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https://www.readbyqxmd.com/read/29156831/protective-effect-of-nsa-on-intestinal-epithelial-cells-in-a-necroptosis-model
#1
Wei Dong, Min Zhang, Yaxi Zhu, Yuanhan Chen, Xingchen Zhao, Ruizhao Li, Li Zhang, Zhiming Ye, Xingling Liang
Objective: This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF-α and Z-VAD-fmk, and the cells were treated with or without NSA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156828/the-%C3%AE-glucan-from-lentinus-edodes-suppresses-cell-proliferation-and-promotes-apoptosis-in-estrogen-receptor-positive-breast-cancers
#2
Hui Xu, Siwei Zou, Xiaojuan Xu
Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156812/correlation-of-drd2-mrna-expression-levels-with-deficit-syndrome-severity-in-chronic-schizophrenia-patients-receiving-clozapine-treatment
#3
Liang Liu, Yin Luo, Guofu Zhang, Chunhui Jin, Zhenhe Zhou, Zaohuo Cheng, Guozhen Yuan
Schizophrenia is a complex, severe, chronic psychiatric disorder, and the associated deficit syndrome is widely regarded as an important clinical aspect of schizophrenia. This study analyzed the relationship of deficit syndrome severity with the mRNA levels of members of signaling pathways that associate with the pathophysiology of schizophrenia, including the dopamine D2 receptor (DRD2), protein kinase B (AKT1), and phosphoinositide-3 kinase (PI3KCB), in peripheral blood leukocytes (PBLs) of 20 healthy controls and 19 chronic schizophrenia patients with long-term clozapine treatment...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156790/kaempferol-induces-autophagic-cell-death-of-hepatocellular-carcinoma-cells-via-activating-ampk-signaling
#4
Bing Han, Yi-Qun Yu, Qi-Lian Yang, Chun-Ying Shen, Xiao-Juan Wang
In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156787/natural-compound-bavachalcone-promotes-the-differentiation-of-endothelial-progenitor-cells-and-neovascularization-through-the-ror%C3%AE-erythropoietin-ampk-axis
#5
Shuang Ling, Rong-Zhen Ni, Yunyun Yuan, Yan-Qi Dang, Qian-Mei Zhou, Shuang Liang, Fujiang Guo, Wei Feng, Yuanyuan Chen, Katsumi Ikeda, Yukio Yamori, Jin-Wen Xu
In cardiovascular diseases, endothelial function is impaired and the level of circulating endothelial progenitor cells (EPCs) is low. This study investigated whether the natural bioactive component bavachalcone (BavaC) induces the differentiation of EPCs and neovascularization in vivo; the underlying mechanisms were also examined. We observed that the treatment of rat bone marrow-derived cells with a very low dose of BavaC significantly promoted EPC differentiation. In our hindlimb ischemia models, low-dose BavaC administered orally for 14 days stimulated the recovery of ischemic hindlimb blood flow, increased circulating EPCs, and promoted capillary angiogenesis...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156779/selecting-lncrnas-in-gastric-cancer-cells-for-directed-therapy-with-bioactive-peptides-and-chemotherapy-drugs
#6
Wenyan Han, Rui Xiao, Chuanling Zhang, Qimuge Suyila, Xian Li, Xiulan Su
Selecting lncRNAs for directed therapy with bioactive peptides and chemotherapy drugs may be an effective approach to treating gastric cancer (GC). We show genome-scale identification and characterization of differentially expressed lncRNAs in GC cells treated with a novel anti-cancer bioactive peptide (ACBP) and the chemotherapy drug oxaliplatin (ASLB). A total of 17,897 lncRNAs were identified through pairwise comparison, including 2,074 novel lncRNAs. Of those, 1,386 lncRNAs were differentially expressed (over 1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156677/overcoming-resistance-to-single-agent-therapy-for-oncogenic-braf-gene-fusions-via-combinatorial-targeting-of-mapk-and-pi3k-mtor-signaling-pathways
