IL-10 Inhibits Transforming Growth Factor-ß-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts

Transforming growth factor-ß (TGF-ß) is a key factor for understanding the pathogenesis of fibrotic disorders such as idiopathic pulmonary fibrosis (IPF). We have demonstrated that interleukin-10 (IL-10) suppresses TGF-ß-induced expression of type I collagen (COL1) mRNA in a human lung fibroblast cell line (WI-38). However, the inhibitory mechanism has not yet been clearly elucidated. Thus, in the current study, we investigate the effects of IL-10 blockade of TGF-ß signaling which regulates COL1 mRNA expression. In WI-38 cells, IL-10 inhibits TGF-ß-mediated phosphorylation of both, c-Jun HN2-terminal kinase (JNK) and p38, but does not suppress TGF-ß- mediated phosphorylation of Smad2 or affect TGF-ß-upregulation of Smad7 mRNA expression. In addition, SP600125 and SB203580, specific inhibitors of JNK and p38, respectively, attenuate TGF-ß-induced COL1 mRNA expression in WI-38 cells. These results suggest that IL-10 inhibits TGF-ß-induced COL1 mRNA expression via both JNK and p38 pathways but not Smad pathways in WI-38 cells. This inhibitory mechanism may provide a novel insight into therapeutic strategies for fibrotic disorders such as IPF

Novel method for immunofluorescence staining of mammalian eggs using non-contact alternating-current electric-field mixing of microdroplets

Recently, a new technique was developed for non-catalytically mixing microdroplets. In this method, an alternating-current (AC) electric field is used to promote the antigen-antibody reaction within the microdroplet. Previously, this technique has only been applied to histological examinations of flat structures, such as surgical specimens. In this study, we applied this technique for the first time to immunofluorescence staining of three-dimensional structures, specifically, mammalian eggs. We diluted an antibody against microtubules from 1:1,000 to 1:16,000, and compared the chromatic degree and extent of fading across dilutions. In addition, we varied the frequency of AC electricfield mixing from 5 Hz to 46 Hz and evaluated the effect on microtubule staining. Microtubules were more strongly stained after AC electric-field mixing for only 5 minutes, even when the concentration of primary antibody was 10 times lower than in conventional methods. AC electric-field mixing also alleviated microtubule fading. At all frequencies tested, AC electric-field mixing resulted in stronger microtubule staining than in controls. There was no clear difference in a microtubule staining between frequencies. These results suggest that the novel method could reduce antibody consumption and shorten immunofluorescence staining time

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A case of placental site trophoblastic tumor complicating nephrotic syndrome in which hysteroscopic biopsy did not yield a definitive diagnosis

Placental site trophoblastic tumor (PSTT) is the rarest subtype of gestational trophoblastic neoplasm. We present a case of PSTT complicating nephrotic syndrome. A 32-year-old woman experienced irregular menstrual bleeding and lower extremity edema 18 months after delivery. She was diagnosed with nephrotic syndrome and exaggerated placental site based on the hysteroscopic biopsy results. During follow-up, transvaginal color Doppler ultrasound showed an enlarged uterus filled with a hypervascular mass. Positron emission tomography–computed tomography showed diffuse accumulation in the entire uterus. The patient was diagnosed with PSTT only after total hysterectomy. Postoperatively, serum β-human chorionic gonadotropin decreased to within the normal range and her nephrotic syndrome resolved. She has remained without evidence of recurrence for 15 months. It is difficult to diagnose PSTT definitively. Most patients with PSTT are of reproductive age, therefore, to maintain fecundity, therapy development is expected

Negative effects of ocean acidification on two crustose coralline species using genetically homogeneous samples

We evaluated acidification effects on two crustose coralline algal species common to Pacific coral reefs, Lithophyllum kotschyanum and Hydrolithon samoense. We used genetically homogeneous samples of both species to eliminate misidentification of species. The growth rates and percent calcification of the walls of the epithallial cells (thallus surface cells) of both species decreased with increasing pCO2. However, elevated pCO2 more strongly inhibited the growth of L. kotschyanum versus H. samoense. The trend of decreasing percent calcification of the cell wall did not differ between these species, although intercellular calcification of the epithallial cells in L. kotschyanum was apparently reduced at elevated pCO2, a result that might indicate that there are differences in the solubility or density of the calcite skeletons of these two species. These results can provide knowledge fundamental to future studies of the physiological and genetic mechanisms that underlie the response of crustose coralline algae to environmental stresses

Structure–Property Relationship of Supramolecular Rotators of Coronene in Charge-Transfer Solids

Single crystals of charge-transfer (CT) complexes composed of the polyaromatic hydrocarbon, coronene, as an electron donor (D) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) analogues as electron acceptor (A) were obtained. Elucidation of crystal structures of CT complexes enables a systematic investigation of dynamic properties of coronene molecules lying in different types of crystalline environments. Solid-state ²H NMR spectra of CT complexes formed with deuterated coronene confirmed the in-plane 6-fold flipping motion of the coronene molecules. The dihedral angle between adjacent coronene and TCNQ analogue within the DA-type alternating π-column is closely correlated with the dynamic properties, such as rotational rate and activation energy. Side-by-side intermolecular hydrogen-bonding also seems to have an effect in ways that lead to the suppressed rotation. These findings would provide an initial step toward the selection, design, and engineering of counter components of supramolecular rotators in the CT solids

Structure–Property Relationship of Supramolecular Rotators of Coronene in Charge-Transfer Solids

Single crystals of charge-transfer (CT) complexes composed of the polyaromatic hydrocarbon, coronene, as an electron donor (D) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) analogues as electron acceptor (A) were obtained. Elucidation of crystal structures of CT complexes enables a systematic investigation of dynamic properties of coronene molecules lying in different types of crystalline environments. Solid-state ²H NMR spectra of CT complexes formed with deuterated coronene confirmed the in-plane 6-fold flipping motion of the coronene molecules. The dihedral angle between adjacent coronene and TCNQ analogue within the DA-type alternating π-column is closely correlated with the dynamic properties, such as rotational rate and activation energy. Side-by-side intermolecular hydrogen-bonding also seems to have an effect in ways that lead to the suppressed rotation. These findings would provide an initial step toward the selection, design, and engineering of counter components of supramolecular rotators in the CT solids

Structure–Property Relationship of Supramolecular Rotators of Coronene in Charge-Transfer Solids

Single crystals of charge-transfer (CT) complexes composed of the polyaromatic hydrocarbon, coronene, as an electron donor (D) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) analogues as electron acceptor (A) were obtained. Elucidation of crystal structures of CT complexes enables a systematic investigation of dynamic properties of coronene molecules lying in different types of crystalline environments. Solid-state ²H NMR spectra of CT complexes formed with deuterated coronene confirmed the in-plane 6-fold flipping motion of the coronene molecules. The dihedral angle between adjacent coronene and TCNQ analogue within the DA-type alternating π-column is closely correlated with the dynamic properties, such as rotational rate and activation energy. Side-by-side intermolecular hydrogen-bonding also seems to have an effect in ways that lead to the suppressed rotation. These findings would provide an initial step toward the selection, design, and engineering of counter components of supramolecular rotators in the CT solids