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Haruta Mogami, Shigeo Yura, Eiji Kondoh, Hiroshi Masutani, Junji Yodoi, Ikuo Konishi
AIM: Thioredoxin binding protein-2 (TBP-2), which is identical to thioredoxin interacting protein (Txnip), controls cellular proliferation and differentiation. The aim of the present study was to compare TBP-2 protein and mRNA expression in human placenta during the three trimesters of pregnancy and to investigate the role of hypoxia in the change of these expressions in placental tissue. A secondary objective was to determine the gene expression of peroxisome proliferator-activated receptors (PPARs) in TBP-2 deficient placenta using TBP-2 gene disrupted mice (TBP-2(-/-) )...
October 20, 2016: Journal of Obstetrics and Gynaecology Research
Liming Yu, Chongxi Fan, Zhi Li, Jian Zhang, Xiaodong Xue, Yinli Xu, Guolong Zhao, Yang Yang, Huishan Wang
Stress hyperglycemia is commonly observed in patients suffering from ischemic heart disease. It not only worsens cardiovascular prognosis but also attenuates the efficacies of various cardioprotective agents. This study aimed to investigate the protective effect of melatonin against myocardial ischemia-reperfusion (MI/R) injury in acute hyperglycemic state with a focus on Notch1/Hes1/Akt signaling and intracellular thioredoxin (Trx) system. Sprague-Dawley rats were subjected to MI/R surgery and high glucose (HG, 500 g/L) infusion (4 ml/kg/h) to induce temporary hyperglycemia...
October 18, 2016: Journal of Pineal Research
Weijie Chen, Junlian Wang, Yong Luo, Tao Wang, Xiaochun Li, Aiyun Li, Jia Li, Kang Liu, Baolin Liu
BACKGROUND: This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue. METHODS: To induce ER stress, epididymal adipose tissue from mice or differentiated 3T3 adipocytes were exposed to high glucose. The effects of Rb1 and CK on reactive oxygen species production, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation, insulin signaling activation, and glucose uptake were detected by western blot, emzyme-linked immunosorbent assay, or fluorometry...
October 2016: Journal of Ginseng Research
M B Huante, S Gupta, V C Calderon, S J Koo, M Sinha, B A Luxon, N J Garg, J J Endsley
Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli...
September 28, 2016: Tuberculosis
Hisa Hui Ling Tseng, Chi Teng Vong, Yiu Wa Kwan, Simon Ming-Yuen Lee, Maggie Pui Man Hoi
Excessive production of reactive oxygen species (ROS) induced by hyperglycemia increased the secretion of interleukin-1β (IL-1β), which contributes to the pathogenesis of diabetes and its complications. Although high glucose (HG)-induced oxidative stress and aberrant Ca(2+) channels activity causes an increase in transmembrane Ca(2+) influx, however the relative contribution of Transient receptor potential (TRP) channels is not well studied. Here, we identified that HG (30 mM glucose for 48 h) induced the activation of the NLRP3-ASC inflammasome, leading to caspase-1 activation, and IL-1β and IL-18 secretion in human monocytic cell lines...
October 12, 2016: Scientific Reports
James R Dotimas, Austin W Lee, Angela B Schmider, Shannon H Carroll, Anu Shah, Julide Bilen, Kayla R Elliott, Ronald B Myers, Roy J Soberman, Jun Yoshioka, Richard T Lee
Metabolic studies suggest that the absorptive capacity of the small intestine for fructose is limited, though the molecular mechanisms controlling this process remain unknown. Here we demonstrate that thioredoxin-interacting protein (Txnip), which regulates glucose homeostasis in mammals, binds to fructose transporters and promotes fructose absorption by the small intestine. Deletion of Txnip in mice reduced fructose transport into the peripheral bloodstream and liver, as well as the severity of adverse metabolic outcomes resulting from long-term fructose consumption...
October 11, 2016: ELife
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
Linnéa Schmidt, Sathishkumar Baskaran, Patrik Johansson, Narendra Padhan, Damian Matuszewski, Lydia C Green, Ludmila Elfineh, Shimei Wee, Maria Häggblad, Ulf Martens, Bengt Westermark, Karin Forsberg-Nilsson, Lene Uhrbom, Lena Claesson-Welsh, Michael Andäng, Ida-Maria Sintorn, Bo Lundgren, Ingrid Lönnstedt, Cecilia Krona, Sven Nelander
Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures...
September 28, 2016: Oncotarget
Lei Jiang, Lei Zhang, Kai Kang, Dongsheng Fei, Rui Gong, Yanhui Cao, Shangha Pan, Mingran Zhao, Mingyan Zhao
NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI...
September 16, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
S Sayols-Baixeras, I Subirana, C Lluis-Ganella, F Civeira, J Roquer, A N Do, D Absher, D Muñoz, C Soriano-Tárraga, J Jiménez-Conde, J Ordovas, M Senti, S Aslibekyan, J Marrugat, D K Arnett, R Elosua
Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n=645) and validation in the Framingham Offspring Study (n=2,542)...
September 15, 2016: Human Molecular Genetics
Alexandra M Hetherington, Cynthia G Sawyez, Emma Zilberman, Alexandra M Stoianov, Debra L Robson, Nica M Borradaile
BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved...
2016: Cellular Physiology and Biochemistry
Guosheng Cao, Nan Jiang, Yang Hu, Yuanyuan Zhang, Guangyun Wang, Mingzhu Yin, Xiaonan Ma, Kecheng Zhou, Jin Qi, Boyang Yu, Junping Kou
Ruscogenin, an important steroid sapogenin derived from Ophiopogon japonicus, has been shown to inhibit cerebral ischemic injury. However, its potential molecular action on blood-brain barrier (BBB) dysfunction after stroke remains unclear. This study aimed to investigate the effects of ruscogenin on BBB dysfunction and the underlying mechanisms in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-injured mouse brain microvascular endothelial cells (bEnd...
