compelling evidence that CaMK2α acts as a key antiapoptosis regulator in metabolic stress-resistant CSCs by activating NFκB. The latter induces expression of SERCA, allowing survival in glucose-deprived conditions. Importantly, our combination therapeutic strategy provides a novel approach for the clinical application of CSC treatment. Clin Cancer Res; 24(7); 1677-90. ©2017 AACR.
Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium-Transporting ATPases/metabolism , Calcium/metabolism , Endoplasmic Reticulum/metabolism , Neoplastic Stem Cells/metabolism , Stress, Physiological/physiology , Up-Regulation/physiology , Animals , Apoptosis/drug effects , Apoptosis/physiology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/physiology , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum Stress/physiology , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , NF-kappa B/metabolism , Neoplastic Stem Cells/drug effects , Signal Transduction/drug effects , Signal Transduction/physiology , Stress, Physiological/drug effects , Thapsigargin/pharmacology , Transcriptional Activation/drug effects , Transcriptional Activation/physiology , Up-Regulation/drug effectsABSTRACT
Seeds of Carthamus tinctorius L. (Compositae) have been used in Korean traditional medicines for the treatment of cardiovascular and bone diseases. In this study, we investigated the anti-inflammatory effects of known serotonin derivatives (1-9) isolated from the ethyl acetate (EtOAc) soluble fraction from the seeds of C. tinctorius. Compound 2, identified as moschamine, most potently inhibited lipopolysaccharide (LPS)-induced production of prostaglandin E2 (PGE2) and nitric oxide (NO) in RAW 264.7 macrophages. Moschamine concentration-dependently inhibited LPS-induced PGE2 and NO production in RAW 264.7 macrophages. Consistent with these findings, moschamine suppressed the protein and mRNA levels of cyclooxygenase-2 (COX-2), microsomal prostaglandin E2 synthase (mPGES)-1, and inducible NO synthase (iNOS), interleukin (IL)-6, and IL-1ß. In addition, pretreatment of moschamine significantly inhibited LPS-stimulated the transcriptional activity of activator protein-1 (AP-1) and the phosphorylation of signal transducer and activator of transcription (STAT)1/3 in RAW 264.7 macrophages. Moreover, moschamine inhibited LPS-induced the phosphorylation of p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinase (ERK), but it had no effect on c-Jun N-terminal kinase (JNK). These results suggest that the mechanism of anti-inflammatory activity of moschamine is associated with the downregulation of COX-2, mPGES-1, iNOS, IL-6, and IL-1ß expression through the suppression of AP-1 and STAT1/3 activation in LPS-induced RAW 264.7 macrophages.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carthamus tinctorius/chemistry , Inflammation Mediators/antagonists & inhibitors , Lipopolysaccharides/antagonists & inhibitors , Macrophages/drug effects , Serotonin/analogs & derivatives , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Dose-Response Relationship, Drug , Inflammation Mediators/pharmacology , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Mice , Molecular Structure , RAW 264.7 Cells , STAT1 Transcription Factor/antagonists & inhibitors , STAT1 Transcription Factor/metabolism , STAT3 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/metabolism , Serotonin/chemistry , Serotonin/isolation & purification , Serotonin/pharmacology , Structure-Activity Relationship , Transcription Factor AP-1/antagonists & inhibitors , Transcription Factor AP-1/metabolismABSTRACT
BACKGROUND: The purpose of this study was to analyze the characteristics of cracked teeth and to evaluate pulp status according to periodontal probing depth (PPD). METHODS: A total of 182 cracked teeth were included. The location and type of the cracked teeth, age and gender of the patients, restoration type, pulp status, PPD, and radiographic findings were analyzed. RESULTS: Mandibular second molars (25.3%) were the most frequently involved teeth, followed by mandibular first molars (22.5%), maxillary first molars (22.0%), and maxillary second molars (17.6%). The patient age was most frequently 50-59 years. Cracks occurred mainly in nonbonded restorations, such as gold (26.9%), and were usually found in intact teeth (37.9%). A total of 103 teeth (56.6%) had an initial PPD of less than 3 mm, while 40 (22.0%) had a PPD of 4-6 mm, and 39 (21.4%) had PPD of 7 mm or more. A total of 33 cracked teeth (18.1%) were diagnosed with pulp necrosis, 40 (22.0%) with irreversible pulpitis, and 97 (53.3%) with reversible pulpitis. The incidence of pulp necrosis was 31.8% among cracked teeth with a PPD of 4-6 mm, and 28.6% among those with a PPD of 7 mm or more. CONCLUSIONS: Cracks occurred mainly in molar teeth, and were commonly found in intact teeth with no restoration. Patients with cracked teeth were most frequently aged 50-59 years. Cracked teeth showing a PPD of more than 4 mm were more likely to show pulp necrosis.
