Atherosclerosis is a chronic and progressive inflammatory disease. Novel anti-inflammatory therapies may have promise as treatment strategies for cardiovascular risk reduction. Rosemary (Rosemarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory and antiatherosclerotic effects of rosemary need more study. This study investigated effects of the rosemary components, carnosic acid (CA), and carnosol (CAR), on cell migration. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) were determined by Western blot and gelatin zymography, respectively, in RAW 264.7 macrophages and vascular smooth muscle cells (VSMCs). VSMC migration was assessed by a Matrigel migration assay. Active compounds of rosemary extracts were also analyzed using a reversed-phase high-performance liquid chromatography. MMP-9 and MCP-1 activities were markedly diminished with methanol extract (RM), n-hexane fraction (RH), and CA in RAW 264.7 cells. RM, RH, CA, and CAR suppressed tumor necrosis factor-alpha–induced VSMC migration by inhibiting MMP-9 expression. Chromatograms of RM- and RH-containing CA and CAR revealed higher CA contents of RM (9.4%, 93.85 μg/mg dry wt.) and, especially, RH (18.4%, 184.00 μg/mg dry wt.), which were appreciably elevated compared with the similar CAR content in RM and RH (3.7%, 37.30 μg/mg dry wt.; and 2.5%, 25.05 μg/mg dry wt., respectively). Rosemary, especially its CA component, has potential antiatherosclerosis effects related to cell migration.
Rosemarinus officinalis L.; rosemary; matrix metalloproteinase-9 (MMP-9); monocyte chemoattractant protein-1 (MCP-1); migration; RAW 264.7 macrophages; vascular smooth muscle cell
The major cause of death in prostate cancer (PCa) cases is due to distant metastatic lesions, with the bone being the most prevalent site for secondary colonization. Utilization of small molecule inhibitors to treat bone metastatic PCa have had limited success either as monotherapies or in combination with other chemotherapeutics due to intolerable toxicities. In the current study, we developed a clinically relevant in vivo intraosseous tumor model overexpressing the platelet-derived growth factor D (PDGF D) to test the efficacy of a newly characterized VEGFR/PDGFR inhibitor, cediranib (also called AZD2171).
An intratibial-injection model was established utilizing DU145 cells without or with increased platelet-derived growth factor D (PDGF D) expression. Tumor-bearing mice were treated by daily gavage administration of cediranib and/or weekly i.p. injection of docetaxel for 7 weeks. Tibiae were monitored by in vivo/ex vivo x-rays and histomorphometry analysis was performed to estimate tumor volume and tumor-associated trabecular bone growth.
Cediranib reduced intraosseous growth of prostate tumors as well as tumor-associated bone responses. When compared to the standard chemotherapeutic agent docetaxel, cediranib exhibited a stronger inhibition of tumor-associated bone response. The efficacy of cediranib was further enhanced when the drug was co-administered with docetaxel. Importantly, the therapeutic benefits of cediranib and docetaxel are more prominent in intraosseous prostate tumors overexpressing PDGF D.
These novel findings support the utilization of cediranib, either alone or in combination with docetaxel, to treat bone metastatic prostate cancer exhibiting PDGF D expression.
PDGF D; Prostate Cancer; AZD2171; Metastasis; Markers
Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.
Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.
SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.
SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.
Ssanghwa-tang; Melanogenesis; p38 MAPK; PKA; MITF; Tyrosinase; B16F10 cells
Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.
Hepatitis C, Chronic; Ribavirin; Anemia; ITPA; IL28B
The aim of this study was to investigate the genetic association of the FAT gene with schizophrenia in the Korean population, as well as analyzing the association of FAT gene with clinical variables.
Four variants within the FAT gene were investigated in 189 patients with schizophrenia and 119 healthy controls (rs2306987 A/C, rs2306990 T/C, rs2637777 G/T, and rs2304865 G/C).
