A delayed proinflammatory response of human preadipocytes to PCB126 is dependent on the aryl hydrocarbon receptor

Abstract

Inflammation in adipose tissue is recognized as a causative factor in the development of type II diabetes. Adipocyte hypertrophy as well as bacterial and environmental factors have been implicated in causing inflammation in mature adipocytes. Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) has been associated with the development of type II diabetes. We show here that PCB126, a dioxin-like PCB, activates a robust proinflammatory state in fat cell precursors (preadipocytes). The response was found to be dependent on aryl hydrocarbon receptor (AhR) activation, although induction of the response was delayed compared to upregulation of CYP1A1, a classic AhR-responsive gene. Treatment of preadipocytes with a nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) inhibitor partially attenuated the PCB126-induced inflammatory response and partly, but not completely, ameliorated disruption of adipogenesis caused by PCB126. Our results indicate a role for PCB126 in mediating an inflammatory response through AhR in preadipocytes that interferes with adipogenesis.

http://ift.tt/2u2Q7J8

Study of chlordecone desorption from activated carbons and subsequent dechlorination by reduced cobalamin

Abstract

Since 1972, the French departments of Guadeloupe and Martinique have intensively used organochlorinated pesticides such as chlordecone (CLD) and hexachlorocyclohexane (HCH) isomers to prevent the proliferation of banana weevil (Cosmopolite sordidus). These molecules are stable in the environment, leading to a continuous contamination of soils, water, and food chain in the banana-producing areas. In these polluted areas, water treatment plants are equipped with activated carbon (AC) filters. In order to improve treatment of CLD-contaminated waters by AC, CLD adsorption and desorption kinetic studies are carried out using different ACs produced from sugar cane bagasse as adsorbents and subsequent CLD degradation is performed using reduced vitamin B12 (VB12). A GC-MS method for CLD quantification is as well optimized. This study shows that bagasse ACs are able to capture the pollutant, leading to a CLD concentration decrease from 1 to 73 μg L⁻¹, with an adsorption capacity of 162 μg mg⁻¹. Adsorption capacity increase with the temperature indicates an endothermic process. Polar solvents favor CLD desorption from ACs, suggesting hydrogen bonding between CLD and surface groups of ACs, the best solvent for chemical desorption being ethanol. Subsequent degradation of CLD in ethanol is performed using vitamin B12 reduced by either 1,4-dithiotreitol (DTT) or zerovalent zinc, leading to 90% of CLD removal and to the molecule cage structure opening for formation of a pentachloroindene intermediate product, characterized by GC MS/MS. A pathway for pentachloroindene formation from CLD is proposed.

http://ift.tt/2sKd93B

DNA mismatch repair and its many roles in eukaryotic cells

Publication date: Available online 9 July 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Dekang Liu, Guido Keijzers, Lene Juel Rasmussen
DNA mismatch repair (MMR) is an important DNA repair pathway that plays critical roles in DNA replication fidelity, mutation avoidance and genome stability, all of which contribute significantly to the viability of cells and organisms. MMR is widely-used as a diagnostic biomarker for human cancers in the clinic, and as a biomarker of cancer susceptibility in animal model systems. Prokaryotic MMR is well-characterized at the molecular and mechanistic level; however, MMR is considerably more complex in eukaryotic cells than in prokaryotic cells, and in recent years, it has become evident that MMR plays novel roles in eukaryotic cells, several of which are not yet well-defined or understood. Many MMR-deficient human cancer cells lack mutations in known human MMR genes, which strongly suggests that essential eukaryotic MMR components/cofactors remain unidentified and uncharacterized. Furthermore, the mechanism by which the eukaryotic MMR machinery discriminates between the parental (template) and the daughter (nascent) DNA strand is incompletely understood and how cells choose between the EXO1-dependent and the EXO1–independent subpathways of MMR is not known. This review summarizes recent literature on eukaryotic MMR, with emphasis on the diverse cellular roles of eukaryotic MMR proteins, the mechanism of strand discrimination and cross-talk/interactions between and co-regulation of MMR and other DNA repair pathways in eukaryotic cells. The main conclusion of the review is that MMR proteins contribute to genome stability through their ability to recognize and promote an appropriate cellular response to aberrant DNA structures, especially when they arise during DNA replication. Although the molecular mechanism of MMR in the eukaryotic cell is still not completely understood, increased used of single-molecule analyses in the future may yield new insight into these unsolved questions.