Subject(s)
Cracked Tooth Syndrome/epidemiology , Dental Pulp Necrosis/diagnosis , Pulpitis/diagnosis , Adult , Age Distribution , Aged , Cracked Tooth Syndrome/diagnosis , Dental Pulp/diagnostic imaging , Dental Restoration, Permanent/adverse effects , Female , Humans , Male , Middle Aged , Periodontal Index , Radiography, Dental , Young AdultABSTRACT
OBJECTIVE: The aim of this study was to investigate the three-dimensional (3D) position of the center of resistance of 4 mandibular anterior teeth, 6 mandibular anterior teeth, and the complete mandibular dentition by using 3D finite-element analysis. METHODS: Finite-element models included the complete mandibular dentition, periodontal ligament, and alveolar bone. The crowns of teeth in each group were fixed with buccal and lingual arch wires and lingual splint wires to minimize individual tooth movement and to evenly disperse the forces onto the teeth. Each group of teeth was subdivided into 0.5-mm intervals horizontally and vertically, and a force of 200 g was applied on each group. The center of resistance was defined as the point where the applied force induced parallel movement. RESULTS: The center of resistance of the 4 mandibular anterior teeth group was 13.0 mm apical and 6.0 mm posterior, that of the 6 mandibular anterior teeth group was 13.5 mm apical and 8.5 mm posterior, and that of the complete mandibular dentition group was 13.5 mm apical and 25.0 mm posterior to the incisal edge of the mandibular central incisors. CONCLUSIONS: Finite-element analysis was useful in determining the 3D position of the center of resistance of the 4 mandibular anterior teeth group, 6 mandibular anterior teeth group, and complete mandibular dentition group.
ABSTRACT
The inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays important roles in prevention and treatment of Alzheimer's disease (AD). Among the individual parts of Morus alba L. including root bark, branches, leaves, and fruits, the root bark showed the most potent enzyme inhibitory activities. Therefore, the aim of this study was to evaluate the anti-AD activity of the M. alba root bark and its isolate compounds, including mulberrofuran G (1), albanol B (2), and kuwanon G (3) via inhibition of AChE, BChE, and BACE1. Compounds 1 and 2 showed strong AChE- and BChE-inhibitory activities; 1-3 showed significant BACE1 inhibitory activity. Based on the kinetic study with AChE and BChE, 2 and 3 showed noncompetitive-type inhibition; 1 showed mixed-type inhibition. Moreover, 1-3 showed mixed-type inhibition against BACE1. The molecular docking simulations of 1-3 demonstrated negative binding energies, indicating a high affinity to AChE and BACE1. The hydroxyl group of 1-3 formed hydrogen bond with the amino acid residues located at AChE and BACE1. Consequently, these results indicate that the root bark of M. alba and its active compounds might be promising candidates for preventive and therapeutic agents for AD.
Subject(s)
Alzheimer Disease/drug therapy , Morus/chemistry , Plant Bark/chemistry , Plant Roots/chemistry , Amino Acids/chemistry , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/biosynthesis , Aspartic Acid Endopeptidases/antagonists & inhibitors , Aspartic Acid Endopeptidases/biosynthesis , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/pharmacology , Hydrogen Bonding , Kinetics , Models, Molecular , Molecular Docking Simulation , Plant Extracts/chemistry , Plant Extracts/pharmacologyABSTRACT
BACKGROUND: Nonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD) event in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: Laboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events. RESULTS: Nonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR) and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m², and albuminuria. CONCLUSION: The results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.