Significant association at the rs273777 with schizophrenia was observed; however, rs2306987, rs2306990, and rs2304865 were not associated with schizophrenia. Haplotype analyses revealed that the haplotype A/T/T/G was associated with a significantly protective effect. Sliding window analysis (rs2637777 G/T and rs2304865 G/C) revealed the more common T/G haplotype, included in the A/T/T/G protective combination, showed a small protective effect, in particular the effect was due to the rs273777 T variant (minor allele).
The present finding suggests that FAT polymorphism may play a putative role in the susceptibility to schizophrenia in the Korean population. Further studies using a larger number of subjects should be performed to determine whether the FAT gene polymorphism may be truly involved in the development of schizophrenia.
Association; Cadherins; Polymorphism; Schizophrenia; Korean
The etiology and pathophysiology of takotsubo cardiomyopathy have not yet been fully clarified. We report a case of takotsubo cardiomyopathy associated with severe hypocalcemia secondary to hypoparathyroidism. A 69-year-old woman presented with acute pulmonary edema caused by severe left ventricular dysfunction with apical ballooning compatible with takotsubo cardiomyopathy. Laboratory tests revealed severe hypocalcemia secondary to idiopathic hypoparathyroidism. Coronary angiography showed normal coronary artery function. Her symptoms and signs of heart failure improved dramatically with the correction of hypocalcemia through calcium and calcitriol replacement.
Takotsubo cardiomyopathy; Hypocalcemia; Hypoparathyroidism
To investigate the effect of CoenzymeQ10 (CoQ10) on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA).
Materials and Methods
OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration of CoQ10 was initiated on day 4 after MIA injection. Pain severity was assessed by measuring secondary tactile allodynia using the von Frey assessment test. The degree of cartilage degradation was determined by measuring cartilage thickness and the amount of proteoglycan. The mankin scoring system was also used. Expressions of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), IL-6, IL-15, inducible nitric oxide synthase (iNOS), nitrotyrosine and receptor for advanced glycation end products (RAGE) were analyzed using immunohistochemistry.
Treatment with CoQ10 demonstrated an antinociceptive effect in the OA animal model. The reduction in secondary tactile allodynia was shown by an increased pain withdrawal latency and pain withdrawal threshold. CoQ10 also attenuated cartilage degeneration in the osteoarthritic joints. MMP-13, IL-1β, IL-6, IL-15, iNOS, nitrotyrosine and RAGE expressions were upregulated in OA joints and significantly reduced with CoQ10 treatment.
CoQ10 exerts a therapeutic effect on OA via pain suppression and cartilage degeneration by inhibiting inflammatory mediators, which play a vital role in OA pathogenesis.
Filaggrin (FLG) is a key protein that facilitates the terminal differentiation of the epidermis and the formation of the skin barrier. Recent studies showed that atopic dermatitis (AD) associates closely with loss-of-function mutations in the FLG gene. Asian and European populations differ in the frequencies of FLG mutations. Several FLG mutations, including 3321delA, E2422X, K4671X, S2554X, and R501X, occur frequently in Chinese and Japanese populations. The association between three FLG null mutations and AD in Korean children was investigated.
The FLG mutations in 1,430 children (aged 0-18 years) with AD and 862 control subjects were genotyped by using the TaqMan assay.
The FLG null mutation E2422X was not detected in any patients with AD or control subjects. The R501X null mutation was detected in only one child with AD (0.1%). Children with AD had the 3321delA deletion significantly more frequently (2.4%) than the control subjects (0.0%, P<0.001). Children with AD also had a significantly higher combined allele frequency of the three FLG null mutations (2.6%) than the controls (0.0%, P<0.001). The 3321delA null mutation did not associate significantly with AD severity (P=0.842). When the patients with AD were divided into allergic AD and non-allergic AD patient groups, these two groups did not differ in terms of the frequency of 3321delA.
The Korean children had a lower frequency of FLG mutations than European populations. FLG null mutations may be associated with the development of AD in Korean children.
Filaggrin; atopic dermatitis; mutation; skin barrier
Recurrence after hepatic resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). We identified prognostic factors affecting overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatic resection.
