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https://www.readbyqxmd.com/read/28636232/a-genetic-stochastic-process-model-for-genome-wide-joint-analysis-of-biomarker-dynamics-and-disease-susceptibility-with-longitudinal-data
#1
Liang He, Ilya Zhbannikov, Konstantin G Arbeev, Anatoliy I Yashin, Alexander M Kulminski
Unraveling the underlying biological mechanisms or pathways behind the effects of genetic variations on complex diseases remains one of the major challenges in the post-GWAS (where GWAS is genome-wide association study) era. To further explore the relationship between genetic variations, biomarkers, and diseases for elucidating underlying pathological mechanism, a huge effort has been placed on examining pleiotropic and gene-environmental interaction effects. We propose a novel genetic stochastic process model (GSPM) that can be applied to GWAS and jointly investigate the genetic effects on longitudinally measured biomarkers and risks of diseases...
June 21, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28634786/inhibition-of-nf-%C3%AE%C2%BAb-activity-by-aminoguanidine-alleviates-neuroinflammation-induced-by-hyperglycemia
#2
Yuanjian Song, Fang Zhang, Changjiang Ying, Kiran Ashok Kumar, Xiaoyan Zhou
Neuroinflammation is a key feature of cerebral complication which is associated with diabetes mellitus (DM). Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of neuroinflammation. However, how iNOS facilitates the development of inflammation in brain is still unidentified. The aim of the present study was to investigate the association of iNOS and neuroinflammation in diabetic mice, and elucidate the potential mechanisms underlying aminoguanidine (AG), the selective inhibitor of iNOS, protected neurons against inflammation in diabetic mice...
June 20, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28634592/euglycemic-diabetic-ketoacidosis-with-prolonged-glucosuria-associated-with-the-sodium-glucose-cotransporter-2-canagliflozin
#3
Daniel A Kelmenson, Kelsey Burr, Yusra Azhar, Paul Reynolds, Chelsea A Baker, Neda Rasouli
Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control by a reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. This unique mechanism, independent of insulin secretion and beta cell function, has made this class of medication desirable in patients with type 2 diabetes. However in May 2015, the US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors...
April 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28633346/tetramethylpyrazine-reverses-intracerebroventricular-streptozotocin-induced-memory-deficits-by-inhibiting-gsk-3%C3%AE
#4
Fen Lu, Xu Li, Wei Li, Ke Wei, Yong Yao, Qianlin Zhang, Xinliang Liang, Jiewen Zhang
Brain dysfunction, especially cognitive impairment, is one of the main complications in Alzheimer's disease (AD), which threatens the health of 46.8 million people worldwide. At present, the pathogenesis of cognitive dysfunction is only partially understood, and effective therapies for memory loss in AD remain elusive. Tetramethylpyrazine (TMP) is one of the major bioactive compounds purified from Chuanxiong, a Chinese herb used for the treatment of neurovascular and cardiovascular diseases. The neuroprotective properties of TMP are evident in some neurodegenerative diseases, including Parkinson's disease...
June 15, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28631505/methylglyoxal-derived-hydroimidazolone-1-evokes-inflammatory-reactions-in-endothelial-cells-via-an-interaction-with-receptor-for-advanced-glycation-end-products
#5
Yuji Ishibashi, Takanori Matsui, Nobutaka Nakamura, Ami Sotokawauchi, Yuichiro Higashimoto, Sho-Ichi Yamagishi
OBJECTIVE: Glyceraldehyde-derived advanced glycation end products contribute to vascular inflammation in diabetes. However, what advanced glycation end product structure could evoke inflammatory reactions remains unknown. We examined whether and how methylglyoxal-derived hydroimidazolone 1, one of the advanced glycation end products formed from glyceraldehyde, elicits inflammatory reactions in human umbilical vein endothelial cells. MATERIALS AND METHODS: Glyceraldehyde-advanced glycation end products-aptamer was prepared using a systemic evolution of ligands by exponential enrichment...