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Sonodynamic Therapy Based on Combined Use of Low Dose Administration of Epirubicin-Incorporating Drug Delivery System and Focused Ultrasound

Publication date: Available online 10 July 2017
Source:Ultrasound in Medicine & Biology
Author(s): Masanori Maeda, Yoshihiro Muragaki, Jun Okamoto, Shin Yoshizawa, Nobutaka Abe, Hidekazu Nakamoto, Hiroshi Ishii, Kenichi Kawabata, Shinichiro Umemura, Nobuhiro Nishiyama, Kazunori Kataoka, Hiroshi Iseki
Sonodynamic therapy (SDT) is currently considered as one of the promising minimally invasive treatment options for solid cancers. SDT is based on the combined use of a sonosensitizer drug and high-intensity focused ultrasound (HIFU) to produce cytotoxic reactive oxygen species (ROS) in and around neoplastic cells. Anthracycline drugs, including epirubicin (EPI), have been well known as effective sonosensitizers after interaction with focused ultrasound. Recently a new anticancer drug delivery system (DDS), NC-6300, has been developed that comprises EPI through an acid–labile hydrazone bond. In previous in vivo studies, NC-6300 showed basic drug safety and an excellent concentration property of EPI, and recently has been tested in clinical trials. For realizing minimally invasive cancer treatment, the present study demonstrated the effectiveness and feasibility of DDS-based SDT, which combined a small dose of NC-6300 and low energy of HIFU in mouse models of colon cancer and pancreatic cancer.



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Supersonic Shear Wave Imaging of the Spleen for Staging of Liver Fibrosis in Rats

Publication date: Available online 10 July 2017
Source:Ultrasound in Medicine & Biology
Author(s): Xiang-Dong Hu, Hui-Ying Geng, Lei Wang, Hu-Feng Xu, Yuan Su, Si Liang, Lin-Xue Qian
The goal of the work described here was to explore the cause of spleen stiffness (SS) in hepatic fibrogenesis and evaluate the value of SS in liver fibrosis (LF) staging. LF was induced with carbon tetrachloride (CCl4) in rats (n = 40). Supersonic shear wave imaging and contrast-enhanced ultrasound were performed to determine liver stiffness (LS), SS and splenic hemodynamics. SS, LS and free portal pressure exhibited moderate correlations with fibrosis stage (r = 0.744–0.835, p < 0.001). Time–intensity curves of contrast-enhanced ultrasound for the spleen were presented as decreasing peak intensity and slope of decrease, and increasing time to peak. Splenic sinus dilation and congestion were observed on histopathologic analysis. The area under the receiver operating characteristic curve of SS was higher than that of LS for differentiating LF stages 0–2 from stages 3–4 (Z = 2.293, p = 0.02). SS is a reliable diagnostic marker for the assessment of LF in the CCl4 model, especially for severe fibrosis. Elevated portal pressure is the cause of increasing SS.



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Automatic Identification of the Optimal Reference Frame for Segmentation and Quantification of Focal Liver Lesions in Contrast-Enhanced Ultrasound

