Ultraviolet B (UVB; 290~320nm) irradiation-induced lipid peroxidation induces inflammatory responses that lead to skin wrinkle formation and epidermal thickening. Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have the potential to be used as anti-wrinkle agents because they inhibit inflammatory response and lipid peroxidation. In this study, we evaluated the function of 2-bromo-4-(5-chloro-benzo[d]thiazol-2-yl) phenol (MHY 966), a novel synthetic PPAR α/γ dual agonist, and investigated its anti-inflammatory and anti-lipid peroxidation effects. The action of MHY 966 as a PPAR α/γ dual agonist was also determined in vitro by reporter gene assay. Additionally, 8-week-old melanin-possessing hairless mice 2 (HRM2) were exposed to 150 mJ/cm2 UVB every other day for 17 days and MHY 966 was simultaneously pre-treated every day for 17 days to investigate the molecular mechanisms involved. MHY 966 was found to stimulate the transcriptional activities of both PPAR α and γ. In HRM2 mice, we found that the skins of mice exposed to UVB showed significantly increased pro-inflammatory mediator levels (NF-κB, iNOS, and COX-2) and increased lipid peroxidation, whereas MHY 966 co-treatment down-regulated these effects of UVB by activating PPAR α and γ. Thus, the present study shows that MHY 966 exhibits beneficial effects on inflammatory responses and lipid peroxidation by simultaneously activating PPAR α and γ. The major finding of this study is that MHY 966 demonstrates potential as an agent against wrinkle formation associated with chronic UVB exposure.
For graphene to be used in semiconductor applications, a ‘wide energy gap' of at least 0.5 eV at the Dirac energy must be opened without the introduction of atomic defects. However, such a wide energy gap has not been realized in graphene, except in the cases of narrow, chemically terminated graphene nanostructures with inevitable edge defects. Here, we demonstrated that a wide energy gap of 0.74 eV, which is larger than that of germanium, could be opened in uniform monolayer graphene without the introduction of atomic defects into graphene. The wide energy gap was opened through the adsorption of self-assembled twisted sodium nanostrips. Furthermore, the energy gap was reversibly controllable through the alternate adsorption of sodium and oxygen. The opening of such a wide energy gap with minimal degradation of mobility could improve the applicability of graphene in semiconductor devices, which would result in a major advancement in graphene technology.
Appendicitis is the most common acute surgical emergency of childhood. Since the original report by Puylaert in 1986, the use of ultrasonography in the diagnosis of appendicitis has been the subject of considerable study. Among the reported diagnostic criteria, the maximal outer diameter (MOD) of the appendix is accepted as the one of the most reliable criteria used to differentiate between a normal appendix and acute appendicitis. However, MOD measurement is subject to inaccuracies because luminal distention by non-compressible, non-inflammatory material such as fecal material, or increased maximal mural thickness due to reactive mucosal lymphoid hyperplasia, or a medical cause due to a generalized gastrointestinal disease, such as Crohn’s disease, can cause the measurement to exceed the upper limits of normality. The aim of this article is to introduce the spectrum of ultrasonographic findings in the normal and abnormal appendix and eventually to reduce unnecessary surgery in children.
Acute appendicitis; Appendix; Children; Ultrasonography
Canine NK cells still are not well-characterized due to the lack of information concerning specific NK cell markers and the fact that NK cells are not an abundant cell population. In this study, we selectively expanded the canine cytotoxic large granular lymphocytes (CLGLs) that exhibit morphologic, genetic, and functional characteristics of NK cells from normal donor PBMCs. The cultured CLGLs were characterized by a high proportion of CD5(dim) expressing cells, of which the majority of cells co-expressed CD3 and CD8, but did not express TCRαβ and TCRγδ. The phenotype of the majority of the CLGLs was CD5(dim)CD3+CD8+ TCRαβ−TCRγδ−CD4−CD21−CD11c+/−CD11d+/−CD44+. The expression of mRNAs for NK cell-associated receptors (NKG2D, NKp30, NKp44, Ly49, perforin, and granzyme B) were highly upregulated in cultured CLGLs. Specifically, NKp46 was remarkably upregulated in the cultured CLGLs compared to PBMCs. The mRNAs for the NKT-associated iTCRα gene in CLGLs was present at a basal level. The cytotoxic activity of the CLGLs against canine NK cell-sensitive CTAC cells was remarkably elevated in a dose-dependent manner, and the CLGLs produced large amounts of IFN-γ. The antitumor activity of CLGLs extended to different types of canine tumor cells (CF41.Mg and K9TCC-pu-AXC) without specific antigen recognition. These results are consistent with prior reports, and strongly suggest that the selectively expanded CLGLs represent a population of canine NK cells. The results of this study will contribute to future research on canine NK cells as well as NK cell-based immunotherapy.
