Octocrylene is a common sun filter ingredient used to protect the skin from damaging UV rays. Benzophenone is an impurity found in formulations containing octocrylene. [C]-Benzophenone was spiked (0.
View Article and Find Full Text PDFObjective: Significant research and regulatory attention have been focussed on the potential for some ultraviolet filters (UVFs) to rinse off from beachgoers' skin into seawater leading to exposure to sea life, especially coral reefs. The amount of UVFs potentially rinsed from skin during recreational beach activities has not been well studied, leading to uncertainty about the potential magnitude of aquatic UVF exposure due to changes in sunscreen use patterns. This study quantifies rinse-off of UVFs in sunscreen from skin into synthetic seawater and identifies differences in rinse-off quantity due to formulation type with a goal of informing future modelling efforts aimed at estimating UVF exposure to sea life associated with recreational activities at the beach.
View Article and Find Full Text PDFTGFβ is a pleiotropic cytokine that may have both tumor inhibiting and tumor promoting properties, depending on tissue and cellular context. Emerging data support a role for TGFβ in suppression of antitumor immunity. Here we show that SAR439459, a pan-TGFβ neutralizing antibody, inhibits all active isoforms of human and murine TGFβ, blocks TGFβ-mediated pSMAD signaling, and TGFβ-mediated suppression of T cells and NK cells.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2020
N-substituted azaindoles were discovered as potent pan-PIM inhibitors. Lead optimization, guided by structure and focused on physico-chemical properties allowed us to solve inherent hERG and permeability liabilities, and provided compound 27, which subsequently impacted KG-1 tumor growth in a mouse model.
View Article and Find Full Text PDFN-substituted azaindoles were discovered as promising pan-PIM inhibitors. Lead optimization is described en route toward the identification of a clinical candidate. Modulation of physico-chemical properties allowed to solve inherent hERG and permeability liabilities.
View Article and Find Full Text PDFPolyglycerol (PG) is a well-known cosmetic ingredient and important precursor for the synthesis of a variety of cosmetic ingredients, such as surfactants, emulsifiers, and conditioning agents for hair and skin. When derived from renewable resources, PG can provide a more sustainable platform for the development of new ingredients with improved performance in cosmetic applications. This paper will discuss recent advances in the utilization of bio-based PG ingredients as alternatives to traditional ethoxylate chemistries for mild nonionic surfactants, substantive humectants, and micellar thickeners.
View Article and Find Full Text PDFObjective: Establishing an effective humoral immunity is an important host defense mechanism in intestinal mucosa. T follicular helper (Tfh) cells are a spectrum of CXCR5 expressing T helper cells that induce antigen-specific B cell differentiation. Because the differentiation of T helper cells is largely regulated by innate immunity, we addressed whether TRIF signaling regulates Tfh cell differentiation and its ability to trigger humoral immune responses in the intestine.
View Article and Find Full Text PDFBioorg Med Chem Lett
February 2016
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase belonging to the insulin receptor superfamily. Expression of ALK in normal human tissues is only found in a subset of neural cells, however it is involved in the genesis of several cancers through genetic aberrations involving translocation of the kinase domain with multiple fusion partners (e.g.
View Article and Find Full Text PDFUnlabelled: Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Herein, we report the first preclinical evaluation of the next-generation ALK TKI, ceritinib (LDK378), in the setting of crizotinib resistance. An interrogation of in vitro and in vivo models of acquired resistance to crizotinib, including cell lines established from biopsies of patients with crizotinib-resistant NSCLC, revealed that ceritinib potently overcomes crizotinib-resistant mutations.
View Article and Find Full Text PDFObjective. The objective of this research was to evaluate the caries control potential of a new fluoride mouthrinse that also contained antimicrobial agents and a biofilm disrupting agent using different in vitro models. Methods.
View Article and Find Full Text PDFMultisite longitudinal neuroimaging designs are used to identify differential brain structural change associated with onset or progression of disease. The reliability of neuroanatomical measurements over time and across sites is a crucial aspect of power in such studies. Prior work has found that while within-site reliabilities of neuroanatomical measurements are excellent, between-site reliability is generally more modest.
View Article and Find Full Text PDFThe synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.
View Article and Find Full Text PDFEur Arch Psychiatry Clin Neurosci
September 2013
Via influencing brain plasticity, aerobic exercise could contribute to the treatment of schizophrenia patients. As previously shown, physical exercise increases hippocampus volume and improves short-term memory. We now investigated gray matter density and brain surface expansion in this sample using MRI-based cortical pattern matching methods.
