Atractylone, an active constituent of KMP6, attenuates allergic inflammation on allergic rhinitis in vitro and in vivo models

Publication date: October 2016
Source:Molecular Immunology, Volume 78
Author(s): Hee-Yun Kim, Sun-Young Nam, Sung-Yeoun Hwang, Hyung-Min Kim, Hyun-Ja Jeong
KMP6 (Pyeongwee-San) is a Korean Medicine used to treat gastrointestinal disorders. Recently, we reported KMP6 had beneficial effects on allergic inflammatory diseases. The aim of this study was to evaluate the effects of atractylone (Atr), a constituent of KMP6, on allergic rhinitis (AR) and to identify the mechanism responsible for these effects. The anti-allergic inflammatory effects of Atr were evaluated on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells and in an ovalbumin (OVA)-induced AR animal model using Western blotting, quantitative real-time PCR, ELISA, and immunohistochemistry methods. In HMC-1 cells, Atr and KMP6 attenuated PMACI-caused proinflammatory cytokine production and mRNA expression. We found that PMACI induced caspase-1/nuclear factor (NF)-κB/mitogen activated protein kinases (MAPKs) activation. PMACI-caused caspase-1/NF-κB/MAPKs activations were attenuated by Atr and KMP6. In AR animal model, Atr and KMP6 reduced AR clinical symptoms and biomarkers including rub scores, total IgE, histamine, prostaglandin D2, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor-α, cyclooxygenase-2, intercellular adhesion molecule-1, and macrophage inflammatory protein-2. In addition, Atr and KMP6 attenuated eosinophils and mast cells invasions into nasal mucosa tissues and diminished mast cell-derived caspase-1 activation. These results indicate that Atr is an active constituent of KMP6 and a potential therapeutic agent for AR.



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Patient Experiences of Life Years After Severe Civilian Lower Extremity Trauma With Vascular Injury

Publication date: Available online 13 September 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): K. Bernhoff, M. Björck, J. Larsson, E. Jangland
ObjectiveSevere lower limb trauma with arterial injury is often devastating for the individual. Many studies describe how to manage these injuries when they occur. Short-term functional outcome is quite well described, but the patients are often young, and their suffering is physical, mental, and social from a lifelong perspective. The aim of this study was to report patient experiences of their lives several years after their accidents, and to explore mechanisms of how to improve management.MethodThe Swedvasc registry was searched for participants from 1987 to 2011, living in the region of Uppsala, Sweden. Some amputated participants were added from the Walking Rehabilitation Center. There were five reconstructed patients with an intact limb, and three with amputations. In depth interviews were conducted and systematically analyzed, using A Giorgi's descriptive phenomenological method.ResultsEight patients participated, five with reconstructed and three with amputated limbs. Life affecting functional impairments were described by all patients. The patients undergoing amputation had received more structured follow up and support through the Walking Rehabilitation Center. The satisfaction with the cosmetic result was poorer than expected. All patients had developed strategies of how to cope with their impairments and stated they now lived "normal lives."ConclusionsDespite substantial physical, psychological, and cosmetic impairments years after severe lower limb trauma, the participants described life as "normal" and mainly satisfactory. Transition to the new situation could have been facilitated by more frequent and continuous follow up after discharge from hospital, in particular among the non-amputated patients who tend to be lost to follow up. Findings also indicate that family members have to be acknowledged, strengthened, and supported.



http://ift.tt/2cIjRkc

Deep Rtms for Neuropsychiatric Symptoms of Huntington's Disease: Case Report

Publication date: Available online 13 September 2016
Source:Brain Stimulation
Author(s): Molly Davis, Angela Phillips, Aron Tendler, Angela Oberdeck




http://ift.tt/2cdUcjK

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum Reproducibly Improves Symptoms of Body Dysmorphic Disorder

Publication date: Available online 13 September 2016
Source:Brain Stimulation
Author(s): Juan Carlos Baldermann, Sina Kohl, Veerle Visser-Vandewalle, Martin Klehr, Daniel Huys, Jens Kuhn




http://ift.tt/2cvWiZB

The Difficult Journey from Genome-wide Association Studies to Pathophysiology: The Melatonin Receptor 1B (MT2) Paradigm

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Amélie Bonnefond, Angeliki Karamitri, Ralf Jockers, Philippe Froguel




http://ift.tt/2cMzPIB

Never Waste a Good Crisis: Confronting Reproducibility in Translational Research

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Daniel J. Drucker
The lack of reproducibility of preclinical experimentation has implications for sustaining trust in and ensuring the viability and funding of the academic research enterprise. Here I identify problematic behaviors and practices and suggest solutions to enhance reproducibility in translational research.