Canine; Cytotoxic large granular lymphocytes; NK cells; Expansion; Cytotoxicity
The proteasome is a key regulator of cellular protein homeostasis and is a clinically validated anticancer target. The immunoproteasome, a subtype of proteasome expressed mainly in hematopoietic cells, was initially recognized for its role in antigen presentation during the immune response. Recently, the immunoproteasome has been implicated in several disease conditions including cancer and autoimmune disorders, but many of the factors contributing to these pathological processes remain unknown. In particular, the codon 60 polymorphism of the PSMB9 gene encoding the β1i immunoproteasome catalytic subunit has been investigated in the context of a variety of diseases. Despite this, previous studies have so far reported inconsistent findings regarding the impact of this polymorphism on proteasome activity. Thus, we set out to investigate the impact of the PSMB9 codon 60 polymorphism on the expression and activity of the β1i immunoproteasome subunit in a panel of human cancer cell lines. The β1i-selective fluorogenic substrate Acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin was used to specifically measure β1i catalytic activity. Our results indicate that the codon 60 Arg/His polymorphism does not significantly alter the expression and activity of β1i among the cell lines tested. Additionally, we also examined the expression of β1i in clinical samples from colon and pancreatic cancer patients. Our immunohistochemical analyses showed that ∼70% of clinical colon cancer samples and ∼53% of pancreatic cancer samples have detectable β1i expression. Taken together, our results indicate that the β1i subunit of the immunoproteasome is frequently expressed in colon and pancreatic cancers but that the codon 60 genetic variants of β1i display similar catalytic activities and are unlikely to contribute to the significant inter-cell-line and inter-individual variabilities in the immunoproteasome activity.
The manifestation of infective endocarditis often resembles vasculitis. Approximately one in five infective endocarditis cases are referred initially to a nephrologist because of abnormal renal function or abnormal urinalysis; therefore, infection should be ruled out before diagnosing vasculitis.
A case involving a patient with infective endocarditis who presented with migrating skin lesions, renal infarction and multiple pseudoaneurysms is reported. Echocardiography revealed mitral valve vegetation and viridans streptococci were identified in peripheral blood cultures. Although mitral valve annuloplasty and an aneurysm ligation operation were performed with proper antibiotic treatment, the remaining mycotic aneurysm progressed and caused neurological complications. The patient was cured completely after reoperation.
Aneurysm; Endocarditis; Infected; Vasculitis
The goal of this study is to compare the overall quality of film mammograms taken according to the Korean standards with the American College of Radiology (ACR) standard for clinical image evaluation and to identify means of improving mammography quality in Korea.
Materials and Methods
Four hundred and sixty eight sets of film mammograms were evaluated with respect to the Korean and ACR standards for clinical image evaluation. The pass and failure rates of mammograms were compared by medical facility types. Average scores in each category of the two standards were evaluated. Receiver operating characteristic curve analysis was used to identify an optimal Korean standard pass mark by taking the ACR standard as the reference standard.
93.6% (438/468) of mammograms passed the Korean standard, whereas only 80.1% (375/468) passed the ACR standard (p < 0.001). Non-radiologic private clinics had the lowest pass rate (88.1%: Korean standard, 71.8%: ACR standard) and the lowest total score (76.0) by the Korean standard. Average scores of positioning were lowest (19.3/29 by the Korean standard and 3.7/5 by the ACR standard). A cutoff score of 77.0 for the Korean standard was found to correspond to a pass level when the ACR standard was applied.
We suggest that tighter regulations, such as, raising the Korean pass mark, subtracting more for severe deficiencies, or considering a very low scores in even a single category as failure, are needed to improve the quality of mammography in Korea.
Mammography; Quality assurance; Accreditation; Breast
Helicobacter pylori infection induces cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) overexpression, and these factors may engage in cross-talk. The aim of the present study was to evaluate the effect of H. pylori on EGFR signaling pathways and to determine whether celecoxib has an inhibitory effect on this pathway.
