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https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#1
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28815513/an-update-on-p2y13-receptor-signalling-and-function
#2
Raquel Pérez-Sen, Rosa Gómez-Villafuertes, Felipe Ortega, Javier Gualix, Esmerilda G Delicado, María Teresa Miras-Portugal
The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y13 is one of the latest P2Y receptors identified, a novel member of the Gi-coupled P2Y receptor subfamily that responds to ADP, together with P2Y12 and P2Y14. Pharmacological studies drew attention to this new ADP receptor, with a pharmacology that overlaps that of P2Y12 receptors but with unique features and roles. The P2RY12-14 genes all reside on human chromosome 3 at 3q25...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28812766/modulatory-effects-of-arginine-glutamine-and-branched-chain-amino-acids-on-heat-shock-proteins-immunity-and-antioxidant-response-in-exercised-rats
#3
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Heat shock proteins (HSPs) are endogenous proteins whose function is to maintain the cell's tolerance to insult, and glutamine supplementation is known to increase HSP expression during intense exercise. Since few studies have addressed the possibility that supplementation with other amino acids could have similar effects to that of glutamine, our objective was to evaluate the effects of leucine, valine, isoleucine and arginine as potential stimulators of HSPs 25, 60, 70 and 90 in rats subjected to acute exercise as a stressing factor...
August 16, 2017: Food & Function
https://www.readbyqxmd.com/read/28810562/anti-depressant-like-effects-of-jieyu-chufan-capsules-in-a-mouse-model-of-unpredictable-chronic-mild-stress
#4
Hui Zhao, Bingyu Liang, Linjie Yu, Yun Xu
Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810189/hydroxy-substituted-trans-cinnamoyl-derivatives-as-multifunctional-tools-in-the-context-of-alzheimer-s-disease
#5
Angela De Simone, Manuela Bartolini, Andrea Baschieri, Kim Y P Apperley, Huan Huan Chen, Melissa Guardigni, Serena Montanari, Tereza Kobrlova, Ondrej Soukup, Luca Valgimigli, Vincenza Andrisano, Jeffrey W Keillor, Manuela Basso, Andrea Milelli
Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28810187/histochemical-and-immunohistochemical-examination-of-odontoblasts-petroblasts-in-petrodentine-formation-of-lungfish
#6
Shunya Oka, Ichiro Sasagawa, Mikio Ishiyama
OBJECTIVE: Petrodentine, the core of the lungfish tooth plate, is a well-mineralized tissue similar to mammalian enamel and analogous to enameloid in fish teeth. Petrodentine is formed solely by petroblasts, which are specialized odontoblasts, whereas enameloid is a composite tissue produced by both odontoblasts and dental epithelial cells. To clarify the details of petrodentine formation, petroblasts were investigated using histochemical and immunohistochemical techniques. METHODS: Extant lungfish (Lepidosiren paradoxa) were used in this study...
August 3, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28808322/neuroinflammation-alters-cellular-proteostasis-by-producing-endoplasmic-reticulum-stress-autophagy-activation-and-disrupting-erad-activation
#7
Cristina Pintado, Sandra Macías, Helena Domínguez-Martín, Angélica Castaño, Diego Ruano
Proteostasis alteration and neuroinflammation are typical features of normal aging. We have previously shown that neuroinflammation alters cellular proteostasis through immunoproteasome induction, leading to a transient decrease of proteasome activity. Here, we further investigated the role of acute lipopolysaccharide (LPS)-induced hippocampal neuroinflammation in cellular proteostasis. In particular, we focused on macroautophagy (hereinafter called autophagy) and endoplasmic reticulum-associated protein degradation (ERAD)...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#8
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807675/substantial-protection-against-mptp-associated-parkinson-s-neurotoxicity-in-vitro-and-in-vivo-by-anti-cancer-agent-su4312-via-activation-of-mef2d-and-inhibition-of-mao-b
#9
Baojian Guo, Shengquan Hu, Chengyou Zheng, Hongyu Wang, Fangcheng Luo, Haitao Li, Wei Cui, Xifei Yang, Guozhen Cui, Shinghung Mak, Tony Chung-Lit Choi, Edmond Dik-Lung Ma, Yuqiang Wang, Simon Ming Yuen Lee, Zaijun Zhang, Yifan Han
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807341/ultrastructural-examination-of-skin-biopsies-may-assist-in-diagnosing-mitochondrial-cytopathy-when-muscle-biopsies-yield-negative-results
#10
John L McAfee, Christine B Warren, Richard A Prayson
Ultrastructural evaluation of skin biopsies has been utilized for diagnosis of mitochondrial disease. This study investigates how frequently skin biopsies reveal mitochondrial abnormalities, correlates skin and muscle biopsy findings, and describes clinical diagnoses rendered following the evaluation. A retrospective review of surgical pathology reports from 1990 to 2015 identified skin biopsies examined by electron microscopy for suspected metabolic disease. A total of 630 biopsies were included from 615 patients...
