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tolerance mechanism

Thomas Morville, Tine Dohlmann, Anja B Kuhlman, Tine Monberg, Mimmi Torp, Bolette Hartmann, Jens J Holst, Steen Larsen, Jørn W Helge, Flemming Dela
Background Statins are widely used to lower cholesterol concentrations in both primary and secondary prevention of cardiovascular disease. The treatment increases the risk of muscle pain (myalgia) and of type 2 diabetes. However, the underlying mechanisms remain disputed. Methods We investigated whether statin induced myalgia is coupled to impaired glucose homeostasis using oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT) and the hyperinsulinemic euglycemic clamp. We performed a cross-sectional study of statin users without CVD (primary prevention) stratified into a statin myalgic (M; n=25) and a non-myalgic (NM; n=39) group as well as a control group (C; n=20) consisting of non-statin users...
December 5, 2018: Diabetes/metabolism Research and Reviews
Hesheng Liu, Xiangyang Qi, Keke Yu, Anjie Lu, Kaifeng Lin, Jiajing Zhu, Min Zhang, Zhida Sun
Previous studies suggested the anti-diabetic effect of mogrosides in type 1 diabetes. To evaluate the potential effect of mogrosides in type 2 diabetes, we herein investigated the hypoglycemic and hypolipidemic effects and the underlying mechanism of mogroside-rich extract (MGE) using a high-fat diet in combination with streptozotocin (STZ)-induced diabetic model. MGE feeding for 5 weeks did not result in any obvious impact on the body weight and energy intake, but caused a moderate decrease of organ index in diabetic mice...
December 5, 2018: Food & Function
Vladimir Elisashvili, Eva Kachlishvili, Michael L Chikindas
Spore-forming probiotic bacteria have received a wide and constantly increasing scientific and commercial interest. Among them, Bacillus species are the most studied and well-characterized Gram-positive bacteria. The use of bacilli as probiotic products is expanding especially rapidly due to their inherent ability to form endospores with unique survivability and tolerance to extreme environments and to produce a large number of valuable metabolites coupled with their bio-therapeutic potential demonstrating immune stimulation, antimicrobial activities and competitive exclusion...
December 5, 2018: Probiotics and Antimicrobial Proteins
Joseph Rocco, John W Mellors, Bernard Jc Macatangay
Despite significant advances in the understanding of HIV-1 infection, a cure remains out of reach. This is, in part, due to a long-lived HIV-1 reservoir in resting CD4+ T cells, which do not express viral antigens, and thus are invisible to the immune system. These latently infected cells carry replication-competent proviruses and can cause rebound viraemia if antiretrovirals are interrupted. Characterising this HIV-1 reservoir is a challenging task, requiring identification of CD4+ T cell subsets carrying intact proviruses, as well as defining their distribution within the body...
October 1, 2018: Journal of Virus Eradication
Adugna Abdi Woldesemayat, Monde Ntwasa
Drought alone or in combination with other stresses forms the major crop production constraint worldwide. Sorghum, one of the most important cereal crops is affected by drought alone or in combination with co-occurring stresses; notwithstanding, sorghum has evolved adaptive responses to combined stresses. Furthermore, an impressive number of sorghum genes have been investigated for drought tolerance. However, the molecular mechanism underling drought response remains poorly understood. We employed a systems biology approach to elucidate regulatory and broad functional features of these genes...
2018: Frontiers in Genetics
Tim Kampowski, Sven Demandt, Simon Poppinga, Thomas Speck
Resurrection plants have fascinated scientists since centuries as they can fully recover from cellular water contents below 10%, concomitantly showing remarkable leaf folding motions. While physiological adaptations have been meticulously investigated, the understanding of structural and mechanical adaptations of this phenomenon is scarce. Using imaging and bending techniques during dehydration-rehydration experiments, morphological, anatomical, and biomechanical properties of desiccation-tolerant Ramonda myconi are examined, and selected structural adaptations are compared to those of homoiohydrous Monophyllaea horsfieldii (both Gesneriaceae)...
2018: Frontiers in Plant Science
Jie-Jun Xi, Hong-Yu Chen, Wan-Peng Bai, Rong-Chen Yang, Pei-Zhi Yang, Ru-Jin Chen, Tian-Ming Hu, Suo-Min Wang
Understanding the unusual physiological mechanisms that enable drought tolerance in xerophytes will be of considerable benefit because of the potential to identify novel and key genetic elements for future crop improvements. These plants are interesting because they are well-adapted for life in arid zones; Zygophyllum xanthoxylum , for example, is a typical xerophytic shrub that inhabits central Asian deserts, accumulating substantial levels of sodium (Na+ ) in its succulent leaves while growing in soils that contain very low levels of this ion...