The AGS cell line was cocultured with H. pylori G27 and the isogenic cagE- mutant. The expression of COX-2, EGFR, heparin binding-epidermal growth factor (HB-EGF), and transforming growth factor-β (TGF-β) was measured by real time-polymerase chain reaction (RT-PCR). Next, Western blot analyses of COX-2, EGFR, total Akt, phosphorylated Akt (pAkt), and phosphorylated glycogen synthase kinase-3β (pGSK3β) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 µmol/L).
H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-β, as detected by RT-PCR. However, AGS cells treated with cagE- mutants, which have a defective type IV secretion system, did not exhibit EGFR upregulation. Celecoxib had inhibitory effects on the H. pylori-induced overexpression of COX-2 (p=0.015), EGFR (p=0.025), pAkt (p=0.025), and pGSK3β (p=0.029) by Western blot analysis.
H. pylori with an intact type IV secretion system activated the COX-2 and EGFR-Akt pathways in the AGS cell line. As celecoxib exhibited inhibitory effects on the EGFR signaling pathway, the cross-talk of COX-2 and EGFR likely mediates H. pylori-induced gastric cancer.
Gastric carcinoma; Helicobacter pylori; Cyclooxygenase 2; Receptor, epidermal growth factor; Celecoxib
Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to assess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat.
Acid secretions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, respectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H+-K+-ATPase were determined. The area of connective tissue of lamina propria was measured.
Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H+-K+-ATPase significantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of connective tissue.
As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to comparable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach.
Gastric acid; Hydrogen-potassium-activated ATPase; Cochinchina momordica seed; Aging; Connective tissue
There are no reports regarding pneumomediastinum caused by thoracic epidural block complications. We believe that it is possible to experience an occurrence of pneumomediastinum caused by air in the epidural space after performing a thoracic epidural block using the loss of resistance (LOR) technique with air. We report a witnessed case where pneumomediastinum appeared after a thoracic epidural block. Pneumorrrhachis, paravertebral muscle emphysema, and pneumomediastinum were diagnosed by Positron Emission Tomography-Computed Tomography. Although extremely rare, pneumomediastinum can be caused by an epidural block using LOR technique with air. In order to avoid the above danger, the use of saline or very minimal amount of air is required during a careful LOR technique.
Emphysema; Epidural injection; Pneumomediastinum
A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia.
Though the effects of acupuncture in atopic dermatitis have been proven in clinical studies, its mechanism remains unclear. In this study, we investigate the effectiveness and mechanism of action for acupuncture treatment on the LI11 meridian point for treatment of allergic contact dermatitis. BALB/c mice received 1-chloro-2,4-dinitrobenzene (DNCB) application to induce skin inflammation. Acupuncture treatment on LI11 significantly inhibited cutaneous hyperplasia, serum IgE levels, and expression of proinflammatory cytokine (IL-4, IL-8, and TNF-α) mRNA and NF-κB, ERK1/2, JNK, and p38 proteins. Acupuncture treatment of local points also inhibited cutaneous hyperplasia and serum IgE levels; however, it was not effective in regulating proinflammatory cytokines and proteins. In addition, LI11 treatment is more effective at reducing serum IgE levels and pro-inflammatory cytokines and proteins than local point treatment. These results suggest that acupuncture treatment is effective in alleviating allergic contact dermatitis by reducing pro-inflammatory cytokines and proteins.
To determine the association of regular exercise, BMI, and fasting glucose with the risk of type 2 diabetes and to predict the risk.
RESEARCH DESIGN AND METHODS
Korean subjects (n = 7,233; 40–79 years old) who were not diagnosed with diabetes at baseline were enrolled through the National Health Insurance Corporation. All participants underwent biennial examinations, and 1,947 of 7,233 subjects also underwent a 6-month program of moderate-intensity exercise (300 min/week) without dietary advice.
During follow-up (mean = 2 years), there were 303 incidents of type 2 diabetes in the nonexercise program group (n = 5,286) and 83 in the exercise program group (n = 1,947). After adjusting for confounders, the risk of type 2 diabetes was positively associated with BMI and inversely with regular exercise, especially among overweight/obese subjects. After further adjustment for BMI, the odds ratios for risk of diabetes associated without and with regular exercise were 1.00 and 0.77, respectively. Among subjects with normal fasting glucose, exercise reduced the diabetes risk; however, among those with impaired fasting glucose (IFG), the protective effect of exercise was found only among overweight/obese subjects. The overweight/obese subjects in the exercise program group exhibited improved fasting glucose compared with the nonexercise program group and showed 1.5 kg of weight loss and a 3-cm decrease in waist circumference. Among overweight/obese subjects with unchanged fasting glucose, weight loss was greater in the exercise program group.