#7
Payal Jain, Amanda Silva, Harry J Han, Shih-Shan Lang, Yuankun Zhu, Katie Boucher, Tiffany E Smith, Aesha Vakil, Patrick Diviney, Namrata Choudhari, Pichai Raman, Christine M Busch, Tim Delaney, Xiaodong Yang, Aleksandra K Olow, Sabine Mueller, Daphne Haas-Kogan, Elizabeth Fox, Phillip B Storm, Adam C Resnick, Angela J Waanders
Pediatric low-grade gliomas (PLGGs) are frequently associated with activating BRAF gene fusions, such as KIAA1549-BRAF, that aberrantly drive the mitogen activated protein kinase (MAPK) pathway. Although RAF inhibitors (RAFi) have been proven effective in BRAF-V600E mutant tumors, we have previously shown how the KIAA1549-BRAF fusion can be paradoxically activated by RAFi. While newer classes of RAFi, such as PLX8394, have now been shown to inhibit MAPK activation by KIAA1549-BRAF, we sought to identify alternative MAPK pathway targeting strategies using clinically relevant MEK inhibitors (MEKi), along with potential escape mechanisms of acquired resistance to single-agent MAPK pathway therapies...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156607/calcium-dependent-protein-kinases-in-phytohormone-signaling-pathways
#8
REVIEW
Wuwu Xu, Wenchao Huang
Calcium-dependent protein kinases (CPKs/CDPKs) are Ca(2+)-sensors that decode Ca(2+) signals into specific physiological responses. Research has reported that CDPKs constitute a large multigene family in various plant species, and play diverse roles in plant growth, development, and stress responses. Although numerous CDPKs have been exhaustively studied, and many of them have been found to be involved in plant hormone biosynthesis and response mechanisms, a comprehensive overview of the manner in which CDPKs participate in phytohormone signaling pathways, regulating nearly all aspects of plant growth, has not yet been undertaken...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156528/actein-ameliorates-hepatic-steatosis-and-fibrosis-in-high-fat-diet-induced-nafld-by-regulation-of-insulin-and-leptin-resistant
#9
Hong-Jun Chen, Jin Liu
Insulin and leptin resistance are highly involved in metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Presently, no approved treatment is available. Actein is isolated from the rthizomes of Cimicifuga foetida, a triterpene glycoside, exhibiting important biological properties, such as anti-inflammatory, anti-cancer, and anti-oxidant activity. However, its effects on metabolic syndrome are poorly understood. The aims of the study were mainly to investigate the molecular mechanisms regulating insulin and leptin resistance, and lipogenic action of actein in high fat diet-fed mice...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156489/an-adherent-mucus-layer-attenuates-the-genotoxic-effect-of-colibactin
#10
Christian Reuter, Mona Alzheimer, Heike Walles, Tobias A Oelschlaeger
The human gastrointestinal tract is a complex ecosystem in which epithelial cells and microorganisms of the intestinal microbiota live in symbiosis. Certain members of the microbiota, in particular Escherichia coli strains of the B2 phylotype, carry the polyketide synthase (pks)-island encoding the genotoxin colibactin. Colibactin is a non-ribosomal peptide (NRP) or polyketide (PK)-NRP hybrid of still unsolved structure, which induces DNA double strand breaks (DSBs) in eukaryotic cells. However, direct contact between live bacteria and host cell is required in order to elicit these genotoxic effects...
