Characterization of endocrine disruption potentials of coastal sediments of Taean, Korea employing H295R and MVLN assays-Reconnaissance at 5years after Hebei Spirit oil spill.

Endocrine disrupting potentials were assessed for sediment samples collected near Hebei Spirit oil spill (HSOS) site, between December 2007 and January 2012. For comparison, major crude oil (CO) of HSOS, or its weathered form were assessed. Both raw extracts (REs) and their fractionated samples were tested using H295R and MVLNluc bioassays.

Systematic analysis of protein turnover in primary cells.

A better understanding of proteostasis in health and disease requires robust methods to determine protein half-lives. Here we improve the precision and accuracy of peptide ion intensity-based quantification, enabling more accurate protein turnover determination in non-dividing cells by dynamic SILAC-based proteomics. This approach allows exact determination of protein half-lives ranging from 10 to >1000 h.

Targeting Cyclin D-CDK4/6 Sensitizes Immune-Refractory Cancer by Blocking the SCP3-NANOG Axis.

Immunoediting caused by antitumor immunity drives tumor cells to acquire refractory phenotypes. We demonstrated previously that tumor antigen-specific T cells edit these cells such that they become resistant to CTL killing and enrich NANOG cancer stem cell-like cells. In this study, we show that synaptonemal complex protein 3 (SCP3), a member of the Cor1 family, is overexpressed in immunoedited cells and upregulates NANOG by hyperactivating the cyclin D1-CDK4/6 axis.

In silico profiling of systemic effects of drugs to predict unexpected interactions.

Identifying unexpected drug interactions is an essential step in drug development. Most studies focus on predicting whether a drug pair interacts or is effective on a certain disease without considering the mechanism of action (MoA). Here, we introduce a novel method to infer effects and interactions of drug pairs with MoA based on the profiling of systemic effects of drugs.

Stage-specific metabolic features of differentiating neurons: Implications for toxicant sensitivity.

Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors.

IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma.

Programmed death-ligand 1 (PD-L1) acts as an immune checkpoint inhibitor in various cancers. PD-L1 is known to be more frequently expressed in EBV (+) gastric cancer (GC). However, the mechanisms underlying the regulation of PD-L1 expression in EBV (+) GC remain unclear.

Alterations in gene expression in vitamin D-deficiency: Down-regulation of liver Cyp7a1 and renal Oat3 in mice.

The vitamin D-deficient model, established in the C57BL/6 mouse after 8 weeks of feeding vitamin D-deficient diets in the absence or presence of added calcium, was found associated with elevated levels of plasma parathyroid hormone (PTH) and plasma and liver cholesterol, and a reduction in cholesterol 7α-hydroxylase (Cyp7a1, rate-limiting enzyme for cholesterol metabolism) and renal Oat3 mRNA/protein expression levels. However, there was no change in plasma calcium and phosphate levels. Appraisal of the liver revealed an up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency.

Inhibiting Nuclear Phospho-Progesterone Receptor Enhances Antitumor Activity of Onapristone in Uterine Cancer.

Although progesterone receptor (PR)-targeted therapies are modestly active in patients with uterine cancer, their underlying molecular mechanisms are not well understood. The clinical use of such therapies is limited because of the lack of biomarkers that predict response to PR agonists (progestins) or PR antagonists (onapristone). Thus, understanding the underlying molecular mechanisms of action will provide an advance in developing novel combination therapies for cancer patients.

HPLC-MS/MS analysis of mesupron and its application to a pharmacokinetic study in rats.

Mesupron, the first-in-class inhibitor of urokinase-type plasminogen activator (uPA) is known to regulate cell proliferation and migration, and is under investigation for the treatment of metastatic breast cancer. In this study, a quantification method was developed for the determination of mesupron in rat plasma using liquid chromatography with a tandem mass spectrometry (LC-MS/MS). After protein precipitation with acetonitrile including itraconazole (internal standard, IS), the analytes were chromatographed on a reversed phased column with a mobile phase of acetonitrile and water (7:3, v/v, including 0.

Miniaturized, Battery-Free Optofluidic Systems with Potential for Wireless Pharmacology and Optogenetics.

Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools available to perform these experiments, such as optical fibers and metal cannula, are limited due to their tethered operation and lack of biomechanical compatibility. To address these issues, a miniaturized, battery-free, soft optofluidic system that can provide wireless drug delivery and optical stimulation for spatiotemporal control of the targeted neural circuit in freely behaving animals is reported.

Differential Effects of EGFL6 on Tumor versus Wound Angiogenesis.

Angiogenesis inhibitors are important for cancer therapy, but clinically approved anti-angiogenic agents have shown only modest efficacy and can compromise wound healing. This necessitates the development of novel anti-angiogenesis therapies. Here, we show significantly increased EGFL6 expression in tumor versus wound or normal endothelial cells.

