Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients:Dabigatran versus rivaroxaban

Abstract Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality

Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 10⁶autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.</p> <p>Results</p> <p>Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)</p> <p>Conclusion</p> <p>ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.</p

Organic Electrochemical Transistors/SERS-Active Hybrid Biosensors Featuring Gold Nanoparticles Immobilized on Thiol-Functionalized PEDOT Films

In this study we immobilized gold nanoparticles (AuNPs) onto thiol-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) films as bioelectronic interfaces (BEIs) to be integrated into organic electrochemical transistors (OECTs) for effective detection of dopamine (DA) and also as surface-enhanced Raman scattering (SERS)—active substrates for the selective detection of p-cresol (PC) in the presence of multiple interferers. This novel PEDOT-based BEI device platform combined (i) an underlying layer of polystyrenesulfonate-doped PEDOT (PEDOT:PSS), which greatly enhanced the transconductance and sensitivity of OECTs for electrochemical sensing of DA in the presence of other ascorbic acid and uric acid metabolites, as well as amperometric response toward DA with a detection limit (S/N = 3) of 37 nM in the linear range from 50 nM to 100 μM; with (ii) a top interfacial layer of AuNP-immobilized three-dimensional (3D) thiol-functionalized PEDOT, which not only improved the performance of OECTs for detecting DA, due to the signal amplification effect of the AuNPs with high catalytic activity, but also enabled downstream analysis (SERS detection) of PC on the same chip. We demonstrate that PEDOT-based 3D OECT devices decorated with a high-density of AuNPs can display new versatility for the design of next-generation biosensors for point-of-care diagnostics

HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma

Carcinogenesis is determined based on both cell proliferation and death rates. Recent studies demonstrate that heat shock proteins (HSPs) regulate apoptosis. HLJ1, a member of the DnaJ-like Hsp40 family, is a newly identified tumor suppressor protein closely related to relapse and survival in non-small cell lung cancer (NSCLC) patients. However, its role in apoptosis is currently unknown. In this study, NSCLC cell lines displaying varying HLJ1 expression levels were subjected to ultraviolet (UV) irradiation, followed by flow cytometry. Interestingly, the percentages of apoptotic cells in the seven cell lines examined were positively correlated with HLJ1 expression. Enforcing expression of HLJ1 in low-HLJ1 expressing highly invasive cells promoted UV-induced apoptosis through enhancing JNK and caspase-3 activation in NSCLC. Additionally, UV irradiation led to reduced levels of HLJ1 predominantly in apoptotic cells. The pan-caspase inhibitor, zVAD-fmk and caspase-3-specific inhibitor, DEVD-fmk, prevented UV-induced degradation of HLJ1 by the late stage of apoptosis. Further experiments revealed a non-typical caspase-3 cleavage site (MEID) at amino acid 125–128 of HLJ1. Our results collectively suggest that HLJ1 is a novel substrate of caspase-3 during the UV-induced apoptotic process

Targeted Overexpression of Osteoactivin in Cells of Osteoclastic Lineage Promotes Osteoclastic Resorption and Bone Loss in Mice

This study sought to test whether targeted overexpression of osteoactivin (OA) in cells of osteoclastic lineage, using the tartrate-resistant acid phosphase (TRAP) exon 1B/C promoter to drive OA expression, would increase bone resorption and bone loss in vivo. OA transgenic osteoclasts showed ∼2-fold increases in OA mRNA and proteins compared wild-type (WT) osteoclasts. However, the OA expression in transgenic osteoblasts was not different. At 4, 8, and 15.3 week-old, transgenic mice showed significant bone loss determined by pQCT and confirmed by μ-CT. In vitro, transgenic osteoclasts were twice as large, had twice as much TRAP activity, resorbed twice as much bone matrix, and expressed twice as much osteoclastic genes (MMP9, calciton receptor, and ADAM12), as WT osteoclasts. The siRNA-mediated suppression of OA expression in RAW264.7-derived osteoclasts reduced cell size and osteoclastic gene expression. Bone histomorphometry revealed that transgenic mice had more osteoclasts and osteoclast surface. Plasma c-telopeptide (a resorption biomarker) measurements confirmed an increase in bone resorption in transgenic mice in vivo. In contrast, histomorphometric bone formation parameters and plasma levels of bone formation biomarkers (osteocalcin and pro-collagen type I N-terminal peptide) were not different between transgenic mice and WT littermates, indicating the lack of bone formation effects. In conclusion, this study provides compelling in vivo evidence that osteoclast-derived OA is a novel stimulator of osteoclast activity and bone resorption

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Genome-Wide Association Study of Treatment Refractory Schizophrenia in Han Chinese

We report the first genome-wide association study of a joint analysis using 795 Han Chinese individuals with treatment-refractory schizophrenia (TRS) and 806 controls. Three loci showed suggestive significant association with TRS were identified. These loci include: rs10218843 (P = 3.04×10−7) and rs11265461 (P = 1.94×10−7) are adjacent to signaling lymphocytic activation molecule family member 1 (SLAMF1); rs4699030 (P = 1.94×10−6) and rs230529 (P = 1.74×10−7) are located in the gene nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1); and rs13049286 (P = 3.05×10−5) and rs3827219 (P = 1.66×10−5) fall in receptor-interacting serine/threonine-protein kinase 4 (RIPK4). One isolated single nucleotide polymorphism (SNP), rs739617 (P = 3.87×10−5) was also identified to be associated with TRS. The -94delATTG allele (rs28362691) located in the promoter region of NFKB1 was identified by resequencing and was found to associate with TRS (P = 4.85×10−6). The promoter assay demonstrated that the -94delATTG allele had a significant lower promoter activity than the -94insATTG allele in the SH-SY5Y cells. This study suggests that rs28362691 in NFKB1 might be involved in the development of TRS