Regular exercise reduces the risk of type 2 diabetes in overweight/obese individuals. Particularly, regular exercise and weight or waist circumference control are critical factors for preventing diabetes in overweight/obese individuals with IFG.
Alternative cleavage and polyadenylation (APA) leads to mRNA isoforms with different coding sequences (CDS) and/or 3′ untranslated regions (3′UTRs). Using 3′ Region Extraction And Deep Sequencing (3′READS), a method which addresses the internal priming and oligo(A) tail issues that commonly plague polyA site (pA) identification, we comprehensively mapped pAs in the mouse genome, thoroughly annotating 3′ ends of genes and revealing over five thousand pAs (~8% of total) flanked by A-rich sequences, which have hitherto been overlooked. About 79% of mRNA genes and 66% of long non-coding RNA (lncRNA) genes have APA; but these two gene types have distinct usage patterns for pAs in introns and upstream exons. Promoter-distal pAs become relatively more abundant during embryonic development and cell differentiation, a trend affecting pAs in both 3′-most exons and upstream regions. Upregulated isoforms generally have stronger pAs, suggesting global modulation of the 3′ end processing activity in development and differentiation.
cleavage and polyadenylation; splicing; mouse; mRNA; lncRNA; development; differentiation
Xanthium stramarium (XAS) and Psoralea corylifolia (PSC), phototoxic oriental medicinal plants, has been used in traditional medicines in Asian countries.
The effects of highly purified XAS or PSC extract combined with ultraviolet A1 (UVA1) irradiation on cell proliferation and transforming growth factor-beta1 (TGF-β1) expression of the keloid fibroblast were being investigated to define potential therapeutic uses for keloid treatments.
The keloid fibroblasts were treated with XAS or PSC alone or in the combination with UVA1 irradiation. The cell viability, apoptosis, and expression of TGF-β1 and collagen I were investigated.
XAS and PSC in combination with UVA1 irradiation suppressed cell proliferation and induced apoptosis of keloid fibroblasts. Furthermore, the XAS and PSC in combination with UVA1 irradiation inhibited TGF-β1 expression and collagen synthesis in keloid fibroblasts.
These findings may open up the possibility of clinically used XAS or PSC in combination with UVA1 irradiation for keloid treatments.
Apoptosis; Keloid; Psoralea corylifolia; Transforming growth factor-beta 1; Xanthium stramarium
Topical photodynamic therapy (PDT) has been increasingly used to treat malignant skin tumors including the Bowen disease. However, patients could be displeased with the long incubation time required for conventional PDT.
We evaluated the efficacy and safety of PDT with a short incubation time of ablative CO2 fractional laser pretreatment for treating Bowen disease.
Ten patients were included. Just before applying the topical photosensitizer, all lesions were treated with ablative CO2 fractional laser, following the application of methyl aminolevulinate and irradiation with red light (Aktilite CL 128). Histological confirmation, rebiopsy, and clinical assessments were performed. Adverse events were also recorded.
Five of the ten (50%) lesions showed a complete response (CR) within three PDT sessions. After four treatment sessions, all lesions except one penile shaft lesion (90%) achieved clinical and histological CR or clinical CR only. The average number of treatments to CR was 3.70±1.70. The treatments showed favorable cosmetic outcomes and no serious adverse events.
The results suggest that pretreatment with an ablative fractional CO2 laser before PDT has similar treatment efficacy and requires a shorter photosensitizer incubation time compared with the conventional PDT method.
Ablative carbon dioxide fractional laser; Bowen disease; Photodynamic therapy; Pretreatment
The aim of this study was to compare the passivity of implant superstructures by assessing the strain development around the internal tapered connection implants with strain gauges.
MATERIALS AND METHODS
A polyurethane resin block in which two implants were embedded served as a measurement model. Two groups of implant restorations utilized cement-retained design and internal surface of the first group was adjusted until premature contact between the restoration and the abutment completely disappeared. In the second group, only nodules detectable to the naked eye were removed. The third group employed screw-retained design and specimens were generated by computer-aided design/computer-aided manufacturing system (n=10). Four strain gauges were fixed on the measurement model mesially and distally to the implants. The strains developed in each strain gauge were recorded during fixation of specimens. To compare the difference among groups, repeated measures 2-factor analysis was performed at a level of significance of α=.05.