CTCF-Mediated Chromatin Loops between Promoter and Gene Body Regulate Alternative Splicing across Individuals.

The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA.

Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs.

The intestinal mucosa and liver have long been considered as the main sites of drug metabolism, and the contribution of gut microbiota to drug metabolism has been under-estimated. However, it is now generally accepted that the gut microbiota plays an important role in drug metabolism prior to drug absorption or during enterohepatic circulation via various microbial enzymatic reactions in the intestine. Moreover, some drugs are metabolized by gut microbiota to specific metabolite(s) that cannot be formed in the liver.

Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain.

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) suffer from chronic pain that severely affects quality of life. Although the underlying pathophysiology is not well understood, inhibition of bladder sensory afferents temporarily relieves pain. Here, we explored the possibility that optogenetic inhibition of nociceptive sensory afferents could be used to modulate bladder pain.

A 10-Year Cone Beam Computerized Tomography Observation of the Buccal Bony Wall of an Immediately Placed Implant at the Anterior Maxilla: A Case Report.

Since the introduction of immediate implant placements, the buccal bony wall has been a major consideration for success due to its correlation with soft tissue contour and color. This report presents the stability of the buccal wall thickness of an immediately placed implant at the anterior maxilla over 10 years. Although the width of the buccal wall decreased at the 2-year post-op follow-up, it remained stable afterward according to cone beam computerized tomography (CBCT) scans.

Functional and Radiographic Outcomes After Arthroscopic Transosseous Suture Repair of Medium Sized Rotator Cuff Tears.

Purpose: To evaluate the functional and anatomical outcomes after arthroscopic transosseous suture (TOS) repair of 2 to 4 cm sized rotator cuff tears and to identify preoperative factors influencing repair failure.

Methods: From May 2013 to August 2014, patients with symptomatic 2 to 4 cm full-thickness tears underwent arthroscopic TOS repair, and those who could be followed up for a minimum of 2 years were included in this retrospective study. Functional and anatomical outcomes were analyzed up to 2 years postoperatively.

Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP).

Anti-vascular endothelial growth factor (VEGF) therapy has demonstrated efficacy in treating human metastatic cancers, but therapeutic resistance is a practical limitation and most tumors eventually become unresponsive. To identify microenvironmental factors underlying the resistance of cancer to antiangiogenesis therapy, we conducted genomic analyses of intraperitoneal ovarian tumors in which adaptive resistance to anti-VEGF therapy (B20 antibody) developed. We found that expression of the microseminoprotein, prostate-associated (MSMP) gene was substantially upregulated in resistant compared with control tumors.

Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes.

We report the unique role of CX3CL1 (or fractalkine) on CD11b myelomonocytic cells expressing CX3CR1, the only known receptor for CX3CL1, in promoting blood perfusion recovery. In a mouse ischemic hind-limb model, CD11b CX3CR1 cells migrated to ischemic femoral muscles through CX3CL1-mediated chemotaxis. CD11b CX3CR1 macrophages isolated from ischemic tissues [tissue (T)-CD11b CX3CR1 ] of muscle exert a proangiogenic effect through platelet factor-4 (CXCL4; PF-4) production.

miR-122-SOCS1-JAK2 axis regulates allergic inflammation and allergic inflammation-promoted cellular interactions.

The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated and allergic inflammation.

Involvement of synovial matrix degradation and angiogenesis in oxidative stress-exposed degenerative rotator cuff tears with osteoarthritis.

Background: Shoulder osteoarthritis is a gradual wearing of the articular cartilage concomitant with degenerative rotator cuff tears (RCTs). This pathologic disorder is related to inflammation, oxidative stress, and angiogenesis. Degenerative alterations may prompt production of cytokines and angiogenesis-related proteins, evoking rotator cuff diseases.

Precise Reproduction of Soft Tissue Structure around the Pontic Area Using Computer-Aided Design and Manufacturing.

Reproducing soft tissue contours around a pontic area is important for the fabrication of an esthetic prosthesis, especially in the anterior area. A gingival model that precisely replicates the soft tissue structure around the pontic area can be easily obtained by taking a pick-up impression of an interim fixed dental prosthesis. After a working cast is fabricated using the customary technique, the pick-up model is superimposed onto the working model for the pontic area using computer-aided design and manufacturing (CAD/CAM).

Phase I and phase II metabolite identification of rutaecarpine in freshly isolated hepatocytes from male Sprague-Dawley rats.

Rutaecarpine, an alkaloid originally isolated from Evodia rutaecarpa, has been used for the treatment of gastrointestinal disorders in Asia. In the present study, the phase I and phase II metabolites of rutaecarpine were investigated in freshly isolated hepatocytes from male Sprague-Dawley rats. The individual metabolites were characterized via liquid chromatography-tandem mass spectrometry.