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https://www.readbyqxmd.com/read/29790115/n-2-hydroxyphenyl-acetamide-and-its-gold-nanoparticle-conjugation-prevent-glycerol-induced-acute-kidney-injury-by-attenuating-inflammation-and-oxidative-injury-in-mice
#1
Rehan Ahmed Siddiqui, Shabana Usman Simjee, Nurul Kabir, Muhammad Ateeq, M Raza Shah, Syed Saad Hussain
The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury (AKI) in mice was investigated. NA-2 (50 mg/kg) and NA-2-AuNPs (30 mg/kg) were given to the animals for four days followed by 24-h water deprivation and injection of 50% glycerol (10 ml/kg im). The animals were sacrificed on the next day. Blood and kidneys were collected for biochemical investigations (urea and creatinine), histological studies (hematoxylin and eosin; and periodic acid-Schiff staining), immunohistochemistry (actin and cyclooxygenase-2, Cox-2), and real-time RT-PCR (inducible nitric oxide synthase, iNOS; nuclear factor-κB p50, NFκB; hemeoxygenase-1, HO-1; and kidney injury molecule-1, Kim-1)...
May 22, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29788141/a-single-nucleotide-polymorphism-in-the-vitamin-d-receptor-gene-is-associated-with-decreased-levels-of-the-protein-and-a-penetrating-pattern-in-crohn-s-disease
#2
Laura Gisbert-Ferrándiz, Pedro Salvador, Dolores Ortiz-Masiá, Dulce Carolina Macías-Ceja, Samuel Orden, Juan Vicente Esplugues, Sara Calatayud, Joaquín Hinojosa, Maria Dolores Barrachina, Carlos Hernández
Background: Vitamin D signaling modulates inflammation through the vitamin D receptor (VDR). The synonymous single nucleotide polymorphism (SNP) rs731236, located in the VDR gene, has been associated with a higher risk of Crohn's disease (CD). We analyzed differences in VDR expression levels among CD patients who were homozygous for allelic variants in this SNP and their relevance for disease course. Methods: DNA was extracted from blood samples of CD patients, and SNP genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism...
May 18, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29787756/fibronectin-type-iii-domain-containing-4-attenuates-hyperlipidemia-induced-insulin-resistance-via-suppression-of-inflammation-and-er-stress-through-ho-1-expression-in-adipocytes
#3
Wonjae Lee, Subin Yun, Geum Hee Choi, Tae Woo Jung
Although Fibronectin Type III Domain Containing 4 (FNDC4) has been reported to be involved in the modulation of inflammation in macrophages, its effects on inflammation and insulin resistance in adipose tissue are unknown. In the current study, we investigated the effects of FNDC4 on hyperlipidemia-mediated endoplasmic reticulum (ER) stress, inflammation, and insulin resistance in adipocytes via the AMP-activated protein kinase (AMPK)/heme oxygenase-1 (HO-1)-mediated pathway. Hyperlipidemia-induced nuclear factor κB (NFκB), inhibitory κBα (IκBα) phosphorylation, and pro-inflammatory cytokines such as TNFα and MCP-1 were markedly mitigated by FNDC4...
May 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29786867/growth-hormone-releasing-hormone-antagonists-reduce-prostatic-enlargement-and-inflammation-in-carrageenan-induced-chronic-prostatitis
#4
Petra Popovics, Renzhi Cai, Wei Sha, Ferenc G Rick, Andrew V Schally
BACKGROUND: Inflammation plays a key role in the etiology of benign prostatic hyperplasia (BPH) through multiple pathways involving the stimulation of proliferation by cytokines and growth factors as well as the induction of the focal occurrence of epithelial-to-mesenchymal transition (EMT). We have previously reported that GHRH acts as a prostatic growth factor in experimental BPH and in autoimmune prostatitis models and its blockade with GHRH antagonists offer therapeutic approaches for these conditions...