Teaser

Reproducibility challenges in preclinical research threaten the integrity and viability of our research enterprise. Here Drucker discusses the complexity of methodological, technical, and ethical issues contributing to lack of reproducibility and suggests options for discussion that may enhance the reproducibility and translational relevance of preclinical studies.


http://ift.tt/2cDNTas

Physiological Regulation: How It Really Works

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Douglas S. Ramsay, Stephen C. Woods
Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.

Teaser

Contrary to dogma, much physiological regulation utilizes learning from past experience to make responses that preemptively and effectively neutralize anticipated regulatory challenges. Understanding physiological regulation therefore requires expanding explanatory models beyond homeostasis and allostasis to emphasize the prominence of conditioning.


http://ift.tt/2cMyxgS

Pharma and Academia: What We Have Here Is a Failure to Communicate

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Morris J. Birnbaum
In recent years, there has been substantial interest in the potential value of collaboration between academia and the pharmaceutical industry. In this Crosstalk, I discuss obstacles to these relationships being optimally productive.

Teaser

In recent years, there has been substantial interest in the potential value of collaboration between academia and the pharmaceutical industry. In this Crosstalk, Birnbaum discusses obstacles to these relationships being optimally productive.


http://ift.tt/2cDNbK0

The Irony of Tumor-Induced Inflammation

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Florian R. Greten
Increased dietary iron intake and elevated systemic iron levels are associated with increased cancer risk. In this issue, Xue et al. (2016) have identified an unexpected link between intracellular iron accumulation and pro-inflammatory signaling that provides, at least in part, a molecular explanation for the tumor-promoting effects of iron.

Teaser

Increased dietary iron intake and elevated systemic iron levels are associated with increased cancer risk. In this issue, Xue et al. have identified an unexpected link between intracellular iron accumulation and pro-inflammatory signaling that provides, at least in part, a molecular explanation for the tumor-promoting effects of iron.


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Weeding Out the Bad Apples

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Nikla Emambokus, Anne Granger




http://ift.tt/2cDN3dN

Beige Communication through Gap Junctions and Adaption by Autophagy

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Sven Enerbäck
How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 43 (Cx43) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.

Teaser

How thermogenic stimuli activate and control beige adipocytes is not fully understood. In this issue, Zhu et al. (2016) and Altshuler-Keylin et al. (2016) provide insights into these important issues by demonstrating roles for connexin 45 (Cx45) atg5 and atg12 in signal propagation and phenotypic adaptation in beige adipocytes.


http://ift.tt/2cMzQMJ

Specialized Hub Beta Cells Trade Maximal Insulin Production for Perfect Timing

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Jelena Kolic, James D. Johnson
The pulsatility of insulin release is disturbed early in type 2 diabetes, but it is not clear whether specialized pacemaker cells drive islet oscillations. In this issue of Cell Metabolism, Johnston et al. (2016) show that specialized hubs, identified as 1%–10% of beta cells with more active mitochondria and less insulin, synchronize beta cell oscillations.

Teaser

The pulsatility of insulin release is disturbed early in type 2 diabetes, but it is not clear whether specialized pacemaker cells drive islet oscillations. In this issue of Cell Metabolism, Johnston et al. (2016) show that specialized "hubs," identified as 1%–10% of beta cells with more active mitochondria and less insulin, synchronize beta cell oscillations.


http://ift.tt/2cDNDYY

Fueling Performance: Ketones Enter the Mix

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Brendan Egan, Dominic P. D'Agostino
Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. (2016) demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.

Teaser

Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.


http://ift.tt/2cMyQbI

Mitochondrial Transfer from Astrocytes to Neurons following Ischemic Insult: Guilt by Association?

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Michael V. Berridge, Remy T. Schneider, Melanie J. McConnell
Intercellular mitochondrial transfer has been shown in tumor models, following lung injury and in xenotransplants of leukemic cells, but trafficking between cells in the brain remains unexplored. A suggestion that mitochondria move from astrocytes to neurons in a model of ischemia in a recent article in Nature by Hayakawa et al. (2016) should be interpreted with caution.