This study was of a retrospective cohort design, and 126 patients who underwent hepatic resection for HCC at Gachon University Gil Medical Center between January 2005 and December 2010 were enrolled. Various clinical, laboratory, and pathological data were evaluated to determine the prognostic factors affecting OS and DFS.
Two- and 4-year OS and 2- and 4-year DFS were 78.1% and 65% and 51.1% and 26.6%, respectively. In a multivariate analysis, preoperative α-fetoprotein (> 400 ng/mL), tumor size (≥ 5 cm), multiple tumors (two or more nodules), presence of portal vein invasion, modified Union for International Cancer Control (UICC) stage III/IV, and Barcelona Clinic Liver Cancer (BCLC) stage B/C were independent prognostic factors affecting a shorter OS. In the multivariate analysis, presence of microvascular invasion, modified UICC stage III/IV, and BCLC stage B/C were independent prognostic factors for a shorter DFS.
The presence of vascular invasion was an independent poor prognostic factor for OS and DFS in patients with HCC after hepatic resection. Thus, close postoperative surveillance for early detection of recurrence and additional treatments are urgently needed in patients with vascular invasion after hepatic resection.
Carcinoma, hepatocellular; Hepatic resection; Prognosis; Vascular invasion
To suggest a new useful diagnostic technique, principles of the selective excitation technique-magnetic resonance images (Proset-MRI), and to know the precise radiologic findings that can prove symptomatic foraminal and extraforaminal stenosis at L5-S1.
Nineteen patients with symptomatic L5-S1 stenosis were checked by Proset-MRI. Four patients were performed decompressive surgery and 15 patients were performed selective nerve root block (SNRB) at L5. The pain scale of patients was checked by Visual Analogue Scale (VAS) scores at the pre- and post-treatment state.
Proset-MRI findings of patients with symptomatic stenosis are root swelling (RS) and indentation. The comparisons with VAS scores had a meaningful statistical result at each RS (p<0.01) and indentation (p<0.01). However, the findings of RS combined with indentation lacked statistical significance (p=0.0249). In addition, according to a comparison with the treatment modalities, reducing of VAS scores had statistical meaningful significance in decompressive surgery cases (p<0.01), and also in SNRB cases (p<0.01) after a 3-month follow-up period.
The three dimensional Proset-MRI is very useful and sensitive technique to diagnose the symptomatic foraminal and extraforaminal stenosis at L5-S1.
Proset-MRI; Foraminal and extraforaminal stenosis; Nerve root swelling; Indentation
The occurrence of numerous cases of interstitial lung disease in children (chILD) every spring in Korea starting in 2006 raised suspicion about a causal relationship with the use of humidifier disinfectants (HDs). The aim of this study was to evaluate the association between HD use and the risk of chILD.
This retrospective, 1∶3 matched case-control study consisted of 16 cases of chILD that had developed between 2010 and 2011. The three groups of parallel controls (patients with acute lobar pneumonia, asthma, and healthy children) were matched by age, gender, and index date. Indoor/outdoor environmental risk factors, including HD use, were investigated by asking the guardians to complete a questionnaire.
The median age of the affected children (43.8% male) was 26 months (18.25–36.25). The chILD group did not differ significantly from the control groups with respect to socio-demographic and clinical variables. Indoor and outdoor environmental factors were not associated with a risk of chILD. However, the previous use of HDs (OR; 2.73. 95% CI; 1.41–5.90, P = 0.00) were independently associated with an increased risk.
This study showed that HDs, which are widely used in South Korea in the winter season, independently increased the risk of chILD in spring. Therefore, continuous monitoring and, if needed, changes in policy are essential to prevent and control pediatric diseases caused by toxic chemicals.
Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (β-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein kinases (MAPKs: ERK, p38 MAPK and JNK) and Akt. Inhibition of ERK, p38 MAPK or JNK by specific inhibitors induced a dramatic reduction in Wnt5a-induced CCL2 production. Supernatant collected from lipopolysaccharide-stimulated macrophages induced neutrophil chemotaxis, which was significantly inhibited by anti-Wnt5a antibody. Our results suggested that Wnt5a may contribute to neutrophil recruitment, mediating the inflammation response.
chemotaxis; Gi-protein coupled receptor; neutrophils; Wnt5a
Patients with HPV-positive oropharyngeal cancer show better tumor response to radiation or chemotherapy than patients with HPV-negative cancer. HPV oncoprotein E6 binds and degrades a typically wild-type p53 protein product. However, HPV16 infection and p53 mutation infrequently coexist in a subset of HNSCCs. The purpose of this study was to investigate the mechanisms through which tumor biology and molecular genetic mechanisms change when two HPV-negative, p53-mutated oropharyngeal cell lines (YD8, non-disruptive p53 mutation; YD10B, disruptive p53 mutation) derived from patients with a history of heavy smoking are transfected with HPV E6 and E7 oncogenes in vitro. Transfection with HPV E6 and E7 oncogenes in YD8, reduced the abundance of proteins encoded by tumor suppressor genes, such as p-p53 and p-Rb. Cell proliferative activity was increased in the cells transfected with E6E7 compared to cells transfected with vector alone (P=0.09), whereas the invasiveness of E6E7-transfected cells was significantly reduced (P=0.02). cDNA microarray of the transfected cells with E6E7 showed significant changes in mRNA expression in several signaling pathways, including focal adhesion, JAK-STAT signaling pathway, cell cycle and p53 signaling pathway. Regarding the qPCR array for the p53 signaling pathway, the mRNA expression of STAT1 was remarkably upregulated by 6.47-fold (P<0.05); in contrast, IGF-1R was significantly downregulated by 2.40-fold in the YD8-vector compared toYD8-E6E7 (P<0.01). Finally, data collected from these two array experiments enabled us to select two genes, STAT1 and IGF-1R, for further study. In immunohistochemical study, nuclear STAT1 expression was slightly higher in HPV-positive compared to HPV-negative oropharyngeal tumors (P=0.18); however, cytoplasmic STAT1 was significantly lower in HPV-positive cases (P=0.03). IGF-1R expression levels were remarkably lower in HPV-positive compared to HPV-negative cases (P=0.01). Our data suggest that upregulated STAT1 and interferon signals by HPV16 E6 and E7 genes may play a major role in the relatively favorable prognosis for HPV-positive oropharyngeal squamous cell carcinoma cases with non-disruptive p53 mutations.
human papillomavirus; E6E7; head and neck squamous cell carcinoma; cDNA microarray; qRT-PCR array; JAK-STAT signal; STAT1; IGF-1R
The KRAS gain-of-function mutation confers intrinsic resistance to targeted anti-cancer drugs and cytotoxic chemotherapeutic agents, ultimately leading to treatment failure. KRAS mutation frequency in lung adenocarcinoma is ~15–30%. Novel therapeutic strategies should be developed to improve clinical outcomes in these cases. Deregulation of the p16/cyclin-dependent kinase (CDK) 4/retinoblastoma (Rb) pathway is frequently observed in various cancers and it represents an attractive therapeutic target. We compared the anti-tumor efficacy of genetically knocked-down CDK4 and a pharmacological inhibitor of CDK4/6, CINK4, in KRAS mutation-positive lung adenocarcinoma cells. We also investigated changes in anti-proliferative activity and downstream molecules with these treatments in combination with paclitaxel. CDK4 short interfering RNA (siRNA) significantly increased paclitaxel sensitivity in KRAS mutation-positive H23 cells. CINK4 demonstrated concentration- and time-dependent anti-proliferative activity in 5 adenocarcinoma lines. CINK4 induced G1 arrest by downregulating the p16/cyclin D1/Rb pathway, resulting in apoptotic induction via increased expression of cleaved caspase3, cleaved PARP and Bax. Combined CINK4 and paclitaxel produced synergistic anti-proliferative activity and increased apoptosis through reduced cyclin D1 and Bcl-2 in KRAS mutation-positive cancer cells. These data suggest CDK4 is a promising target for development of anti-cancer drugs and CINK4 combined with paclitaxel may be an effective therapeutic strategy for enhancing anti-tumor efficacy in KRAS mutation-positive lung adenocarcinoma.