June 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28631352/overexpressing-stamp2-attenuates-adipose-tissue-angiogenesis-and-insulin-resistance-in-diabetic-apoe-ldlr-mouse-via-a-ppar%C3%AE-cd36-pathway
#6
Feng Wang, Lu Han, Ran-Ran Qin, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Meng-Xiong Tang, Yun Zhang, Ming Zhong, Wei Zhang
The aim of this study was to investigate whether overexpression of STAMP2 improves insulin resistance by regulating angiogenesis in adipose tissues. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Histological and morphological analysis demonstrated that STAMP2 gene overexpression reduced adipocyte size, angiogenesis in epididymal and brown adipose tissues. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited after STAMP2 gene overexpression...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28630633/djc-suppresses-advanced-glycation-end-products-induced-jak-stat-signaling-and-ros-in-mesangial-cells
#7
Min Sun, Yan Li, Wenjie Bu, Jindong Zhao, Jianliang Zhu, Lingling Gu, Pingping Zhang, Zhaohui Fang
The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28627674/mir-200c-serves-an-important-role-in-h5v-endothelial-cells-in-high-glucose-by-targeting-notch1
#8
Yunfeng Zhang, Qiang Guan, Xing Jin
Diabetic vasculopathy is the leading cause of impairment and death in diabetic patients, a variety of factors are involved in its underlying pathological process, however, endothelial cell (EC) dysfunction serves a significant role in the process. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates, due to their ability to regulate multiple targets involved in ECs. The aim of the present study was to investigate the role of miR‑200c in regulating ECs in high glucose condition. To investigate the role of miR‑200c in regulating hyperglycemia induced ECs by targeting Notch1, ECs H5V cells were cultured in high sugar conditions to initiate the inhibition of Notch1, the same cells in normal medium as the control...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627440/microrna-21-regulates-hepatic-glucose-metabolism-by-targeting-foxo1
#9
Ailing Luo, Haibo Yan, Jichao Liang, Chunyuan Du, Xuemei Zhao, Lijuan Sun, Yong Chen
Abnormal activation of hepatic gluconeogenesis is a major contributor to fasting hyperglycemia in type 2 diabetes; however, the potential role of microRNAs in gluconeogenesis remains unclear. Here, we showed that hepatic expression levels of microRNA-21 (miR-21) were decreased in db/db and high-fat diet (HFD)-induced diabetic mice. Adenovirus-mediated overexpression of miR-21 decreased the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and inhibited glucose production in primary mouse hepatocytes...
June 13, 2017: Gene
https://www.readbyqxmd.com/read/28626770/upregulation-of-tumor-necrosis-factor-%C3%AE-induced-protein-8-like-2-mrna-is-negatively-correlated-with-serum-concentrations-of-tumor-necrosis-factor-%C3%AE-and-interleukin-6-in-type-2-diabetes-mellitus
#10
Yongliang Liu, Xinmei Wang, Yan Zhao, Peiqing Zhao, Lianqing Wang, Qiaoli Zhai, Xiaowei Zhang, Wenxiu Tian, Xinxin Xiang, Tao Li
BACKGROUND: Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a negative regulator of natural and adaptive immunity. The role of TIPE2 in type 2 diabetes mellitus (T2DM) remains unknown, although TIPE2 plays key roles in preserving inflammatory homeostasis. METHODS: TIPE2 expression was measured by Western blotting and real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs) isolated from T2DM patients and healthy controls, and tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and other related biometabolic parameters were detected using a nephelometer or by ELISA...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28624657/adiponectin-improves-the-osteointegration-of-titanium-implant-under-diabetic-conditions-by-reversing-mitochondrial-dysfunction-via-the-ampk-pathway-in-vivo-and-in-vitro
#11
Xiao-Fan Hu, Lin Wang, Yi-Zhao Lu, Geng Xiang, Zi-Xiang Wu, Ya-Bo Yan, Yang Zhang, Xiong Zhao, Yuan Zang, Lei Shi, Wei Lei, Ya-Fei Feng
Diabetes-induced reactive oxygen species (ROS) overproduction would result in compromised osteointegration of titanium implant (TI) and high rate of implant failure, yet the underlying mechanisms remain elusive. Adiponectin (APN) is a fat-derived adipocytokine with strong antioxidant, mitochondrial-protective and anti-diabetic efficacies. We hypothesized that mitochondrial dysfunction under diabetes may account for the oxidative stress in osteoblasts and titanium-bone interface (TBI) instability, which could be ameliorated by APN...