The absolute strain values were measured to analyze the magnitude of strain. The mean absolute strain value ranged from 29.53 to 412.94 µm/m at the different strain gauge locations. According to the result of overall comparison, the cement-retained prosthesis groups exhibited significant difference. No significant difference was detected between milled screw-retained prostheses group and cement-retained prosthesis groups.
Within the limitations of the study, it was concluded that the cement-retained designs do not always exhibit lower levels of stress than screw-retained designs. The internal adjustment of a cement-retained implant restoration is essential to achieve passive fit.
Implant prosthesis; Cement retention; Screw retention; Cement space; Passive fit; Strain gauge
There is currently considerable effort to incorporate both diagnostic and therapeutic functions into a single nanoscale system for the more effective treatment of cancer. Nanoparticles have great potential to achieve such dual functions, particularly if more than one type of nanostructure can be incorporated in a nanoassembly—referred to in this review as a hybrid nanoparticle. Here we review recent developments in the synthesis and evaluation of such hybrid nanoparticles based on two design strategies (barge vs. tanker), in which liposomal, micellar, porous silica, polymeric, viral, noble metal, and nanotube systems are incorporated either within (barge) or at the surface of (tanker) a nanoparticle. We highlight the design factors that should be considered to obtain effective nanodevices for cancer detection and treatment.
medical imaging; drug delivery; nanoparticles; targeting; superparamagnetic nanoparticles; micelles; porous silicon; mesoporous silica; liposomes; viral nanoparticles; nanotubes
Ninjurin1 is known as an adhesion molecule promoting leukocyte trafficking under inflammatory conditions. However, the posttranslational modifications of Ninjurin1 are poorly understood. Herein, we defined the proteolytic cleavage of Ninjurin1 and its functions. HEK293T cells overexpressing the C- or N-terminus tagging mouse Ninjurin1 plasmid produced additional cleaved forms of Ninjurin1 in the lysates or conditioned media (CM). Two custom-made anti-Ninjurin1 antibodies, Ab1–15 or Ab139–152, specific to the N- or C-terminal regions of Ninjurin1 revealed the presence of its shedding fragments in the mouse liver and kidney lysates. Furthermore, Matrix Metalloproteinase (MMP) 9 was responsible for Ninjurin1 cleavage between Leu56 and Leu57. Interestingly, the soluble N-terminal Ninjurin1 fragment has structural similarity with well-known chemokines. Indeed, the CM from HEK293T cells overexpressing the GFP-mNinj1 plasmid was able to attract Raw264.7 cells in trans-well assay. Collectively, we suggest that the N-terminal ectodomain of mouse Ninjurin1, which may act as a chemoattractant, is cleaved by MMP9.
Ninjurin1; Posttranslational modification; MMP9; Proteolytic cleavage; Chemotaxis
Keloids are often resistant to treatment and have high recurrence rates. To the best of the authors’ knowledge, however, there have been very few case reports related to foot keloids. The purpose of this retrospective case-series was to summarize the baseline characteristics of a cohort of patients, introduce our treatment regimen for the successful treatment of foot keloids.
Patients were treated with surgical excision followed by full thickness skin grafting combined with postoperative steroid injections combined with silicone gel sheeting over a period of eight years from December 2004 to November 2012 at our institution. Subjective outcome was evaluated using Patient Scar Assessment Scales. The final objective outcome was judged by two independent physicians at the time of 12 months after treatment as recurrence or non-recurrence.
Of 79 patients, 75 (94.9%) were women and 4 (5.1%) were men. The average age was 18 (range 7-43) years. The average pretreatment total size of the lesions was 50 (range 18-150) cm. The number of patients treated for a primary foot keloid was 29 (36.7%), and 70 patients (63.3%) were treated for a recurrent keloid that failed to respond to prior treatments. Prior treatments included single therapies such as surgical excision alone (4 patients, 5.1%), prior steroid injection alone (33 patients, 41.8%), and laser therapy (2 patients, 2.5%). Other therapies included combination treatments (11 patients, 13.9%). Most patients reported improved Patient Scar Assessment Scale by lapse of time. All patients completed the treatment regimen and follow-up of 12 months. Of these patients, 62 patients (78.5%) achieved successful treatment, while the remaining 17 (21.5%) experienced recurrence.