NSCLC; KRAS; CDK4 siRNA; CDK4/6 inhibitor; paclitaxel; combination; synergistic
After maternal intake, nicotine crosses the placental barrier and causes severe embryonic disorders and fetal death. In this study, we investigated whether β-carotene has a beneficial effect against nicotine-induced teratogenesis in mouse embryos (embryonic day 8.5) cultured for 48 h in a whole embryo culture system. Embryos exposed to nicotine (1 mM) exhibited severe morphological anomalies and apoptotic cell death, as well as increased levels of TNF-α, IL-1β, and caspase 3 mRNAs, and lipid peroxidation. The levels of cytoplasmic superoxide dismutase (SOD), mitochondrial manganese-dependent SOD, cytosolic glutathione peroxidase (GPx), phospholipid hydroperoxide GPx, hypoxia inducible factor 1α, and Bcl-xL mRNAs decreased, and SOD activity was reduced compared to the control group. However, when β-carotene (1 × 10−7 or 5 × 10−7μM)
was present in cultures of embryos exposed to nicotine, these parameters improved significantly. These findings indicate that β-carotene effectively protects against nicotine-induced teratogenesis in mouse embryos through its antioxidative, antiapoptotic, and anti-inflammatory activities.
KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]-3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with 64Cu-DOTA-VEGF121. KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups. After injections occurred daily for 28 days, all groups of mice underwent post-treatment microPET imaging after injection with 64Cu-DOTA-VEGF121. The post-treatment images showed high tumor uptake in the control group and reduced tumor uptake in both the blocking and treatment groups. ROI analysis of the tumor images revealed 6.25%±1.18% ID/g at 1 h, 6.55%±0.69% ID/g at 2 h, and 4.68%±0.63% ID/g at 16 h in the control group; 3.87%±0.45% ID/g at 1 h, 4.50%±0.44% ID/g at 2 h, and 3.63%±0.25% ID/g at 16 h in the blocking group; and 4.03%±0.74% ID/g at 1 h, 4.37%±0.67% ID/g at 2 h, and 3.83%±0.90% ID/g at 16 h in the treatment group. Biodistribution obtained after the post-treatment microPET imaging also demonstrated high tumor uptake (3.74%±0.27% ID/g) in the control group and reduced uptakes in both the blocking group (2.69%±0.73% ID/g, P<.05) and the treatment group (3.11%±0.25% ID/g, P<.05), which correlated well with microPET imaging data. Immunofluorescence analysis showed higher levels of VEGFR2 and CD31 expressions in tumor tissues of the control and blocking groups than in tumor tissues of the treatment group. These results suggest that the antiangiogenic activity of KR-31831 is mediated through VEGFR2 and microPET serves as a useful molecular imaging tool for evaluation of a newly developed angiogenesis inhibitor, KR-31831.
KR-31831; 64Cu-DOTA-VEGF121; MicroPET; VEGFR2; Angiogenesis
Fusiform aneurysms on the basilar artery (BA) trunk are rare. The microsurgical management of these aneurysms is difficult because of their deep location, dense collection of vital cranial nerves, and perforating arteries to the brain stem. Endovascular treatment is relatively easier and safer compared with microsurgical treatment. Selective occlusion of the aneurysmal sac with preservation of the parent artery is the endovascular treatment of choice. But, some cases, particularly giant or fusiform aneurysms, are unsuitable for selective sac occlusion. Therefore, endovascular coiling of the aneurysm with parent vessel occlusion is an alternative treatment option. In this situation, it is important to determine whether a patient can tolerate parent vessel occlusion without developing neurological deficits. We report a rare case of fusiform aneurysms in the BA trunk. An 18-year-old female suffered a headache for 2 weeks. Computed tomography and magnetic resonance image revealed a fusiform aneurysm of the lower basilar artery trunk. Digital subtraction angiography revealed a 7.1×11.0 mm-sized fusiform aneurysm located between vertebrovasilar junction and the anterior inferior cerebellar arteries. We had good clinical result using endovascular coiling of unruptured fusiform aneurysm on the lower BA trunk with parent vessel occlusion after confirming the tolerance of the patient by balloon test occlusion with induced hypotension and accompanied by neurophysiologic monitoring, transcranial Doppler and single photon emission computed tomography. In this study, we discuss the importance of preoperative meticulous studies for avoidance of delayed neurological deficit in the patient with fusiform aneurysm on lower basilar trunk.