November 20, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29156422/syndecan-1-in-mechanosensing-of-nanotopological-cues-in-engineered-materials
#11
Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29155810/regulation-of-transcription-elongation-in-response-to-osmostress
#12
Andrea Silva, Santiago Cavero, Victoria Sarah, Carme Solé, René Böttcher, Sebastián Chávez, Francesc Posas, Eulàlia de Nadal
Cells trigger massive changes in gene expression upon environmental fluctuations. The Hog1 stress-activated protein kinase (SAPK) is an important regulator of the transcriptional activation program that maximizes cell fitness when yeast cells are exposed to osmostress. Besides being associated with transcription factors bound at target promoters to stimulate transcriptional initiation, activated Hog1 behaves as a transcriptional elongation factor that is selective for stress-responsive genes. Here, we provide insights into how this signaling kinase functions in transcription elongation...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155586/deconstructing-lipid-kinase-inhibitors-by-chemical-proteomics
#13
Rebecca L McCloud, Caroline E Franks, Sean T Campbell, Benjamin W Purow, Thurl E Harris, Ku-Lung Hsu
Diacylglycerol kinases (DGKs) regulate lipid metabolism and cell signaling through ATP-dependent phosphorylation of diacylglycerol to biosynthesize phosphatidic acid. Selective chemical probes to study DGKs are currently lacking and needed to annotate isoform-specific functions of these elusive lipid kinases. Previously, we explored fragment-based approaches to discover a core fragment of DGK-alpha (DGKα) inhibitors responsible for selective binding to the DGKα active site. Here, we utilize quantitative chemical proteomics to deconstruct widely used DGKα inhibitors to identify structural regions mediating off-target activity...
November 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/29155421/characterization-of-neural-stem-cells-modified-with-hypoxia-neuron-specific-vegf-expression-system-for-spinal-cord-injury
#14
Y Yun, J Oh, Y Kim, G Kim, M Lee, Y Ha
Spinal cord injury (SCI) is an incurable disease causing an ischemic environment and functional defect, thus a new therapeutic approach is needed for SCI treatment. Vascular endothelial growth factor (VEGF) is a potent therapeutic gene to treat SCI via angiogenesis and neuroprotection, and both tissue-specific gene expression and high gene delivery efficiency are important for successful gene therapy. Here we design the hypoxia/neuron dual-specific gene expression system (pEpo-NSE) and efficient gene delivery platform can be achieved by the combination ex vivo gene therapy with erythropoietin (Epo) enhancer, neuron-specific enolase (NSE) promoter and neural stem cells (NSCs)...
November 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29155392/green-synthesised-zinc-oxide-nanostructures-through-periploca-aphylla-extract-shows-tremendous-antibacterial-potential-against-multidrug-resistant-pathogens
#15
Fazal Abbas, Qaisar Maqbool, Mudassar Nazar, Nyla Jabeen, Syed Zaheer Hussain, Sadaf Anwaar, Nasir Mehmood, Muhammad Saleem Sheikh, Talib Hussain, Sidra Iftikhar
To grapple with multidrug resistant bacterial infections, implementations of antibacterial nanomedicines have gained prime attention of the researchers across the globe. Nowadays, zinc oxide (ZnO) at nano-scale has emerged as a promising antibacterial therapeutic agent. Keeping this in view, ZnO nanostructures (ZnO-NS) have been synthesised through reduction by P. aphylla aqueous extract without the utilisation of any acid or base. Structural examinations via scanning electron microscopy (SEM) and X-ray diffraction have revealed pure phase morphology with highly homogenised average particle size of 18 nm...
December 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29155359/4-methylthio-3-butenyl-isothiocyanate-mediates-nuclear-factor-erythroid-derived-2-like-2-activation-by-regulating-reactive-oxygen-species-production-in-human-esophageal-epithelial-cells
#16
Tadashi Hirata, Young-Man Cho, Isamu Suzuki, Takeshi Toyoda, Jun-Ichi Akagi, Yasushi Nakamura, Satoshi Numazawa, Kumiko Ogawa
4-Methylthio-3-butenyl isothiocyanate (MTBITC) extracted from daikon (Raphanus sativus), which shows antimutagenicity, may have applications as an effective chemopreventive agent in several cancers; however, few reports have described the associated mechanisms. We investigated whether MTBITC induced cytoprotective genes, including phase II enzymes, in Het-1A human esophageal epithelial cells. HMOX1, NQO1, and GCLC mRNA levels and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein levels were increased in Het-1A cells exposed to 10 μM MTBITC...