May 21, 2018: Prostate
https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#5
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29779087/down-regulation-of-mdr1-by-ad-dkk3-via-akt-nf%C3%AE%C2%BAb-pathways-augments-the-anti-tumor-effect-of-temozolomide-in-glioblastoma-cells-and-a-murine-xenograft-model
#6
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, Keiko T Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro, Yasushi Takagi
BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29775473/na-k-atpase-signaling-mediates-mir-29b-3p-regulation-and-cardiac-fibrosis-formation-in-mice-with-chronic-kidney-disease
#7
Christopher A Drummond, Xiaoming Fan, Steven T Haller, David J Kennedy, Jiang Liu, Jiang Tian
The Na/K-ATPase is an important membrane ion transporter and a signaling receptor that is essential for maintaining normal cell function. The current study examined the role of Na/K-ATPase signaling in regulating miR-29b-3p, an anti-fibrotic microRNA, in a mouse chronic kidney disease (CKD) model (5/6th partial nephrectomy or PNx). The results showed that CKD induced significant reduction of miR-29b-3p expression in the heart tissue by activation of Src and NFκB signaling in these animals. To demonstrate the role of Na/K-ATPase signaling, we also performed the PNx surgery on Na/K-ATPase α1 heterozygous (α1+/-) mice, which expresses ~40% less Na/K-ATPase α1 compared to their wild type littermates (WT) and exhibits deficiency in Na/K-ATPase signaling...
2018: PloS One
https://www.readbyqxmd.com/read/29773845/aicar-inhibits-nf%C3%AE%C2%BAb-dna-binding-independently-of-ampk-to-attenuate-lps-triggered-inflammatory-responses-in-human-macrophages
#8
Johannes Kirchner, Bernhard Brüne, Dmitry Namgaladze
5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) is an established pharmacological activator of AMP-activated protein kinase (AMPK). Both, AICAR and AMPK were reported to attenuate inflammation. However, AICAR is known for many AMPK-independent effects, although the mechanisms remain incompletely understood. Here we report a potent suppression of lipopolysaccharide (LPS)-induced inflammatory gene expression by AICAR in primary human macrophages, which occurred independently of its conversion to AMPK-activating 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl monophosphate...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773671/targeted-inhibition-of-cd74-attenuates-adipose-cox-2-mif-mediated-m1-macrophage-polarization-and-retards-obesity-related-adipose-tissue-inflammation-and-insulin-resistance
#9
Pei-Chi Chan, Ting-Ni Wu, Ying-Chuan Chen, Chieh-Hua Lu, Martin Wabitsch, Yu-Feng Tian, Po-Shiuan Hsieh
Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of COX-2/MIF-mediated crosstalk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and SVCs (stromal vascular cells) of white fat were highly correlated with body weight, HOMA-IR and adipose macrophage marker expression levels, especially those in SVCs...