Cerebral aneurysm; Fusiform aneurysm; Balloon test occlusion; Provocative test; Embolization
A suite of eight cationic, tetra-metallic molecular rectangles (1–8) was generated via coordination-driven self-assembly using four dicarboxylate-bridged arene-Ru precursors (A1–A4) with one of two dipyridyl ligands (D1, D2). The high-yielding (84–92%) rectangles were characterized by 1H NMR and HR-ESI-MS to support their structural assignments. The molecular structure of 5 was determined by single crystal X-ray analysis, which indicated that two D2 ligands bridge two A1 acceptors to form a rectangular construct. The photophysical properties of these metalla-rectangles and their molecular precursors were also investigated, as well as an MTT assay to evaluate the in vitro cytotoxicities relative to two chemotherapeutic agents, cisplatin and doxorubicin. MTT assays were conducted using SK-hep-1 (liver cancer) and HCT-15 (colon cancer) human cancer cell lines. Compounds 3, 4, 7 and 8 showed significant activity, with IC50 values comparable to those of cisplatin and doxorubicin.
Oyaksungisan (OY) is a traditional herbal formula broadly used to treat beriberi, vomiting, diarrhea, and circulatory disturbance in Asian countries from ancient times. The effect of OY on cancer, however, was not reported until now. In this study, we have demonstrated that OY inhibits cell proliferation and induces cell death via modulating the autophagy on human colon cancer cells. In HCT116 cells, OY increased the ratio of LC3-II/LC3-I, a marker of autophagy, and treatment with 3-MA, an inhibitor of autophagy, and considerably reduced the formation of autophagosomes. In addition, OY regulated mitogen-activated protein kinase (MAPK) cascades; especially, JNK activation was closely related with autophagy effect by OY in HCT116 cells. Our results indicate that autophagy induction is responsible for the antiproliferative effect by OY, despite the weak apoptosis induction in HCT116 cells. In conclusion, OY might have a potential to be developed as an herbal anticancer remedy.
Genotype C is the principal type of hepatitis B virus (HBV) in Koreans and is associated with poor prognosis for peginterferon α-2a therapy. The efficacy of and compliance to peginterferon α-2a therapy were investigated in Koreans with hepatitis B in a real clinical setting.
Hepatitis B patients treated with peginterferon α-2a from 2008 to 2011 at four university hospitals were consecutively enrolled.
Eighty-eight patients were enrolled; 67 were hepatitis B e antigen (HBeAg)-positive. The mean treatment period was 36.1±15.2 weeks. In 26.1% of patients, treatment was discontinued due to insufficient antiviral effects and adverse events. At 24 weeks after treatment, 10/42 (23.8%) HBeAg-positive patients achieved both HBV DNA suppression to <2,000 IU/mL and HBeAg loss/seroconversion. For HBeAg-negative patients, 10/13 (76.9%) achieved HBV DNA suppression to <2,000 IU/mL at 24 weeks after treatment. During the follow-up period, 15 (30.6%) of the 49 patients who achieved HBV DNA suppression to 2,000 IU/mL developed a breakthrough HBV DNA level of >2×106 IU/mL.