Teaser

Intercellular mitochondrial transfer has been shown in tumor models, following lung injury and in xenotransplants of leukemic cells, but trafficking between cells in the brain remains unexplored. A suggestion that mitochondria move from astrocytes to neurons in a model of ischemia in a recent article in Nature by Hayakawa et al. (2016) should be interpreted with caution.


http://ift.tt/2cDNXH7

Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Harding H. Luan, Ruslan Medzhitov
Itaconate is a newly discovered mammalian metabolite bearing significant implications for our understanding of cellular immunometabolism and antimicrobial defense. Here, we explore recent findings regarding the role of itaconate in the innate immune response and highlight the emerging principle that metabolites can have distinct immunological functions independent of bioenergetics.

Teaser

In this Minireview, Luan and Medzhitov discuss the newly discovered mammalian metabolite itaconate as both a regulator and effector of immunity. More generally, they explore the emerging concept that metabolites have distinct immunological functions that could be employed as antimicrobial therapeutics.


http://ift.tt/2cMBn5k

Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Yi Zhu, Yong Gao, Caroline Tao, Mengle Shao, Shangang Zhao, Wei Huang, Ting Yao, Joshua A. Johnson, Tiemin Liu, Aaron M. Cypess, Olga Gupta, William L. Holland, Rana K. Gupta, David C. Spray, Herbert B. Tanowitz, Lei Cao, Matthew D. Lynes, Yu-Hua Tseng, Joel K. Elmquist, Kevin W. Williams, Hua V. Lin, Philipp E. Scherer
"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue.

Graphical abstract

Teaser

Cold activates the "beiging" of white adipocytes through a sympathetic neuronal signal. White adipose tissue, however, is sparsely innervated. Here, Zhu et al. (2016) show that connexin 43 (Cx43) cell-to-cell gap junction channels are necessary for the propagation of sympathetic signals leading to the beiging of white adipocyte clusters.


http://ift.tt/2cDNbtu

Sex and Gender: Critical Variables in Pre-Clinical and Clinical Medical Research

Publication date: 13 September 2016
Source:Cell Metabolism, Volume 24, Issue 3
Author(s): Eugenia Morselli, Aaron P. Frank, Roberta S. Santos, Luciana A. Fátima, Biff F. Palmer, Deborah J. Clegg




http://ift.tt/2cDOGIq

MATERNAL EXPOSURE TO BISPHENOL-A DURING PREGNANCY INCREASES PANCREATIC Β-CELL GROWTH DURING EARLY LIFE IN MALE MICE OFFSPRING

Endocrinology, Early Release.


http://ift.tt/2cYRYGG

Ghrelin octanoylation is completely stabilized in biological samples by alkyl fluorophosphonates

Endocrinology, Early Release.


http://ift.tt/2cIkutK

Caregivers’ perception of factors associated with a healthy diet among people with intellectual disability living in community residences: A Concept mapping method

Publication date: December 2016
Source:Research in Developmental Disabilities, Volume 59
Author(s): Marte Pilskog Ruud, Ruth Kjærsti Raanaas, Mona Bjelland
BackgroundMany people with intellectual disabilities (ID) living in community-based residences have been found to have unhealthy diet and weight disturbances. In Norway, a majority of people with ID live in such residences.AimsThe aim of the study was to examine factors affecting the caregivers' opportunity to promote a healthy diet among the residents.Methods and proceduresA concept mapping methodology was adopted, including group-based brainstorming, idea synthesising, sorting, rating and analysis of the results. Informants were caregivers in four different community residences for people with mild to moderate ID in the southeast of Norway. A total of 13 informants were recruited (12 females and 1 male), and 10 informants completed two sessions.ResultsEight clusters were identified as affecting the caregivers' ability to promote a healthy diet: "Availability and accessibility", "Guidance and autonomy", "Competence among staff", "Planning and involvement", "Customization", "External conditions affecting staff", "Legislation, rules and structure" and "Everyday challenges", each including both barriers and facilitators.Conclusions and implicationsMultiple factors affect the caregivers' ability to promote a healthy diet. Caregivers' opportunity to promote a healthy diet is complex. Availability and accessibility of healthy food is crucial, but a healthy diet also requires time and competence among the caregivers.

Graphical abstract

http://ift.tt/2c7ZXfM