Although the significant risk factors for hepatocellular carcinoma (HCC) are well known from epidemiological studies, diagnosis of this disease at an early stage is difficult, and HCC remains one of ...the leading causes of cancer death worldwide. Thus, to identify any useful HCC‐related biomarkers is still a need. We performed SELDI‐TOF MS to identify differentially expressed proteins in HCC serum using weak cation exchange protein chips. Protein characterization was performed by 2‐DE separation and nano flow LC‐MS/MS. A total of 55 sera were collected from HCC patients and compared with those from 48 patients with chronic hepatitis and 9 healthy individuals. A candidate marker of about 8900 Da was detected as differentially expressed in patients with chronic hepatitis C and hepatitis C virus (HCV)‐related HCC. We identified this differentially expressed protein as complement C3a. The expression of C3a in HCC sera was further validated by PS20 chip immunoassay and Western blotting. Complement C3a was found to be elevated in patients with chronic hepatitis C and HCV‐related HCC. The combination of SELDI‐TOF MS and 2‐DE provides a solution to identify disease‐associated serum biomarkers.
Background
“Precision medicine” is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The ...treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women.
Methods
GEO Datasets for non-Asian (12 groups,
n
= 1450) and Taiwanese (3 groups,
n
= 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed. Then, using TNBC cell lines of different subtypes, namely, MDA-MB-468 (basal-like1, BL1), MDA-MB-231 (mesenchymal stem like, MSL), BT-549 (mesenchymal, M), MDA-MB-453 (luminal androgen receptor, LAR), and DU4475 (immunomodulatory, IM), real-time PCR in triplicate for 47 genes signatures were performed to validate the specificity of these subtypes.
Results
The results showed that the percentage of TNBC subtypes in non-Asian women, namely, BL1, BL2, IM, M, MSL, and LAR was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively. When data from Taiwanese were normalized and clustered, five TNBC subtypes, namely, BL (8.94%), IM (13.82%), M (22.76%), MSL (30.89%), and LAR (23.58%), were classified. Real-time PCR validated the specificity of these subtypes. Besides, the presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification.
Conclusion
Our data suggested that there exist different presentations between non-Asian and Taiwanese TNBC subtypes, which provides important information when selection of therapeutic targets or designs for clinical trials for TNBC patients.
To report the objective outcome, subjective measurement of incontinence-related quality of life (QoL) for female urodynamic stress incontinence (USI) after transobturator sling surgery (TVT-O) and to ...evaluate the effects of surgical failure and complications on QoL.
We analyzed the data from women who underwent TVT-O for USI and completed two validated QoL questionnaires, the Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) preoperatively and at least 12 months postoperatively. We evaluated the subjective results of QoL questionnaires, objective results and compare the effect of QoL on those with surgical failure and complications after TVT-O surgery.
A total of 78 women were followed for a median of 13.5 months (range 12–15 months) after surgery. Within this group, 75 (96%) were considered subjectively cured or improved after TVT-O. There were significant improvements in the IIQ-7 and total UDI-6 scores postoperatively, as well as in the UDI-6 subscales for urge, stress and voiding dysfunction symptoms. Even the 18 women with objective urodynamic failure had significant improvement in QoL scores. For those with surgical related complications, the QoL scores were also significantly improved.
TVT-O for USI resulted in improvement of incontinence-related QoL including urgency, stress, and voiding dysfunction symptoms. Surgical failure and complications didn't impair postoperative QoL.
Persistent exacerbation of a peptic ulcer may lead to a complicated peptic ulcer (perforation or/and bleeding). The management of complicated peptic ulcers has shifted from acid-reducing vagotomy, ...drainage, and gastrectomy to simple local suture or non-operative (endoscopic/angiographic) hemostasis. We were interested in the long-term effects of this trend change. In this study, complicated peptic ulcer patients who received acid-reducing vagotomy were compared with those who received simple suture/hemostasis to determine the risk of ischemic heart disease (IHD).This retrospective cohort study analyzed 335,680 peptic ulcer patients recorded from 2000 to 2006 versus 335,680 age-, sex-, comorbidity-, and index-year matched comparisons. Patients with Helicobacter pylori (HP) infection were excluded. In order to identify the effect of vagus nerve severance, patients who received gastrectomy or antrectomy were also excluded. The incidence of IHD in both cohorts, and in the complicated peptic ulcer patients who received acid-reducing vagotomy versus those who received simple suture or hemostasis was evaluated.The overall incidence of IHD was higher in patients with peptic ulcer than those without peptic ulcer (17.00 vs 12.06 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.46 based on multivariable Cox proportional hazards regression analysis controlling for age, sex, Charlson's comorbidity index, and death (competing risk). While comparing peptic ulcer patients with acid-reducing vagotomy to those with simple suture/hemostasis or those without surgical treatment, the aHR (0.58) was the lowest in the acid-reducing vagotomy group.Patients with peptic ulcer have an elevated risk of IHD. However, complicated peptic ulcer patients who received acid-reducing vagotomy were associated with reduced risk of developing IHD.