June 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28623929/the-potential-regulatory-mechanisms-of-the-gonadotropin-releasing-hormone-in-gonadotropin-transcriptions-identified-with-bioinformatics-analyses
#12
Wei Xiang, Baoyun Zhang, Fenglin Lv, Guangde Feng, Long Chen, Fang Yang, Ke Zhang, Chunyu Cao, Pingqing Wang, Mingxing Chu
BACKGROUND: The regulation of gonadotropin synthesis and release by gonadotropin-releasing hormone (GnRH) plays an essential role in the neuroendocrine control of reproduction. However, the mechanisms underlying gonadotropin regulation by GnRH pulse frequency and amplitude are still ambiguous. This study aimed to explore the molecular mechanisms and biological pathways associated with gonadotropin synthesis by GnRH pulse frequencies and amplitudes. METHODS: Using GSE63251 datasets downloaded from the Gene Expression Omnibus (GEO), differentially expressed genes (DEGs) were screened by comparing the RNA expression from the GnRH pulse group, the GnRH tonic group and the control group...
June 17, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28621051/plasma-microrna-16-5p-17-5p-and-20a-5p-novel-diagnostic-biomarkers-for-gestational-diabetes-mellitus
#13
Ya-Lei Cao, Yan-Ju Jia, Bao-Heng Xing, Dan-Dan Shi, Xiu-Juan Dong
AIM: To explore whether plasma microRNA-16-5p, -17-5p and -20a-5p can be used as diagnostic biomarkers in gestational diabetes mellitus (GDM) and to investigate the relationship between those microRNAs and the risk factors of GDM (body mass index [BMI], insulin resistance [IR] and tumor necrosis factor-α (TNF-α)). METHODS: A total of 85 pregnant women with GDM and 72 pregnant women without GDM were enrolled in this study. The plasma concentration of microRNAs (microRNA-16-5p, -17-5p, -19a-3p, -19b-3p, -20a-5p) was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR)...
June 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28620823/the-vegf-a-inhibitor-sflt-1-improves-renal-function-by-reducing-endothelial-activation-and-inflammation-in-a-mouse-model-of-type-1-diabetes
#14
Pascal Bus, Marion Scharpfenecker, Priscilla Van Der Wilk, Ron Wolterbeek, Jan A Bruijn, Hans J Baelde
AIMS/HYPOTHESIS: Animal models of diabetic nephropathy show increased levels of glomerular vascular endothelial growth factor (VEGF)-A, and several studies have shown that inhibiting VEGF-A in animal models of diabetes can prevent albuminuria and glomerular hypertrophy. However, in those studies, treatment was initiated before the onset of kidney damage. Therefore, the aim of this study was to investigate whether transfecting mice with the VEGF-A inhibitor sFlt-1 (encoding soluble fms-related tyrosine kinase 1) can reverse pre-existing kidney damage in a mouse model of type 1 diabetes...