Publication date: Available online 10 July 2017
Source:Ultrasound in Medicine & Biology
Author(s): Spyridon Bakas, Dimitrios Makris, Gordon J.A. Hunter, Cheng Fang, Paul S. Sidhu, Katerina Chatzimichail
Post-examination interpretation of contrast-enhanced ultrasound (CEUS) cineloops of focal liver lesions (FLLs) requires offline manual assessment by experienced radiologists, which is time-consuming and generates subjective results. Such assessment usually starts by manually identifying a reference frame, where FLL and healthy parenchyma are well-distinguished. This study proposes an automatic computational method to objectively identify the optimal reference frame for distinguishing and hence delineating an FLL, by statistically analyzing the temporal intensity variation across the spatially discretized ultrasonographic image. Level of confidence and clinical value of the proposed method were quantitatively evaluated on retrospective multi-institutional data (n = 64) and compared with expert interpretations. Results support the proposed method for facilitating easier, quicker and reproducible assessment of FLLs, further increasing the radiologists' confidence in diagnostic decisions. Finally, our method yields a useful training tool for radiologists, widening CEUS use in non-specialist centers, potentially leading to reduced turnaround times and lower patient anxiety and healthcare costs.



http://ift.tt/2u2ON98

Influence of external cooling on the femtosecond laser ablation of dentin

Abstract

In the present work, the influence of external cooling on the temperature rise in the tooth pulpal chamber during femtosecond laser ablation was investigated. The influence of the cooling method on the morphology and constitution of the laser-treated surfaces was studied as well. The ablation experiments were performed on dentin specimens using an Yb:KYW chirped-pulse-regenerative amplification laser system (560 fs, 1030 nm). Cavities were created by scanning the specimens at a velocity of 5 mm/s while pulsing the stationary laser beam at 1 kHz and with fluences in the range of 2–14 J/cm². The experiments were performed in air and with surface cooling by a lateral air jet and by a combination of an air jet and water irrigation. The temperature in the pulpal chamber of the tooth was measured during the laser experiments. The ablation surfaces were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The temperature rise reached 17.5 °C for the treatments performed with 14 J/cm² and without cooling, which was reduced to 10.8 ± 1.0 and 6.6 ± 2.3 °C with forced air cooling and water cooling, respectively, without significant reduction of the ablation rate. The ablation surfaces were covered by ablation debris and resolidified droplets containing mainly amorphous calcium phosphate, but the amount of redeposited debris was much lower for the water-cooled specimens. The redeposited debris could be removed by ultrasonication, revealing that the structure and constitution of the tissue remained essentially unaltered. The present results show that water cooling is mandatory for the femtosecond laser treatment of dentin, in particular, when high fluences and high pulse repetition rates are used to achieve high material removal rates.

http://ift.tt/2sZ4w9l

High-fat diet induces skeletal muscle oxidative stress in a fiber type-dependent manner in rats

Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Ricardo A. Pinho, Diane M. Sepa-Kishi, George Bikopoulos, Michelle V. Wu, Abinas Uthayakumar, Arta Mohasses, Meghan C. Hughes, Christopher G.R. Perry, Rolando B. Ceddia
This study investigated the effects of high-fat (HF) diet on parameters of oxidative stress among muscles with distinct fiber type composition and oxidative capacities. To accomplish that, male Wistar rats were fed either a low-fat standard chow (SC) or a HF diet for 8 weeks. Soleus, extensor digitorum longus (EDL), and epitrochlearis muscles were collected and mitochondrial H2O2 (mtH2O2) emission, palmitate oxidation, and gene expression and antioxidant system were measured. Chronic HF feeding enhanced fat oxidation in oxidative and glycolytic muscles. It also caused a significant reduction in mtH2O2 emission in the EDL muscle, although a tendency towards a reduction was also found in the soleus and epitrochlearis muscles. In the epitrochlearis, HF diet increased mRNA expression of the NADPH oxidase complex; however, this muscle also showed an increase in the expression of antioxidant proteins, suggesting a higher capacity to generate and buffer ROS. The soleus muscle, despite being highly oxidative, elicited H2O2 emission rates equivalent to only 20% and 35% of the values obtained for EDL and epitrochlearis muscles, respectively. Furthermore, the Epi muscle with the lowest oxidative capacity was the second highest in H2O2 emission. In conclusion, it appears that intrinsic differences related to the distribution of type I and type II fibers, rather than oxidative capacity, drove the activity of the anti- and pro-oxidant systems and determine ROS production in different skeletal muscles. This also suggests that the impact of potentially deleterious effects of ROS production on skeletal muscle metabolism/function under lipotoxic conditions is fiber type-specific.