2016: International Journal of Molecular Sciences
Terri D McBride, U Andrew, Nicko Ly, Julio G Soto
RNA sequencing of untreated and r-Moj-DM treated SK-Mel-28 cells was performed after 6 h, to begin unraveling the apoptotic pathway induced by r-Moj-DM. Bioinformatic analyses of RNA sequencing data yielded 40 genes that were differentially expressed. Nine genes were upregulated and 31 were downregulated. qRT-PCR was used to validate differential expression of 13 genes with known survival or apoptotic-inducing activities. Expression of BNiP3, IGFBP3, PTPSF, Prune 2, TGF-ß, and TXNIP were compared from cells treated with r-Moj-DN (a strong apoptotic inducer) or r-Moj-DA (a non-apoptotic inducer) for 1 h, 2 h, 4 h, and 6 h after treatment...
October 2016: Toxicon: Official Journal of the International Society on Toxinology
Ren-Hong Du, Fang-Fang Wu, Ming Lu, Xiao-Dong Shu, Jian-Hua Ding, Guangyu Wu, Gang Hu
Mitochondrial uncoupling protein 2 (UCP2) has been well characterized to control the production of reactive oxygen species (ROS) and astrocytes are the major cells responsible for the ROS production and the inflammatory responses in the brain. However, the function of UCP2 in astrocytes and the contribution of astrocytic UCP2 to depression remain undefined. Herein, we demonstrated that UCP2 knockout (KO) mice displayed aggravated depressive-like behaviors, impaired neurogenesis, and enhanced loss of astrocytes in the chronic mild stress (CMS)-induced anhedonia model of depression...
August 18, 2016: Redox Biology
Juha J Hulmi, Jaakko Hentilä, Keith C DeRuisseau, Bernardo M Oliveira, Konstantinos G Papaioannou, Reija Autio, Urho M Kujala, Olli Ritvos, Heikki Kainulainen, Ayhan Korkmaz, Mustafa Atalay
Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking...
August 20, 2016: Free Radical Biology & Medicine
Milankumar V Prajapati, Olujoba O Adebolu, Benjamin M Morrow, Joseph M Cerreta
Extensive industrial and military uses of tungsten have raised the possibilities of human occupational and environmental exposure to nanoparticles of this metal, with concomitant health concerns. The goal of this study was to investigate the potential mechanism of pulmonary toxicity associated with inhaled tungsten (IV) oxide nanoparticles (WO3 NPs) in Golden Syrian Hamsters. Animals exposed to WO3 NPs via inhalation were divided into three groups - control and two treatment groups exposed to either 5 or 10 mg/m(3) of aerosolized WO3 NPs for 4 h/day for four days...
August 17, 2016: Experimental Biology and Medicine
Gemma Pujadas, Valeria De Nigris, Francesco Prattichizzo, Lucia La Sala, Roberto Testa, Antonio Ceriello
Dipeptidyl peptidase-4 inhibitors are widely used in type 2 diabetes. Endothelium plays a crucial role maintaining vascular integrity and function. Chronic exposure to high glucose drives to endothelial dysfunction generating oxidative stress. Teneligliptin is a novel dipeptidyl peptidase-4 inhibitor with antioxidant properties. This study is aimed to verify a potential protective action of teneligliptin in endothelial cells exposed to high glucose. Human umbilical vein endothelial cells were cultured under normal (5 mmol/L) or high glucose (25 mmol/L) during 21 days, or at high glucose during 14 days followed by 7 days at normal glucose, to reproduce the high-metabolic memory state...
August 16, 2016: Endocrine
Ming Wang, Jing Zhao, Nan Zhang, Jianghua Chen
Astilbin is a flavonoid compound derived from the rhizome of Smilax china L. The effects and possible molecular mechanisms of astilbin on potassium oxonate-induced hyperuricemia mice were investigated in this study. Different dosages of astilbin (5, 10, and 20mg/kg) were administered to induce hyperuricemic mice. The results demonstrated that the serum uric acid (Sur) level was significantly decreased by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) with astilbin, related with suppressing role in meditation of Glucose transporter 9 (GLUT9), Human urate transporter 1 (URAT1) expression and up-regulation of ABCG2, Organic anion transporter 1/3 (OAT1/3) and Organic cation transporter 1 (OCT1)...
August 11, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Michelle L Baack, Benjamin J Forred, Tricia D Larsen, Danielle N Jensen, Angela L Wachal, Muhammad Ali Khan, Peter F Vitiello
RATIONALE: Infants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development...
2016: PloS One
Yousong Su, Wenhua Ding, Mengjuan Xing, Dake Qi, Zezhi Li, Donghong Cui
Although previous studies showed the reduced risk of cancer in patients with schizophrenia, whether patients with schizophrenia possess genetic factors that also contribute to tumor suppressor is still unknown. In the present study, based on our previous microarray data, we focused on the tumor suppressor genes TXNIP and AF1q, which differentially expressed in patients with schizophrenia. A total of 413 patients and 578 healthy controls were recruited. We found no significant differences in genotype, allele, or haplotype frequencies at the selected five single nucleotide polymorphisms (SNPs) (rs2236566 and rs7211 in TXNIP gene; rs10749659, rs2140709, and rs3738481 in AF1q gene) between patients with schizophrenia and controls...
August 10, 2016: Molecular Neurobiology
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