ABSTRACT
Sweet potato Daeyumi starch was dually modified using glycogen branching enzyme (BE) from Streptococcus mutans and amylosucrase (AS) from Neisseria polysaccharea to prepare slowly digestible starch (SDS). Dually modified starches had higher SDS and resistant starch (RS) contents than control starch. The branched chain length distributions of the BE-modified starches indicated an increase in short side-chains [degree of polymerization (DP)≤12] compared with native starch. AS treatment of the BE-modified starches decreased the proportion of short side-chains and increased the proportion of long side-chains (DP≥25) and molecular mass. It also resulted in a B-type X-ray diffraction pattern and an increased relative crystallinity. Regarding thermal properties, the BE-modified starches showed no endothermic peak, whereas the BEAS-modified starches had a broader melting temperature range and lower melting enthalpy compared to native starch. The combined enzymatic treatment resulted in novel glucan polymers with slow digestion properties.
Subject(s)
1,4-alpha-Glucan Branching Enzyme/metabolism , Amylopectin/metabolism , Glucosyltransferases/metabolism , Ipomoea batatas/chemistry , Amylopectin/chemistry , Amylopectin/isolation & purification , Animals , Digestion , Neisseria , Pancreatin/metabolism , Streptococcus mutans , Swine , Temperature , ThermodynamicsABSTRACT
BACKGROUND: Vitamin-mineral supplements are the most popular dietary supplements in Korea. However, few studies have assessed the relationship between vitamin-mineral supplementation and associated factors among the Korean elderly. The purpose of this study was to assess the use of vitamin-mineral supplements among elderly in Korea as well as its association with sociodemographic factors, health-related behaviors, medical conditions, and nutrient intake. METHODS: This study was based on data from the Korean National Health and Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare from 2008 to 2009. Data from 3,294 elderly men and women (65 years of age and older) were analyzed. Multivariable-weighted logistic regression model analysis was used to evaluate the association between vitamin-mineral supplement use and sociodemographic factors, health-related habits, and medical conditions. RESULTS: Vitamin-mineral supplementation was reported by 16.3% of the participants. The most common reason for using dietary supplements was recommendations from friends and acquaintances. Highly educated person, female participants had a greater likelihood of taking vitamin-mineral supplements. In addition, analysis of nutrient intake from food sources alone revealed a lower proportion of vitamin-mineral supplement users with nutrient intakes below the estimated average requirements for vitamin A, vitamin C, thiamine, riboflavin, niacin, calcium, iron, and phosphorus, compared to nonusers. However, vitamin-mineral supplementation was not associated with health-related behaviors or medical conditions. CONCLUSION: Highly educated person, elderly Korean women had a greater likelihood of using vitamin-mineral supplements. In addition, nutrient intakes from food sources alone were significantly higher among vitamin-mineral supplement users. Finally, vitamin-mineral supplementation may be an indicator of healthier diet in elderly Koreans.
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PURPOSE: This research aims to investigate the potential of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) to predict pathologic response after neoadjuvant chemotherapy (NAC) and overall survival (OS) of patients with synovial sarcoma in Korea. METHODS: Twenty patients with synovial sarcoma from January 2001 to December 2011 were reviewed retrospectively. All patients underwent pre-treatment FDG PET and tumor removal. Patients were classified with the maximum SUV (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), age, sex, histologic subtype, tumor size, NAC, resection margin, and metastasis at diagnosis. Pathologic response was assessed using the French Federation of Cancer Centers system. Statistical analyses were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards regression model, and Mann-Whitney test. RESULTS: Nine patients (45 %) showed pathologic response, and ten patients survived. Higher SUVmax, higher MTV, higher TLG, monophasic epithelial type, and metastasis at diagnosis were significantly related to poorer OS (p = 0.047, 0.016, 0.016, 0.045, and 0.018, respectively). By multivariate analysis, metastasis at diagnosis was significantly related to poorer OS (p = 0.012/HR = 5.9, 95 % CI 1.47 to 24.1). The SUVmax, MTV, and TLG of the non-responder group were significantly higher than those of the responder group (p = 0.020, 0.020, and 0.020, respectively). There was no significant difference in size between the two groups (p = 0.062). CONCLUSIONS: A higher SUVmax on the pre-treatment scan, monophasic epithelial type, and metastasis at diagnosis were significantly associated with a poorer OS, and pathologic responders showed a higher SUVmax before NAC. The PET parameters can be used to predict OS and pathologic response in patients with synovial sarcomas before NAC.