Graphical abstract

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Involvement of Penicillium digitatum PdSUT1 in fungicide sensitivity and virulence during citrus fruit infection.

Publication date: Available online 10 July 2017
Source:Microbiological Research
Author(s): Marta de Ramón-Carbonell, Paloma Sánchez-Torres
A putative sucrose transporter PdSUT1 included in the same clade that Sut1p from Schizosaccharomyces pombe was identified in Penicillium digitatum, the major citrus postharvest pathogen. PdSUT1 gene was characterized using target gene disruption and gene overexpression. The ΔPdSUT1 mutants generated by gene elimination showed reduction in fungal virulence during citrus fruit infection assayed in mature fruit at 20°C. However, the overexpression mutants did not increased disease severity neither in the mutants coming from a high virulent nor from a low virulent P. digitatum progenitor strains.Moreover, fungicide sensitivity was affected in the deletant mutants but not in the overexpression transformants. The expression analysis of several genes involved in fungicide resistance showed an intensification of MFS transporters and a decrease of sterol demethylases transcriptional abundance in the ΔPdSUT1 mutants compare to the parental wild type strain.PdSUT1 appear not to be directly involved in fungicide resistance although can affect the gene expression of fungicide related genes. These results indicate that PdSUT1 contribute to P. digitatum fungal virulence and influence fungicide sensitivity through carbohydrate uptake and MFS transporters gene activation.



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Influence of Non-Measurable Disease on Progression-Free Survival in Patients with Metastatic Breast Cancer

Publication date: Available online 11 July 2017
Source:Cancer Treatment Reviews
Author(s): Hadar Goldvaser, Domen Ribnikar, Rouhi Fazelzad, Bostjan Seruga, Arnoud J. Templeton, Alberto Ocana, Eitan Amir
BackgroundThe presence of non-measurable disease is common in metastatic breast cancer. It is unknown whether treatment effect on progression free survival (PFS) is consistent among patients with measurable and non-measurable disease.MethodsA systematic literature search identified phase III randomized controlled trials (RCTs) in metastatic breast cancer that reported outcomes in patients with non-measurable and measurable disease. Hazard ratios (HRs) and 95% confidence intervals were computed to compare the individual trial treatment effect on PFS in non-measurable versus measurable disease. Analyses were repeated for bone-only compared to non-bone-only disease and based on drug mechanism of action.ResultsAmong 82 RCTs that enrolled patients with non-measurable disease, data were available from 16 trials comprising 8516 patients. Treatment effect on PFS was similar in patients with non-measurable and measurable disease (HR for intra-study comparison = 1.01, p=0.82). However, compared to non-bone-only disease, a significantly greater effect on PFS was seen in those with bone-only disease (HR 0.83, p=0.03). Compared to patients with measurable disease, there was a greater effect on PFS in those with non-measurable disease in RCTs of signal transduction inhibitors and endocrine therapy (HR 0.74, p=0.01) and a lesser effect on PFS in RCTs of antiangiogenic drugs (HR 1.34, p=0.02). Comparable effect on PFS was shown in RCTs evaluating endocrine therapy (HR 1.13, p=0.23) and chemotherapy (HR 0.73, p=0.22).ConclusionsThere is variability in treatment effect on PFS in patients with measurable and non-measurable disease, especially those with bone-only disease. Standardization of PFS determination in these patients is warranted.