We successfully treated foot keloids using complete surgical excision and full thickness skin grafting followed by four corticosteroid injections (at one month intervals).
Keloid; Foot; Steroid; Recurrence
Heterozygous SCN5A mutations have been associated with varied arrhythmia phenotypes; phenotype severity may range from asymptomatic ECG changes (mild phenotype) to symptomatic arrhythmias resulting in syncope, cardiac arrest and sudden cardiac death (severe phenotype) even among family members carrying the same mutation. Risk-stratification schemes for SCN5A mutation carriers remain uncertain.
We used a family based approach to determine the role of SCN5A promoter variants and DNA methylation in predicting phenotype severity in a kindred with loss-of-function SCN5A mutation.
In a large kindred with a heterozygous SCN5A loss-of-function mutation (1936delC, Q646RfsX5; 22 mutation carriers), we sought SCN5A promoter variants. In addition, we assessed SCN5A and genome-wide DNA methylation profiles on genomic DNA derived from blood (Illumina Human Methylation27 BeadChip).
During systematic survey of 2.8kb SCN5A promoter region, we identified two SNPs in complete linkage disequilibrium (rs41310749 and rs41310239). These promoter variants were significantly associated with disease severity (mild vs. severe phenotype) (p=0.0007), as all three patients with severe phenotype carried the two-SNP variant on both mutant and wild-type alleles. Analysis did not support a role for methylation of SCN5A related genes.
These family-based genetic findings suggest that the presence of specific promoter variants increase the risk of a severe phenotype in heterozygous carriers of an SCN5A loss-of-function mutation.
Arrhythmia; Promoter; Genetic polymorphisms; Sudden cardiac death
Terminalia chebula is a native plant from southern Asia to southwestern China that is used in traditional medicine for the treatment of malignant tumors and diabetes. This plant also has antibacterial and immunomodulatory properties. The present study assessed T. chebula extract-dependent protein expression changes in Jurkat cells. Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry and Ingenuity Pathways Analysis (IPA) were performed to assess protein expression and networks, respectively. A comparative proteomic profile was determined in T. chebula extract (50 μg/mL)-treated and control cells; the expressions of β-tubulin, ring finger and CHY zinc finger domain containing 1, and insulin-like growth factor 1 receptor kinase were significantly down-regulated in T. chebula extract-treated Jurkat cells. Moreover, the molecular basis for the T. chebula extract-dependent protein expression changes in Jurkat cells was determined by IPA. Treatment with the T. chebula extract significantly inhibited nuclear factor-κB activity and affected the proteomic profile of Jurkat cells. The molecular network signatures and functional proteomics obtained in this study may facilitate the evaluation of potential antitumor therapeutic targets and elucidate the molecular mechanism of T. chebula extract-dependent effects in Jurkat cells.
gallic acid; Ingenuity Pathways Analysis; Jurkat cells; nuclear factor-κB; Terminalia chebula extract
The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review.
The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE.
Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence.
Differently from prior studies, our review included updated Norrköping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.
Prostatic neoplasm; Mass screening; Mortality; Prostate specific antigen; Review; Meta-analysis
We aimed to develop a quantitative enzyme-linked immunosorbent assay (ELISA) using whole-cell lysates of Helicobacter pylori 51 and to investigate its validity.
Data from 300 plates were obtained by two different operators. Standard sera were used to make a standard curve to analyze the quantity of anti-H. pylori immunoglobulin G (IgG) and IgA antibody. We obtained reproducible data with fewer dilutions of samples by the addition of serially diluted standard serum to each ELISA plate. To evaluate the validity of this ELISA, the 114 H. pylori-positive and -negative subjects were stratified into four age groups, i.e., 0 to 4, 5 to 9, 10 to 15, and 20 to 29 years, before testing.
The mean IgG-antibody titers in H. pylori-positive and -negative subjects were 1,766.4 IU/mL and 654.3 IU/mL (p<0.001). The mean IgA-antibody titers in H. pylori-positive and -negative subjects were 350.1 IU/mL and 193.5 IU/mL (p<0.001). Anti-H. pylori IgG and IgA titers in the four age groups were higher in H. pylori-positive subjects than in H. pylori-negative subjects (p<0.05).
Using the current ELISA based on whole-cell lysates of H. pylori 51, reliable anti-H. pylori antibody titers were obtained regardless of the subject's age.
Helicobacter pylori; Enzyme-linked immunosorbent assay; Antibodies