Apical constriction, or a reduction in size of the apical domain, underlies many morphogenetic events during development. Actomyosin complexes play an essential role in apical constriction; however, ...the detailed analysis of molecular mechanisms is still pending. Here, we show that Lim domain only protein 7 (Lmo7), a multidomain adaptor at apical junctions, promotes apical constriction in the Xenopus superficial ectoderm, whereas apical domain size increases in Lmo7-depleted cells. Lmo7 is primarily localized at apical junctions and promotes the formation of the dense circumferential actomyosin belt. Strikingly, Lmo7 binds non-muscle myosin II (NMII) and recruits it to apical junctions and the apical cortex. This NMII recruitment is essential for Lmo7-mediated apical constriction. Lmo7 knockdown decreases NMIIA localization at apical junctions and delays neural tube closure in Xenopus embryos. Our findings suggest that Lmo7 serves as a scaffold that regulates actomyosin contractility and apical domain size.
The development of novel macromolecular contrast agents that offer enhanced relaxivity profiles at high magnetic fields have the potential to greatly improve the diagnosis, understanding, and ...treatment of disease. To this end, we have designed a monodiperse paramagnetic beta-cyclodextrin click cluster decorated with seven paramagnetic arms. A novel alkyne-functionalized diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and coupled to a per-azido-beta-cyclodextrin core (7) to yield the precursor macromolecule (8). After removal of the protecting groups and titrating with Gd (3+), the final paramagnetic click cluster, Gd10, was obtained. Luminescence measurements were carried out in H 2O and D 2O on an analogous structure, Eu10, and indicated that at each lanthanide has an average of 1.8 water exchange sites, which is important for enhancing relaxivity and MRI resolution. This discrete paramagnetic click cluster yields a high relaxivity profile (43.4 mM (-1) s (-1) per molecule and 6.2 mM (-1) s (-1) per Gd (3+) at 9.4 T) and enhanced contrast on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM (-1) s (-1) at 9.4 T). Moreover, the useful inclusion properties exhibited by beta-cyclodextrin also make this an excellent host scaffold to functionalize via noncovalent assembly with receptor specific targeting moieties for biomolecular imaging.
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is highly expressed in embryonic stem cells (ESCs) and its role in maintenance of pluripotency has been suggested ...previously. In epithelial cancer cells, activation of the EpCAM surface-to-nucleus signaling transduction pathway involves a number of membrane proteins. However, their role in somatic cell reprogramming is still unknown. Here we demonstrate that EpCAM and its associated protein, Cldn7, play a critical role in reprogramming. Quantitative RT-PCR analysis of Oct4, Sox2, Klf4, and c-Myc (OSKM) infected mouse embryonic fibroblasts (MEFs) indicated that EpCAM and Cldn7 were up-regulated during reprogramming. Analysis of numbers of alkaline phosphatase- and Nanog-positive clones, and the expression level of pluripotency-related genes demonstrated that inhibition of either EpCAM or Cldn7 expression resulted in impairment in reprogramming efficiency, whereas overexpression of EpCAM, EpCAM plus Cldn7, or EpCAM intercellular domain (EpICD) significantly enhanced reprogramming efficiency in MEFs. Furthermore, overexpression of EpCAM or EpICD significantly repressed the expression of p53 and p21 in the reprogramming MEFs, and both EpCAM and EpICD activated the promoter activity of Oct4. These observations suggest that EpCAM signaling may enhance reprogramming through up-regulation of Oct4 and possible suppression of the p53-p21 pathway. In vitro and in vivo characterization indicated that the EpCAM-reprogrammed iPSCs exhibited similar molecular and functional features to the mouse ESCs. In summary, our studies provide additional insight into the molecular mechanisms of reprogramming and suggest a more effective means of induced pluripotent stem cell generation.
EpCAM is highly expressed in ESCs. However, the role of EpCAM complex proteins in pluripotency reprogramming is still unknown.
Overexpression of EpCAM complex proteins significantly repressed the expression of p53 and enhanced reprogramming efficiency in MEFs.