June 15, 2017: Diabetologia
https://www.readbyqxmd.com/read/28618859/sitagliptin-attenuates-endothelial-dysfunction-of-zucker-diabetic-fatty-rats
#15
Huanyuan Wang, Yi Zhou, Zhiying Guo, Yu Dong, Jiahui Xu, Haixia Huang, Huirong Liu, Wen Wang
Although the contributions of sitagliptin to endothelial function in diabetes mellitus were previously reported, the potential mechanisms still remain undefined. Our research was intended to explore the underlying mechanisms of protective effects of sitagliptin treatment on endothelial dysfunction in Zucker diabetic fatty (ZDF) rats. Male lean nondiabetic Zucker rats were used as control and male obese ZDF rats were randomly divided into ZDF and ZDF + sitagliptin groups. The significant decrease in endothelium-dependent relaxation induced by acetylcholine was observed in mesenteric arteries and thoracic aorta rings of ZDF rats...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28618324/stem-cells-an-emerging-novel-therapeutic-for-type-1-diabetes-mellitus
#16
Umang G Thakkar, Aruna V Vanikar, Hargovind L Trivedi
Stem cell based strategies are therapeutically potent for treating type-1 diabetes mellitus owing to their intrinsic regenerative capacity and immunomodulatory properties to arrest autoimmune β-cell destruction, preserve residual β-cell mass, facilitate endogenous regeneration, ameliorate innate/ alloimmune graft rejection, restore β-cell-specific unresponsiveness in absence of chronic immunosuppression and to reverse hyperglycemia.
April 19, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28616250/potential-role-of-serum-and-urinary-biomarkers-in-diagnosis-and-prognosis-of-diabetic-nephropathy
#17
REVIEW
Carole G Campion, Oraly Sanchez-Ferras, Sri N Batchu
PURPOSE OF REVIEW: Diabetic nephropathy (DN) is a progressive kidney disease caused by alterations in kidney architecture and function, and constitutes one of the leading causes of end-stage renal disease (ESRD). The purpose of this review is to summarize the state of the art of the DN-biomarker field with a focus on the new strategies that enhance the sensitivity of biomarkers to predict patients who will develop DN or are at risk of progressing to ESRD. OBJECTIVE: In this review, we provide a description of the pathophysiology of DN and propose a panel of novel putative biomarkers associated with DN pathophysiology that have been increasingly investigated for diagnosis, to predict disease progression or to provide efficient personal treatment...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28615356/sulforaphane-reduces-hepatic-glucose-production-and-improves-glucose-control-in-patients-with-type-2-diabetes
#18
Annika S Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan M J Derry, Claes B Wollheim, Nils Wierup, Morey W Haymond, Stephen H Friend, Hindrik Mulder, Anders H Rosengren
A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature...
June 14, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28615247/lithium-induced-ndi-acetazolamide-reduces-polyuria-but-does-not-improve-urine-concentrating-ability
#19
Theun de Groot, Joan Doornebal, Birgitte M Christensen, Simone C Cockx, Anne P Sinke, Ruben Baumgarten, Jennifer J Bedford, Robert J Walker, Jack F Wetzels, Peter M T Deen
Lithium is the mainstay treatment for patients with bipolar disorder, but generally causes nephrogenic diabetes insipidus (NDI), a disorder in which the renal urine concentrating ability has become vasopressin-insensitive. Li-NDI is caused by lithium uptake by collecting duct principal cells and downregulation of AQP2 water channels, which are essential for water uptake from pro-urine. Recently, we found that the prophylactic administration of acetazolamide to mice effectively attenuated Li-NDI. To evaluate whether acetazolamide might benefit lithium-treated patients, we administered acetazolamide to mice with established Li-NDI and six patients with a lithium-induced urinary concentrating defect...
June 14, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28614912/peroxisome-proliferator-activated-receptor-alpha-facilitates-osteogenic-differentiation-in-mc3t3-e1-cells-via-the-sirtuin-1-dependent-signaling-pathway
#20
Kai Gong, Bo Qu, Cairu Wang, Jingsong Zhou, Dongfa Liao, Wei Zheng, Xianming Pan
Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disease characterized by a lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a NAD+-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) gamma. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPARbeta/δ- dependent manner...
June 14, 2017: Molecules and Cells
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