August 2017: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/28807209/induction-of-autophagy-reduces-ischemia-reperfusion-injury-in-steatotic-rat-livers
#11
Chunyi Kan, Anding Liu, Haoshu Fang, Olaf Dirsch, Uta Dahmen, Michael Boettcher
BACKGROUND: Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the reasons is an underlying impairment of autophagy. Autophagy is regulated by glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinases (ERK1/2) pathways. Both of them are target proteins of a cell-protective drug, lithium chloride. Lithium chloride treatment reduces IRI in many organs including liver. Therefore, we aimed to investigate the effect of lithium chloride treatment on autophagy induction in steatotic rat livers...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28806275/effects-of-creatine-and-carbohydrate-loading-on-cycling-time-trial-performance
#12
Kristyen A Tomcik, Donny M Camera, Julia L Bone, Megan L Ross, Nikki A Jeacocke, Bill Tachtsis, Joan Senden, Luc J C van Loon, John A Hawley, Louise M Burke
INTRODUCTION: Creatine- and carbohydrate-loading are dietary strategies used to enhance exercise capacity. This study examined the metabolic and performance effects of a combined creatine and CHO-loading regiment on time-trial (TT) cycling bouts. METHODS: Eighteen well-trained (~65mL[BULLET OPERATOR]kg[BULLET OPERATOR]min VO2peak) males completed three performance trials (PT) comprised of a 120-km cycling TT interspersed with alternating 1- and 4-km sprints (6 sprints each) performed every 10-km followed by an inclined ride to fatigue (~90% VO2peak)...
August 11, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28805660/prolyl-hydroxylase-2-inactivation-enhances-glycogen-storage-and-promotes-excessive-neutrophilic-responses
#13
Pranvera Sadiku, Joseph A Willson, Rebecca S Dickinson, Fiona Murphy, Alison J Harris, Amy Lewis, David Sammut, Ananda S Mirchandani, Eilise Ryan, Emily R Watts, A A Roger Thompson, Helen M Marriott, David H Dockrell, Cormac T Taylor, Martin Schneider, Patrick H Maxwell, Edwin R Chilvers, Massimilliano Mazzone, Veronica Moral, Chris W Pugh, Peter J Ratcliffe, Christopher J Schofield, Bart Ghesquiere, Peter Carmeliet, Moira Kb Whyte, Sarah R Walmsley
Fully activated innate immune cells are required for effective responses to infection, but their prompt deactivation and removal are essential for limiting tissue damage. Here, we have identified a critical role for the prolyl hydroxylase enzyme Phd2 in maintaining the balance between appropriate, predominantly neutrophil-mediated pathogen clearance and resolution of the innate immune response. We demonstrate that myeloid-specific loss of Phd2 resulted in an exaggerated inflammatory response to Streptococcus pneumonia, with increases in neutrophil motility, functional capacity, and survival...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28804986/effects-of-hydroxycitric-acid-on-lipid-droplet-accumulation-in-chicken-embryos
#14
Mengling Peng, Longlong Li, Lei Yu, Chongyang Ge, Haitian Ma
This study was conducted to determine the impact of (-)-hydroxycitric acid ((-)-HCA) on biochemical indices and lipid metabolism parameters in chicken embryos. Two hundred and forty fertilized eggs were divided into six groups and injected with (-)-HCA at concentrations of 0, 0.1, 0.5, 1.0, 10.0 and 50 mg/kg (n = 40). After 19 days of incubation, serum and liver were collected for analysis of biochemical indices and lipid metabolism parameters. Results showed no significant differences on serum biochemical indices: 1-50 mg/kg (-)-HCA significantly increased serum glucose and hepatic glycogen contents (P < 0...