May 17, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29773601/combinatorial-targeting-of-xpo1-and-flt3-exerts-synergistic-anti-leukemia-effects-through-induction-of-differentiation-and-apoptosis-in-flt3-mutated-acute-myeloid-leukemias-from-concept-to-clinical-trial
#10
Weiguo Zhang, Charlie Ly, Jo Ishizawa, Hong Mu, Vivian Ruvolo, Sharon Shacham, Naval Daver, Michael Andreeff
Targeted therapies against FLT3-mutated acute myeloid leukemia have shown limited clinical efficacy primarily because of the acquisition of secondary mutations in FLT3 and persistent activation of downstream pro-survival pathways such as MEK/ERK, PI3K/AKT, and STAT5. Activation of these additional kinases may also result in phosphorylation of tumor suppressor proteins promoting their nuclear export. Thus, co-targeting nuclear export proteins (i.e., XPO1) and FLT3 concomitantly may be therapeutically effective...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29769195/osteocyte-driven-downregulation-of-snail-restrains-effects-of-drd2-inhibitors-on-mammary-tumor-cells
#11
Shengzhi Liu, Yao Fan, Andy Chen, Aydin Jalali, Kazumasa Minami, Kazuhiko Ogawa, Harikrishna Nakshatri, Bai-Yan Li, Hiroki Yokota
While bone is a frequent target of breast cancer-associated metastasis, little is known about the effects of tumor-bone interactions on the efficacy of tumor-suppressing agents. Here we examined the effect of two FDA-approved dopamine modulators, Fluphenazine (FP) and Trifluoperazine (TFP), on mammary tumor cells, osteoclasts, osteoblasts, and osteocytes. These agents suppressed proliferation and migration of mammary tumor cells chiefly by antagonizing dopamine receptor D2 and reduced bone resorption by downregulating nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1)...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29765327/cardiovascular-adaptive-homeostasis-in-exercise
#12
Kelvin J A Davies
Adaptive Homeostasis has been defined as, "The transient expansion or contraction of the homeostatic range in response to exposure to sub-toxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events." (Davies, 2016). I propose that one of the most significant examples of adaptive homeostasis may be the adaptation of the cardiovascular system to exercise training. In particular, endurance type training involves the generation of increased levels of free radicals such as ubisemiquinone, superoxide, nitric oxide, and other (non-radical) reactive oxygen species such as hydrogen peroxide (H2 O2 ), in a repetitive manner, typically several times per week...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29765321/brain-lipopolysaccharide-preconditioning-induced-gene-reprogramming-mediates-a-tolerance-state-in-electroconvulsive-shock-model-of-epilepsy
#13
Elham Amini, Mojtaba Golpich, Abdoreza S Farjam, Behnam Kamalidehghan, Zahurin Mohamed, Norlinah M Ibrahim, Abolhassan Ahmadiani, Azman A Raymond
There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29763604/attenuation-of-macrophage-accumulation-and-polarisation-in-obese-diabetic-mice-by-a-small-molecule-significantly-improved-insulin-sensitivity
#14
Sandip Mukherjee, Snehasis Das, Dipanjan Chattopadhyay, Shuvasree Sarkar, Subhendu Kumar Chatterjee, Dhrubajyoti Talukdar, Sutapa Mukherjee, Subeer S Majumder, Satinath Mukhopadhyay, Mihir K Chaudhuri, Samir Bhattacharya
Accumulation and polarization of anti-inflammatory M2 to proinflammatory M1 macrophage in the adipose tissue of obese diabetic mice is an important pathogenic signature. It worsens lipid induced inflammation and insulin resistance. Here we demonstrate that a small molecule, a peroxyvanadate compound i.e. DmpzH [VO(O2 )2 (dmpz)] or dmp, could robustly decrease macrophage infiltration, accumulation and their polarization in high fat diet (HFD) induced obese diabetic mice. In searching the underlying mechanism it was revealed that SIRT1 level was strikingly low in the inflamed adipose tissue of HFD mice as compared to mice fed with standard diet (SD)...
May 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29763590/a-novel-mir17-protein-tyrosine-phosphatase-oc-epha4-regulatory-axis-of-osteoclast-activity
#15
REVIEW
Kin-Hing William Lau, Matilda H-C Sheng
Information about the molecular mechanisms leading to the activation of the osteoclast is relatively limited. While there is compelling evidence that the signaling mechanisms of Src and integrin β3 are essential for osteoclast activation, the regulation of these two signaling mechanisms is not fully understood. In this review, evidence supporting a novel regulatory axis of osteoclast activation that plays an upstream regulatory role in both the Src and integrin β3 signaling during osteoclast activation is discussed...