EpCAM signaling enhance reprogramming through suppression of the p53-p21 pathway.
EpCAM signaling enhance reprogramming through suppression of the p53-p21 pathway.
Intravesical hyaluronic acid (HA) therapy is one of acceptable methods to treat bladder pain and storage symptoms (i.e., urgency, frequency and nocturia) of interstitial cystitis/bladder pain ...syndrome (IC/BPS). We aim to assess the impacts of intravesical HA on bladder pain and storage symptoms, respectively, and to investigate their associated factors in patients with IC/BPS.
In this prospective, multicenter study, 103 women with refractory IC/BPS undergoing a standard protocol of intravesical HA therapy were enrolled. A pain Visual Analog Scale (VAS) and the Interstitial Cystitis Symptom and Problem Index (ICSI & ICPI) were used to assess symptoms and bother associated with IC/BPS. The Scaled Global Response Assessment (GRA) was used to evaluate patients' perception of overall changes in bladder pain and storage symptoms, respectively, after treatment.
Mean age of participants was 43.6 ± 11.8 years. The average duration of symptoms was 5.1 ± 5.0 years. Significant improvements in pain VAS, ICSI and ICPI scores were observed after treatment. However, patients reported significantly different rates of moderate/marked improvement in bladder pain and storage symptoms (73.8% vs. 47.6%; P < 0.001) on the GRA, respectively. “Lower pain VAS score” and “reduced functional bladder capacity” were found to be the factors that adversely affected the treatment responses of bladder pain and storage symptoms, respectively, after repeated statistical analyses.
Bladder instillation of HA seemed more efficient in improving bladder pain than storage symptoms associated with IC/BPS. The persistence of bladder storage symptoms after treatment might result from a reduced functional bladder capacity.
Electroconvulsive therapy (ECT) is an effective treatment for schizophrenia, bipolar disorder, and major depressive disorder, and a temporary memory loss may occur after ECT. However, the association ...between ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, and the risk of dementia is yet to be examined.
This study aimed to clarify as to whether ECT is associated with the risk of dementia after ECT in patients with schizophrenia, bipolar disorder, and major depressive disorder, using Taiwan's National Health Insurance Research Database (NHIRD).
A total of 3,796 enrolled participants (schizophrenia, 46.68%; bipolar disorder, 11.77%; and major depressive disorder, 41.55%) with 994 patients who had received ECT and 2,982 controls matched for sex and age, between January 1, and December 31, 2000, were selected from the NHIRD. After adjusting for confounding factors, Fine and Gray's survival analysis was used to compare the risk of developing dementia during the 10 years of follow-up.
Of the study patients, 45 (4.53%) of them developed dementia when compared to 149 (5.0%) in the control group. Fine and Gray's survival analysis revealed that the study patients were not associated with an increased risk of dementia hazard ratio (HR) = 0.612, 95% confidence interval (CI) = 0.438-1.854,
= 0.325. After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 0.633 (95%
= 0.448 - 1.895,
= 0.304).
This study supports that ECT was not associated with the increased risk of dementia in patients with schizophrenia, bipolar disorder, and major depressive disorder, using the NHIRD.
Introduction:
Genetic susceptibility and immune dysregulation play important roles in the pathogenesis of Kawasaki disease (KD). However, it is still unclear whether KD causes immune disorder later ...in life or whether inherited susceptibility to immune disorders causes KD. The aim of this study was to elucidate whether inherited immune disease properties from mothers increase the risk of KD from a population-based perspective.
Method:
Taiwan's National Health Insurance Research Database was the main data source in this study. Parents and children were linked using the Taiwan Maternal and Child Health Database. Patients diagnosed with KD and younger than 18 years from 2004 to 2015 were enrolled as the study population. The control group was randomly selected from individuals without the diagnosis of KD matched by age, index year, sex, and urbanization level at a ratio of 1 to 10. The prevalence of maternal autoimmune and allergic diseases was compared between groups.
Results:
In total, 7,178 children were found to have been diagnosed with Kawasaki disease. Then 71,780 children matched by index year, gender, and urbanization were randomly selected to serve as the control group. Children born from mothers with asthma and allergic rhinitis had a higher risk of developing KD. Children of mothers with an autoimmune disorder had a significantly increased tendency to develop KD. Maternal numbers of autoimmune disorders showed a dose-dependent relationship with KD incidence.
Conclusion:
This is the first population-based study to investigate maternal immune diseases and the risk of KD in their children. Children of mothers with immune disorders tend to have a higher risk of KD.
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