2018: Frontiers in Plant Science
Liisi Raam, Epp Kaleviste, Marina Šunina, Helen Vaher, Mario Saare, Ele Prans, Maire Pihlap, Kristi Abram, Maire Karelson, Pärt Peterson, Ana Rebane, Kai Kisand, Külli Kingo
Vitiligo is a chronic multifactorial depigmentation disorder characterized by the destruction and functional loss of melanocytes. Although a direct cytotoxic T cell attack is thought to be responsible for melanocyte damage, the events leading to the loss of self-tolerance toward melanocytic antigens are not understood. This research aimed to identify novel cellular and molecular factors that participate in vitiligo pathogenesis through the application of gene expression and immunofluorescence analysis of skin biopsy samples along with immunophenotyping of circulating cells...
2018: Frontiers in Immunology
Chunzhao Zhao, Omar Zayed, Zheping Yu, Wei Jiang, Peipei Zhu, Chuan-Chih Hsu, Lingrui Zhang, W Andy Tao, Rosa Lozano-Durán, Jian-Kang Zhu
The perception and relay of cell-wall signals are critical for plants to regulate growth and stress responses, but the underlying mechanisms are poorly understood. We found that the cell-wall leucine-rich repeat extensins (LRX) 3/4/5 are critical for plant salt tolerance in Arabidopsis The LRXs physically associate with the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23, which in turn interact with the plasma membrane-localized receptor-like protein kinase FERONIA (FER). The lrx345 triple mutant as well as fer mutant plants display retarded growth and salt hypersensitivity, which are mimicked by overexpression of RALF22 / 23 Salt stress promotes S1P protease-dependent release of mature RALF22 peptides...
December 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
Aditi Varthaman, Sébastien Lacroix-Desmazes
Therapeutic factor VIII presents with elevated immunogenicity. Despite intensive research in the last decades, the reasons for which 5-30% of patients with hemophilia A (encompassing all severities) develop inhibitory anti-factor VIII antibodies (inhibitors) following replacement therapy remain an enigma. Under physiological conditions, endogenous factor VIII is recognized by the immune system. Likewise, numerous observations indicate that, in hemophilia A patients without inhibitors, exogenous therapeutic factor VIII is immunologically assessed and tolerated...
December 4, 2018: Haematologica
Prina Mehta, Ali A Al-Kinani, Muhammad Sohail Arshad, Neenu Singh, Susanna M van der Merwe, Ming-Wei Chang, Raid G Alany, Zeeshan Ahmad
This manuscript reports on Electrohydrodynamic Atomisation (EHDA) to engineer on-demand novel coatings for ocular contact lenses. A formulation approach was adopted to modulate the release of timolol maleate (TM) using chitosan and borneol. Polymers polyvinylpyrrolidone (PVP) and poly (N-isopropylacrylamide) (PNIPAM) were utilised to encapsulate TM and were electrically atomised to produce optimised, stationary contact lens coatings. The particle and fibre diameter, thermal stability, material compatibility of the formed coatings; their in vitro release-modulating effect and ocular tolerability were investigated...
December 1, 2018: Journal of Pharmaceutical Sciences
Juliane Becher, Luca Simula, Elisabetta Volpe, Claudio Procaccini, Claudia La Rocca, Pasquale D'Acunzo, Valentina Cianfanelli, Flavie Strappazzon, Ignazio Caruana, Francesca Nazio, Gerrit Weber, Vincenzo Gigantino, Gerardo Botti, Fabiola Ciccosanti, Giovanna Borsellino, Silvia Campello, Georgia Mandolesi, Marco De Bardi, Gian Maria Fimia, Marcello D'Amelio, Francesca Ruffini, Roberto Furlan, Diego Centonze, Gianvito Martino, Paola Braghetta, Martina Chrisam, Paolo Bonaldo, Giuseppe Matarese, Franco Locatelli, Luca Battistini, Francesco Cecconi
Regulatory T cells (Treg ) are necessary to maintain immunological tolerance and are key players in the control of autoimmune disease susceptibility. Expression of the transcription factor FOXP3 is essential for differentiation of Treg cells and indispensable for their suppressive function. However, there is still a lack of knowledge about the mechanisms underlying its regulation. Here, we demonstrate that pro-autophagy protein AMBRA1 is also a key modulator of T cells, regulating the complex network that leads to human Treg differentiation and maintenance...
December 3, 2018: Developmental Cell
Martina Rudnicki, Ghoncheh Abdifarkosh, Emmanuel Nwadozi, Sofhia V Ramos, Armin Makki, Diane M Sepa-Kishi, Rolando B Ceddia, Christopher Gr Perry, Emilie Roudier, Tara L Haas
Impaired angiogenesis is a hallmark of metabolically dysfunctional adipose tissue in obesity. However, the underlying mechanisms restricting angiogenesis within this context remain ill-defined. Here, we demonstrate that induced endothelial-specific depletion of the transcription factor Forkhead Box O1 (FoxO1) in male mice led to increased vascular density in adipose tissue. Upon high-fat diet feeding, endothelial cell FoxO1-deficient mice exhibited even greater vascular remodeling in the visceral adipose depot, which was paralleled with a healthier adipose tissue expansion, higher glucose tolerance and lower fasting glycemia concomitant with enhanced lactate levels...