August 14, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/28803855/elucidating-the-functions-of-brain-gsk3%C3%AE-possible-synergy-with-gsk3%C3%AE-upregulation-and-reversal-by-antidepressant-treatment-in-a-mouse-model-of-depressive-like-behaviour
#15
Dmitri Pavlov, Nataliia Markova, Lucien Bettendorff, Vladimir Chekhonin, Igor Pomytkin, Viktoria Lioudyno, Andrei Svistunov, Eugene Ponomarev, Klaus-Peter Lesch, Tatyana Strekalova
Glycogen synthase kinase 3 (GSK3) has been linked to the mechanisms of stress, mood regulation, and the effects of antidepressants. The functions of the GSK3β isoform have been extensively investigated, but little is known about the α-isoform, although they may functionally related. In a recently established modified swim test with a third delayed swim exposure, brain GSK3β mRNA expression positively correlated with floating behavior on the third test. A two-week-long pretreatment regime with imipramine (7...
August 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28803129/low-plasma-glucose-limits-glucose-metabolism-by-rbcs-and-heart-in-some-species-of-teleosts
#16
William R Driedzic
Within teleosts there is a species range in plasma glucose levels from undetectable to 20mM. At low plasma glucose levels the gradient from the extracellular to the intracellular space is decreased. The impact of this on glucose metabolism by RBCs and heart from species with different steady state levels of plasma glucose (Atlantic cod ~5mM; Atlantic salmon ~5mM, cunner ~1mM, lumpfish <1mM; short-horned sculpin <1mM) is the subject of this review. Under normoxia, at physiological levels of extracellular glucose, RBCs and heart produce lactate although the contribution of anaerobic metabolism to ATP production is small...
August 9, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28803110/dynamics-of-microbial-activities-and-community-structures-in-activated-sludge-under-aerobic-starvation
#17
Wenlong Liu, Yongzhen Peng, Bin Ma, Linna Ma, Fangxu Jia, Xiyao Li
The knowledge of the effect of aerobic starvation on the functional bacterial activities and community structures is important for the recovery of nutrient removal in activated sludge system. Four aerobic starvation processes (3, 7, 14 and 30days) for nitrifiers and polyphosphate accumulating organisms (PAOs) were studied. The results showed that nitrifiers could utilize the released ammonium for growth during the first 7days of the aerobic starvation, and then gradually decayed. In the recovery period, the slower recovery ability of nitrite-oxidizing bacteria (NOB) than ammonium-oxidizing bacteria (AOB) contributed to the nitrite accumulation...
July 25, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28802581/pkm2-aggravates-palmitate-induced-insulin-resistance-in-hepg2-cells-via-stat3-pathway
#18
Ling Chen, Zhuqi Tang, Xiaohua Wang, Hong Ma, Dandan Shan, Shiwei Cui
Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β)...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28801776/effects-of-training-status-on-pdh-regulation-in-human-skeletal-muscle-during-exercise
#19
Anders Gudiksen, Lærke Bertholdt, Tomasz Stankiewicz, Jonas Tybirk, Peter Plomgaard, Jens Bangsbo, Henriette Pilegaard
Pyruvate dehydrogenase (PDH) is the gateway enzyme for carbohydrate-derived pyruvate feeding into the TCA cycle. PDH may play a central role in regulating substrate shifts during exercise, but the influence of training state on PDH regulation during exercise is not fully elucidated. The purpose of this study was to investigate the impact of training state on post-translational regulation of PDHa activity during submaximal and exhaustive exercise. Eight untrained and nine endurance exercise-trained healthy male subjects performed incremental exercise on a cycle ergometer: 40 min at 50% incremental peak power output (IPPO), 10 min at 65% (IPPO), followed by 80% (IPPO) until exhaustion...
August 11, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28800070/pathogenesis-of-lafora-disease-transition-of-soluble-glycogen-to-insoluble-polyglucosan
#20
REVIEW
Mitchell A Sullivan, Silvia Nitschke, Martin Steup, Berge A Minassian, Felix Nitschke
Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes EPM2A (laforin) or EPM2B (malin). It characteristically involves the accumulation of insoluble glycogen-derived particles, named Lafora bodies (LBs), which are considered neurotoxic and causative of the disease. The pathogenesis of LD is therefore centred on the question of how insoluble LBs emerge from soluble glycogen...
August 11, 2017: International Journal of Molecular Sciences
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