View Article and Find Full Text PDFSpontaneous degradation of bottlebrush macromolecules on aqueous substrates was monitored by atomic force microscopy. Scission of C ─ C covalent bonds in the brush backbone occurred due to steric repulsion between the adsorbed side chains, which generated bond tension on the order of several nano-Newtons. Unlike conventional chemical reactions, the rate of bond scission was shown to decrease with temperature.
View Article and Find Full Text PDFBackground: Although sleepiness and fatigue are common symptoms in depressed patients, the relationships among sleepiness, fatigue and treatment of depression have not been fully elucidated. The main objective of this study was to investigate the therapeutic effects of a sedating antidepressant on sleepiness and fatigue in patients with depression.
Methods: Forty-two depressed patients, who met DSM-IV diagnostic criteria, and 32 matched healthy controls participated in the baseline measurements.
Lactobacillus johnsonii (Ljo) N6.2 has been shown to mitigate the development of type 1 diabetes when administered to diabetes-prone rats. The specific mechanisms underlying this observed response remain under investigation.
View Article and Find Full Text PDFSpreading of homogeneous mixtures of bottle-brush and linear macromolecules of poly(n-butylacrylate) on a solid substrate has been monitored on the molecular scale by atomic force microscopy. Despite the nearly identical chemical composition and similar molecular weight, brush-like macromolecules move markedly slower than linear chains. Moreover, smaller bottle-brushes have been shown to flow faster than the larger bottle-brushes, resulting in fractionation of the macromolecules along the spreading direction.
View Article and Find Full Text PDFBackground: The continued presence of a primate antibody-mediated response to cells and organs from alpha1,3-galactosyltransferase gene-knockout (GTKO) pigs indicates that there may be antigens other than Gal alpha 1,3Gal (alpha Gal) against which primates have xenoreactive antibodies. Human and baboon sera were tested for reactivity against a panel of saccharides that might be potential antigen targets for natural anti-non-alpha Gal antibodies.
Methods: Human sera (n = 16) and baboon sera (n = 15) of all ABO blood types were tested using an enzyme-linked immunoadsorbent assay for binding of IgM and IgG to a panel of synthetic polyacrylamide-linked saccharides (n = 15).
Adsorption-induced degradation of brushlike macromolecules was monitored through molecular imaging by atomic force microscopy. The rate constant for C-C bond cleavage was shown to be extremely sensitive to the substrate surface energy. A few percent increase in the surface energy from 69.
View Article and Find Full Text PDFThe generalization of the Flory theorem for structurally asymmetric mixtures was derived and tested by direct visualization of conformational transformations of brushlike macromolecules embedded in a melt of linear chains. Swelling of a brush molecule was shown to be controlled not only by the degree of polymerization (DP) of the surrounding linear chains, N(B), but also by the DP of the brush's side chains, N, which determines the structural asymmetry of the mixed species. The boundaries of the swelling region were established by scaling analysis as N(2) < N (B) < N (A)/N, where N (A) is the degree of polymerization of the brush backbone.
View Article and Find Full Text PDFCovalent carbon-carbon bonds are hard to break. Their strength is evident in the hardness of diamonds and tensile strength of polymeric fibres; on the single-molecule level, it manifests itself in the need for forces of several nanonewtons to extend and mechanically rupture one bond. Such forces have been generated using extensional flow, ultrasonic irradiation, receding meniscus and by directly stretching a single molecule with nanoprobes.
View Article and Find Full Text PDFObjective: This study aimed to characterize the effects of mirtazapine on polysomnographic sleep, especially slow wave sleep (SWS) and rapid eye movement (REM) sleep, as well as its effects on clinical symptoms in patients with major depressive disorder (MDD).
Method: Sixteen MDD patients were treated with mirtazapine 30 mg taken 30 minutes before bedtime. Polysomnographic and subjective sleep, as well as other clinical data, were collected at baseline and on Days or Nights 2, 9, 16, 30, and 58 during treatment.
Background: Poor oral health has been reported among various psychiatric populations. Little is known regarding the oral health among psychiatric patients in Asia.
Aims: To examine the oral health status of a group of Chinese psychiatric in-patients in a long-term rehabilitation facility.
Introduction: The purpose of the study was to evaluate a recently introduced aesthetic restorative system in respect of: Presentation and organisation of the package. Its handling characteristics. Its polishability.
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