December 4, 2018: ELife
Kenji Goto
Acute urinary retention is rare symptom in young adolescent girls. Imperforate hymen can be a cause of acute urinary retention possibly due to the pressure effect of the distended vagina (hematocolpos) on the lower urinary tract. However, the mechanism of progression to urinary retention is unknown. We report on two cases of adolescent girls with imperforate hymen who presented with acute urinary retention. A series of volume tolerance tests of the urinary bladder and urodynamic studies before operation revealed highly elevated urethral resistance, which was induced by interaction of large amount of urinary volume in the bladder and the large size of hematocolpos...
December 3, 2018: Journal of Obstetrics and Gynaecology Research
François Singh, Joffrey Zoll, Urs Duthaler, Anne-Laure Charles, Miljenko V Panajatovic, Gilles Laverny, Thomas G McWilliams, Daniel Metzger, Bernard Geny, Stephan Krähenbühl, Jamal Bouitbir
Statins inhibit cholesterol biosynthesis and lower serum LDL-cholesterol levels. Statins are generally well tolerated, but can be associated with potentially life-threatening myopathy of unknown mechanism. We have shown previously that statins impair PGC-1β expression in human and rat skeletal muscle, suggesting that PGC-1β may play a role in statin-induced myopathy. PGC-1β is a transcriptional co-regulator controlling the expression of important genes in mitochondrial biogenesis, antioxidative capacity and energy metabolism...
December 3, 2018: Archives of Toxicology
Stella Maris Honoré, Maria Virginia Grande, Jorge Gomez Rojas, Sara Serafina Sánchez
Smallanthus sonchifolius (yacon), a native plant of South America, was observed to improve lipid profile in rodents and humans. This study aimed to investigate the antiobesity properties of yacon roots in a high-fat-diet (HFD) model and the underlying mechanisms. A total of 30 Wistar male rats were divided into five groups ( n =6): the standard chow diet (SD) group was fed a SD; the HFD group was fed a HFD; and the HFD Y340 and HFD Y680 groups were fed a HFD plus yacon flour (340 and 680 mg FOS/kg b. w./day, respectively)...
2018: Journal of Obesity
Katharina Bomans, Judith Schenz, Isabella Sztwiertnia, Dominik Schaack, Markus Alexander Weigand, Florian Uhle
Innate immune memory describes the functional reprogramming of innate immune cells after pathogen contact, leading to either a boosted (trained immunity) or a diminished (immune tolerance) response to a secondary stimulus. Immune tolerance or "sepsis-induced immunosuppression" is a typical hallmark of patients after sepsis survival, characterized by hypo-responsiveness of the host's immune system. This condition renders the host vulnerable for a persisting infection or the occurrence of secondary, often opportunistic infections, along with an increased mortality rate...
2018: Frontiers in Immunology
Patrick T LaBreck, Gregory K Rice, Adrian C Paskey, Emad M Elassal, Regina Z Cer, Natasha N Law, Carey D Schlett, Jason W Bennett, Eugene V Millar, Michael W Ellis, Theron Hamilton, Kimberly A Bishop-Lilly, D Scott Merrell
Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTI). Some S. aureus strains harbor plasmids that carry genes that affect resistance to biocides. Among these genes, qacA encodes the QacA Multidrug Efflux Pump that imparts decreased susceptibility to chlorhexidine, a biocide used ubiquitously in healthcare facilities. Furthermore, chlorhexidine has been considered as a S. aureus decolonization strategy in community settings. We previously conducted a chlorhexidine-based SSTI prevention trial among Ft...
2018: Frontiers in Microbiology
Wilson Mitsuo Tatagiba Kuwabara, Caroline Naomi Fukusawa Yokota, Rui Curi, Tatiana Carolina Alba-Loureiro
Obesity and diabetes implicate in various health complications and increased mortality caused by infection. Innate immune system is broadly affected by these diseases, leading the patients to an immunosuppressive state. A mechanism that leads innate immune cells to a less capacity of killing microorganism is the impaired TLR4 activation. TLR4 recognizes a component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS), and when activated increases the production of inflammatory substances...
December 3, 2018: Scientific Reports
Amanda N Samuels, Manuela Roggiani, Jun Zhu, Mark Goulian, Rahul M Kohli
Bacteria have a remarkable ability to survive, persist, and ultimately adapt to environmental challenges. A ubiquitous environmental hazard is DNA damage and most bacteria have evolved a network of genes known as the SOS response to combat genotoxic stress. The SOS response aids in bacterial survival by regulating genes involved in DNA repair and damage tolerance. Recently, the SOS response has been shown to play an important role in bacterial pathogenesis, yet the role of the SOS response in non-pathogenic organisms and in physiological settings remains underexplored...
December 3, 2018: Infection and Immunity
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