Peginterferon α-2a therapy in Koreans with hepatitis B in a real clinical setting resulted in a lower virologic response, as compared to Western individuals, but a favorable durability. There is a need to reduce the high rate of premature discontinuation compared to the controlled studies.
Peginterferon; Chronic hepatitis B; Asian continental ancestry group
Hepatitis C; Peginterferon; Ribavirin; Korean
To determine whether a routine ultrasonography (US) is necessary for diagnosis of developmental dysplasia of hip (DDH), presenting with congenital muscular torticollis (CMT).
Cases of 133 patients (81 males, 52 females) diagnosed as CMT were reviewed, retrospectively. We reviewed the medical charts and diagnostic examination. We also assessed the coincidence of CMT and DDH, and investigated the clinical features of CMT related to DDH.
Twenty (15.0%) patients out of 133 CMT patients were diagnosed as having DDH by US. Of whom, 8 patients were radiographically positive and 4 patients were both clinically and radiographically positive. Nine patients were treated with a harness and 1 of them needed closed reduction and casting. Out of 9 patients treated with a harness, only 4 were clinically positive. The difference and ratio of the sternocleidomastoid (SCM) muscle thickness between the normal and abnormal side was significantly greater in DDH patients (p=0.014). Further, receiver operating characteristic analysis showed when the SCM ratio is greater than 2.08 and the SCM difference is greater than 6.1 mm, the efficiency of US for the diagnosis of the DDH was found to be the best (p<0.05).
To evaluate DDH, physical examination showed low sensitivity and radiologic study has limitation for the child before 4 to 6 months of age. Therefore, we recommend that hip is screened by US for the diagnosis of DDH associated with CMT when physical examination is positive or CMT patients with large SCM difference and high SCM ratio.
Torticollis; Hip dysplasia; Ultrasonography
In order to enhance the electron transport on the photoelectrodes of dye-sensitized solar cells, one-dimensional rutile nanorods were prepared using electrospun TiO2 nanofibers. The grain size of the nanorods increased with increasing temperature. Electrochemical impedance spectroscopy measurements revealed reduced interface resistance of the cells with the one-dimensional rutile nanorods due to the improved electron transport and the enhanced electrolyte penetration. Intensity-modulated photocurrent/photovoltage spectroscopy showed that the one-dimensional rutile nanorods provided the electrons with a moving pathway and suppressed the recombination of photogenerated electrons. However, an excessive quantity of rutile nanorods created an obstacle to the electrons moving in the TiO2 thin film. The photoelectrode with 7 wt.% rutile nanorods optimized the performance of the dye-sensitized solar cells.
One-dimensional TiO2 nanorods; Photoelectrode; Electron transfer; Dye-sensitized solar cells
The objective of this study was to evaluate a monoclonal antibody-based test to detect Helicobacter pylori-specific antigen in gastric aspirates from humans.
Sixty-one volunteers were enrolled in the study. All of the subjects underwent a 13C-urea breath test (UBT) before esophagogastroduodenoscopy. Gastric aspirates were analyzed for pH and ammonia and used for polymerase chain reaction (PCR), culture, and monoclonal antibody-based detection of H. pylori. Multiple biopsies of the gastric antrum and body were obtained for a rapid urease test (RUT) and histological evaluation.
Thirty-six subjects were H. pylori-positive and 25 were H. pylori-negative according to the UBT results. Compared with the H. pylori-negative subjects, H. pylori-positive subjects had a higher pH (4.77±1.77 vs 3.49±1.30, p<0.05) and ammonia level (1,130.9±767.4 vs 184.2±126.3, p<0.0001). The sensitivities and specificities of the PCR test, RUT, culture test, and monoclonal antibody-based test were 100% and 72%, 89% and 100%, 47% and 100%, and 78% and 100%, respectively.
The monoclonal antibody-based test for diagnosing H. pylori infection in gastric aspirates has increased sensitivity compared with the culture test and specificity as high as that of the RUT. The test may be useful as an additive test for examining gastric aspirates.
Helicobacter pylori; Gastric aspirate; Monoclonal antibody-based test