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Preinvasive disease of the airway

Publication date: July 2017
Source:Cancer Treatment Reviews, Volume 58
Author(s): Ricky M. Thakrar, Adam Pennycuick, Elaine Borg, Sam M. Janes
Squamous cell carcinoma of the lung arises from preinvasive progenitors in the central airways. The archetypal model appears to be a stepwise morphological progression until there is invasion of the basement membrane. However, not every lesion appears to follow this course and many individuals can have stable disease, or indeed regress to normal epithelium. From our increased understanding of the molecular pathology it is becoming apparent that the respiratory epithelium accumulates progressive genetic and epigenetic insults in response to carcinogens. Still, little is known about how to predict those 'at risk' of progression, and it is likely that in the future molecular signatures will underpin prediction models of developing invasive lung cancer. Currently, autofluorescence bronchoscopy gives us the ability to follow the natural history of these lesions, with the prospect that detecting and treating lesions early may improve survival. However, treatment remains controversial, and radical therapies are offered to individuals with carcinoma in situ who may never develop invasive cancer. This has paved the way for the use of minimally invasive bronchoscopic treatments, which, while apparently effective, have not been tested in randomised controlled trials. In this paper we describe the known biology and natural history of preinvasive lesions and review the current treatment strategies.



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Glial-associated changes in the cerebral cortex after collagenase-induced intracerebral hemorrhage in the rat striatum

Publication date: Available online 10 July 2017
Source:Brain Research Bulletin
Author(s): J.D. Neves, D. Aristimunha, A.F. Vizuete, F. Nicola, C. Vanzela, L. Petenuzzo, R.G. Mestriner, E.F. Sanches, C.A. Gonçalves, C.A. Netto
Striatum and the cerebral cortex are regions susceptible to secondary injury after intracerebral hemorrhage (ICH) and glial cells in tissue adjacent to the hematoma may modulate cellular vulnerability after brain damage. Nonetheless, while the glial- associated changes occurring in the cerebral cortex after ICH may be important in maximizing brain recovery, they are not fully understood. The aim of this study was to evaluate the temporal profile of glial-associated changes in the cerebral cortex after ICH. First, the motor consequences of ICH and its relation to the lesion volume were analyzed. Secondly, glial cell proportion (GFAP+ and S100B+ astrocytes, CD11+ microglia) in the ipsilesional sensorimotor cortex and striatum, using flow cytometry were evaluated. ELISA was used to measure GFAP and S100B content in these structures as well as S100B levels in serum and cerebral spinal fluid. Main results revealed that ICH induced a delayed increase in GFAP+ cells in the sensorimotor cortex, as compared to the striatum, although the pattern of GFAP expression was similar in both structures. Interestingly, the time-curve patterns of both S100B and CD11+ microglial cells differed between the cortex and striatum. Altogether, these results suggest a different dynamics of glial-associated changes in the cerebral cortex, suggesting it is a vulnerable structure and undergoes an independent secondary process of reactive glial plasticity following intracerebral hemorrhage.



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The effect of CXCR2 inhibition on seizure activity in the pilocarpine epilepsy mouse model

Publication date: Available online 10 July 2017
Source:Brain Research Bulletin
Author(s): Tao Xu, Xinyuan Yu, Teng Wang, Ying Liu, Xi Liu, Shu Ou, Yangmei Chen
C-X-C motif chemokine receptor 2 (CXCR2) is one of the most well characterized chemokine receptors and is a potential target for treating brain pathologies involving inflammatory processes, including epilepsy. However, the role of CXCR2 in epilepsy has not been investigated, and whether CXCR2 modulates seizure activity in temporal lobe epilepsy (TLE) remains unknown. In this study, we aimed to determine the potential role of CXCR2 in intractable TLE patients and in pilocarpine-induced epileptic mice. Here, through Western blotting and semi-quantitative immunohistochemistry, we detected that CXCR2 protein expression was up-regulated (by nearly 50%) in the temporal neocortex of TLE patients and in the hippocampus and adjacent temporal cortex of pilocarpine mice model. Double-label immunofluorescence and immunohistochemical analysis indicated that CXCR2 was expressed in neurons. To investigate the effect of the CXCR2 selective antagonist SB225002 on seizure activity, SB225002 was i.p. administered during the latency window of spontaneous recurrent seizures (SRSs). This treatment increased (by nearly 40%) the latency of SRSs and reduced (by nearly 50%) the frequency of SRSs during the chronic period of epilepsy. This study suggests that CXCR2 plays a critical role in modifying epileptic seizure activity and that CXCR2 blockade could be a potential molecular therapeutic target for epilepsy.