November 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29155327/expression-profiles-of-the-p38-mapk-signaling-pathway-from-chinese-shrimp-fenneropenaeus-chinensis-in-response-to-viral-and-bacterial-infections
#17
Yuying He, Wanlong Yao, Ping Liu, Jian Li, Qingyin Wang
Mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in cellular response to inflammatory cytokines, environmental stress and pathogenic infection, However, compared with mammals and insects, the potential function of p38 MAPK from Chinese shrimp (Fenneropenaeus chinensis) in response to viruses and bacterial infection is limited. In the study, the immune responses of four genes MKK3, MKK4, p38 and ATF-2 from F. chinensis were investigated in defending against white spot syndrome virus (WSSV), Vibrio anguillarum (V...
November 16, 2017: Gene
https://www.readbyqxmd.com/read/29155323/the-role-of-p2x7r-erk-signaling-in-dorsal-root-ganglia-satellite-glial-cells-in-the-development-of-chronic-postsurgical-pain-induced-by-skin-muscle-incision-and-retraction-smir
#18
Jingnian Song, Yanlu Ying, Wei Wang, Xianguo Liu, Xuebing Xu, Xuhong Wei, Xiangcai Ruan
The mechanisms of chronic postsurgical pain remain to be elucidated.. We reported here that skin/muscle incision and retraction (SMIR), a rat model of postsurgical pain, phosphorylated the extracellular regulated protein kinases (ERK) signaling components c-Raf, MEK (ERK kinase) and ERK1/2 in lumbar 3 dorsal root ganglion (L3 DRG) in rats. Intrathecal injection of ERK specific inhibitor SCH772984 suppressed the mechanical allodynia induced by SMIR. Further more, SMIR upregulated tumor necrosis factor alpha (TNFα) in L3 DRG, which could be inhibited by SCH772984...
November 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29155261/the-phosphodiesterase-4-inhibitor-fcpr16-attenuates-ischemia-reperfusion-injury-in-rats-subjected-to-middle-cerebral-artery-occlusion-and-reperfusion
#19
Jiajia Chen, Hui Yu, Jiahong Zhong, Hongfang Feng, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Chang Huang, Zhongzhen Zhou, Wenhua Zheng, Jiangping Xu
Current phosphodiesterase-4 (PDE4) inhibitors exert beneficial effects in central nervous system diseases via anti-inflammatory and anti-apoptotic properties, but many of them are plagued by side effects like nausea and emesis. FCPR16, a novel PDE4 inhibitor synthesized in our lab, has potential anti-inflammatory property. In the present study, we aimed to investigate the effects of FCPR16 in a rat model of ischemic stroke and evaluate its emetogenic potential. Our results showed that FCPR16 treatment improved neurological function, reduced cerebral infarct volume, and attenuated brain histological changes in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R)...
November 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29155213/human-umbilical-vein-endothelium-derived-exosomes-play-a-role-in-foetoplacental-endothelial-dysfunction-in-gestational-diabetes-mellitus
#20
Tamara Sáez, Rocío Salsoso, Andrea Leiva, Fernando Toledo, Paul de Vos, Marijke Faas, Luis Sobrevia
Gestational diabetes mellitus (GDM) characterizes by foetoplacental endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) from women with GDM show increased L-arginine transport via the human cationic amino acid transporter 1 (hCAT-1). Moreover, expression of endothelial nitric oxide synthase (eNOS) and nitric oxide synthesis are increased. Exosomes are increased in maternal plasma from GDM. We evaluated the role of foetoplacental endothelial exosomes on endothelial dysfunction in GDM. Exosomes were isolated from HUVECs from normal (ExN) and GDM (ExGDM) pregnancies...
November 15, 2017: Biochimica et Biophysica Acta
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