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BACKGROUND: Epigenetic modifications play a critical role in the regulation of all DNA-based processes, such as transcription, repair, and replication. Inappropriate histone modifications can result in dysregulation of cell growth, leading to neoplastic transformation and cell death. Renal tumors have been shown to have a higher global methylation percentage and reduced histone acetylation. Preclinical models have revealed that histone gene modifiers and epigenetic alterations play important roles in renal cell carcinoma (RCC) tumorigenesis. Recently, a novel HDAC inhibitor, N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), has been introduced as an example of a new class of anti-cancer agents. The anti-cancer activity of HNHA and the underlying mechanisms of action remain to be clarified. METHODS: The MTS assay using a panel of RCC cells was used to evaluate the anti-proliferative effects of HNHA. The established HDAC inhibitors, SAHA and TSA, were used for comparison. Western blotting analysis was performed to investigate the acetylation of histone H3 and the expression of apoptotic markers in vitro and in vivo. Subcellular fractionation was performed to evaluate expression of Bax and cytochrome c in the cytosol and mitochondria, and also translocation of cytochrome c from the cytoplasm to the nucleus. A confocal microscopic evaluation was performed to confirm inhibition of cell proliferation, induction of apoptosis, and the nuclear translocation of cytochrome c in RCC cells. RESULTS: In this study, we investigated the apoptosis-inducing activity of HNHA in cultured kidney cancer cells. Apoptosis in the HNHA-treated group was induced significantly, with marked caspase activation and Bcl-2 suppression in RCC cells in vitro and in vivo. HNHA treatment caused cytochrome c release from mitochondria, which was mediated by increased Bax expression and caspase activation. HNHA also induced nuclear translocation of cytochrome c, suggesting that HNHA can induce caspase-independent nuclear apoptosis in RCC cells. An in vivo study showed that HNHA had greater anti-tumor and pro-apoptotic effects on RCC xenografts than the established HDAC inhibitors. CONCLUSIONS: HNHA has more potent anti-tumor activity than established HDAC inhibitors. Its activities are mediated by caspase-dependent and cytochrome-c-mediated apoptosis in RCC cells. These results suggest that HNHA may offer a new therapeutic approach to RCC.
Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Carcinoma, Renal Cell/drug therapy , Cytochromes c/metabolism , Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/therapeutic use , Kidney Neoplasms/drug therapy , Naphthalenes/therapeutic use , Acetylation , Animals , Blotting, Western/methods , Carcinoma, Renal Cell/enzymology , Carcinoma, Renal Cell/pathology , Caspases/metabolism , Cell Fractionation/methods , Histones/metabolism , Humans , I-kappa B Proteins/metabolism , In Situ Nick-End Labeling , Kidney Neoplasms/enzymology , Kidney Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Mitochondria/enzymology , Neoplasm Transplantation , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Cells, Cultured , bcl-2-Associated X Protein/metabolismABSTRACT
BACKGROUND/AIMS: The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. METHODS: Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 ± 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 µg/kg/min). RESULTS: Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 µg/kg/min and showed a dyssynchronous pattern at 20 µg/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 µg/kg/min challenge, radial strain and displacement of anterior segments at 20 µg/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 ± 14.9% vs. 78.4 ± 20.1% and 5.3 ± 2.3 mm vs. 8.5 ± 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. CONCLUSIONS: Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB.
Subject(s)
Adrenergic beta-1 Receptor Agonists , Dobutamine , Echocardiography, Stress/methods , Myocardial Contraction , Myocardium , Ventricular Dysfunction, Left , Ventricular Function, Left/drug effects , Adult , Aged , Chest Pain , Coronary Angiography , Diastole , Echocardiography, Stress/instrumentation , Female , Humans , Male , Middle Aged , Physical Exertion , SystoleABSTRACT
Cholesterol granuloma is a histological term used for the description of a tissue response to a foreign body such as cholesterol crystals. Cholesterol granuloma is histologically characterized as fibrous granulation tissue containing cholesterol crystals within surrounding giant cells. Cases of cholesterol granuloma of the pancreas are very rare. We report a case of a 47-year old male who had a cholesterol granuloma of the pancreas. Abdominal CT showed 24 mm-sized cyst in the pancreas and peri-pancreatic regional mass infiltrating to the stomach. PET-CT revealed increased 18F-FDG uptake at the cyst and peri-pancreatic mass. Thus, Whipple's operation was done. The disease was confirmed by surgical pathologic examination of the tissue. Pathologic examination of resected specimen showed numerous cholesterol crystals surrounded by multinucleated foreign body giant cells. We report on this case and give a brief review of the literature.