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Unusual presentation of primary cutaneous follicle centre B-Cell Lymphoma (PC-FCL) of the nose

Primary Cutaneous Follicle Center B-cell Lymphoma (PC-FCL) is an indolent lymphoma with progressive growth and rare dissemination to extracutaneous sites and usually affects the skin of the scalp, forehead, and trunk. PC-FCL clinically mimicking other dermatologic diseases are extremely rare but could hinder a correct diagnosis. In this experimental work we describe two unusual cases of follicle centre B-Cell Lymphoma (PC-FCL) of the nose. The divulgation of such cases could assist clinicians in the differential diagnosis of nodular lesions of the nose.

http://ift.tt/2uckbST

EXO1 suppresses double-strand break induced homologous recombination between diverged sequences in mammalian cells.

Publication date: Available online 10 July 2017
Source:DNA Repair
Author(s): Chun-Chin Chen, Elena Avdievich, Yongwei Zhang, Yu Zhang, Kaichun Wei, Kyeryoung Lee, Winfried Edelmann, Maria Jasin, Jeannine R. LaRocque
DNA double-strand breaks (DSBs) can be repaired through several mechanisms, including homologous recombination (HR). While HR between identical sequences is robust in mammalian cells, HR between diverged sequences is suppressed by DNA mismatch-repair (MMR) components such as MSH2. Exonuclease I (EXO1) interacts with the MMR machinery and has been proposed to act downstream of the mismatch recognition proteins in mismatch correction. EXO1 has also been shown to participate in extensive DSB end resection, an initial step in the HR pathway. To assess the contribution of EXO1 to HR in mammalian cells, DSB-inducible reporters were introduced into Exo1^−/− mouse embryonic stem cells, including a novel GFP reporter containing several silent polymorphisms to monitor HR between diverged sequences. Compared to HR between identical sequences which was not clearly affected, HR between diverged sequences was substantially increased in Exo1^−/− cells although to a lesser extent than seen in Msh2^−/− cells. Thus, like canonical MMR proteins, EXO1 can restrain aberrant HR events between diverged sequence elements in the genome.



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An Unintended Consequence of the 21st-Century Cures Act for Patients With Heart Failure.

Author: Gilstrap, Lauren G. MD; MPH; DeFilippis, Ersilia M. MD; Stevenson, Lynne W. MD

Page: 123-125

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Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

Author: Merghani, Ahmed MD; Maestrini, Viviana PhD; Rosmini, Stefania MD; Cox, Andrew T. MD; Dhutia, Harshil MD; Bastiaenan, Rachel PhD; David, Sarojini MD; Yeo, Tee Joo MD; Narain, Rajay MD; Malhotra, Aneil MD; Papadakis, Michael MD; Wilson, Mathew G. PhD; Tome, Maite MD; AlFakih, Khaled MD; Moon, James C. MD; Sharma, Sanjay MD

Page: 126-137

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Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes.

Author: Aengevaeren, Vincent L. MD; Mosterd, Arend MD, PhD; Braber, Thijs L. MD; Prakken, Niek H.J. MD, PhD; Doevendans, Pieter A. MD, PhD; Grobbee, Diederick E. MD, PhD; Thompson, Paul D. MD; Eijsvogels, Thijs M.H. PhD *; Velthuis, Birgitta K. MD, PhD *

Page: 138-148

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Coronary Artery Calcification Among Endurance Athletes: "Hearts of Stone".

Author: Baggish, Aaron L. MD; Levine, Benjamin D. MD

Page: 149-151

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Black-White Differences in Incident Fatal, Nonfatal, and Total Coronary Heart Disease.

Author: Colantonio, Lisandro D. MD, MSc, PhD; Gamboa, Christopher M. MPH; Richman, Joshua S. MD, PhD; Levitan, Emily B. ScD; Soliman, Elsayed Z. MD, MSc, MS; Howard, George DrPH; Safford, Monika M. MD

Page: 152-166

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