May 12, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29761875/mir-130-aggravates-acute-myocardial-infarction-induced-myocardial-injury-by-targeting-ppar-%C3%AE
#16
Xianglin Chu, Yiqing Wang, Liewen Pang, Jiechun Huang, Xiaotian Sun, Xiaofeng Chen
Cardiac remodeling is a common pathophysiological change associated with acute myocardial infarction (AMI). Recent evidence indicates that microRNAs are strong posttranscriptional regulators which play an important role in regulating the microenvironment of myocardial tissue after AMI. In this study, we sought to explore the potential role and underlying mechanism of miR-130 in AMI. H9c2 cells were cultured under hypoxic conditions to simulate myocardial infarction. The influence of aberrantly expressed miR-130 on H9c2 cells under hypoxia was also estimated with RT-PCR, western blot and enzyme-linked immunosorbent assay...
May 15, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29760187/lipopolysaccharide-lps-binding-protein-stimulates-cd14-dependent-toll-like-receptor-4-internalization-and-lps-induced-tbk1-ikk%C3%AF%C2%B5-irf3-axis-activation
#17
Hiroki Tsukamoto, Shino Takeuchi, Kanae Kubota, Yohei Kobayashi, Sao Kozakai, Ippo Ukai, Ayumi Shichiku, Misaki Okubo, Muneo Numasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Tomonori Nochi, Kouichi Watanabe, Hisashi Aso, Yoshihisa Tomioka
Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14)...
May 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29760046/dual-hdac-and-pi3k-inhibition-abrogates-nf%C3%AE%C2%BAb-and-foxm1-mediated-dna-damage-response-to-radiosensitize-pediatric-high-grade-gliomas
#18
Sharmistha Pal, David Kozono, Xiaodong Yang, Wojciech Fendler, Whitney Fitts, Jing Ni, John A Alberta, Jean Zhao, Kevin X Liu, Jie Bian, Nathalene Truffaux, William A Weiss, Adam C Resnick, Pratiti Bandopadhayay, Keith L Ligon, Steven G Dubois, Sabine Mueller, Dipanjan Chowdhury, Daphne A Haas-Kogan
Aberrant chromatin remodeling and activation of the phosphatidylinositol 3-kinase (PI3K) pathway have been identified as important mediators of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) pathogenesis. As inhibition of these pathways are promising therapeutic avenues and radiation is the only modality to prolong survival of DIPG patients, we sought to explore radiosensitizing functions of such inhibition and explore mechanisms of action of such agents. Here we demonstrate that combined treatment with radiotherapy and CUDC-907, a novel first-in-class dual inhibitor of histone deacetylases (HDAC) and PI3K, evokes a potent cytotoxic response in pHGG and DIPG models...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29759145/thymoquinone-increases-the-expression-of-neuroprotective-proteins-while-decreasing-the-expression-of-pro-inflammatory-cytokines-and-the-gene-expression-nf%C3%AE%C2%BAb-pathway-signaling-targets-in-lps-ifn%C3%AE-activated-bv-2-microglia-cells
#19
Makini K Cobourne-Duval, Equar Taka, Patricia Mendonca, Karam F A Soliman
Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil...
July 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29752864/%C3%AE-blockers-interfere-with-cell-homing-receptors-and-regulatory-proteins-in-a-model-of-spontaneously-hypertensive-rats
#20
Bruna Eibel, Melissa Kristochek, Thiago R Peres, Lucinara D Dias, Daniela R Dartora, Karina R Casali, Renato A K Kalil, Alexandre M Lehnen, Maria Claudia Irigoyen, Melissa M Markoski
AIM: To examine the interference of β-blockers with the chemokine stromal cell-derived factor-1 (SDF-1) found in cell homing receptors, C-X-C chemokine receptor type 4 (CXCR-4) and CXCR-7 and regulatory proteins of homing pathways, we administered atenolol, carvedilol, metoprolol and propranolol for 30 days using an orogastric tube to hypertensive rats. METHOD: We collected blood samples before and after treatment and quantified the levels of SDF-1 with enzyme linked immunosorbent assay (ELISA)...
May 12, 2018: Cardiovascular Therapeutics
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