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https://www.readbyqxmd.com/read/29138805/extracellular-polysaccharides-purified-from-aureobasidium-pullulans-sm%C3%A2-2001-polycan-inhibit-dexamethasone%C3%A2-induced-muscle-atrophy-in-mice
#1
Jong-Min Lim, Young Joon Lee, Hyung-Rae Cho, Dong-Chan Park, Go-Woon Jung, Sae Kwang Ku, Jae-Suk Choi
The present study assessed the beneficial skeletal muscle‑preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM‑2001 (Polycan) (EAP) on dexamethasone (DEXA)‑induced catabolic muscle atrophy in mice. To investigate whether EAP prevented catabolic DEXA‑induced muscle atrophy, and to examine its mechanisms of action, EAP (100, 200 and 400 mg/kg) was administered orally, once a day for 24 days. EAP treatment was initiated 2 weeks prior to DEXA treatment (1 mg/kg, once a day for 10 days) in mice...
November 10, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29134957/hunting-for-the-mutant-without-the-map-k
#2
Leon Tejwani, Janghoo Lim
In a paper recently published in Cell Research, Yu et al. identify two MAPK-related kinases, MAPK11 and HIPK3, as positive regulators of levels of mutant huntingtin protein, a toxic species highly involved in Huntington's disease (HD) pathology. The identification and validation of these kinases as therapeutic targets for knockdown in multiple relevant experimental model systems reveal novel potential approaches for treatment of HD.
November 14, 2017: Cell Research
https://www.readbyqxmd.com/read/29126931/phytochemical-allylguaiacol-exerts-a-neuroprotective-effect-on-hippocampal-cells-and-ameliorates-scopolamine-induced-memory-impairment-in-mice
#3
Hye-Sun Lim, Bu-Yeo Kim, Yu Jin Kim, Soo-Jin Jeong
Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H2O2)-treated HT22 hippocampal cells...
November 7, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29118262/stress-hormones-promote-egfr-inhibitor-resistance-in-nsclc-implications-for-combinations-with-%C3%AE-blockers
#4
Monique B Nilsson, Huiying Sun, Lixia Diao, Pan Tong, Diane Liu, Lerong Li, Youhong Fan, Alissa Poteete, Seung-Oe Lim, Kathryn Howells, Vincent Haddad, Daniel Gomez, Hai Tran, Guillermo Armaiz Pena, Lecia V Sequist, James C Yang, Jing Wang, Edward S Kim, Roy Herbst, J Jack Lee, Waun Ki Hong, Ignacio Wistuba, Mien-Chie Hung, Anil K Sood, John V Heymach
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate β2-adrenergic receptors (β2-ARs) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce interleukin-6 (IL-6) expression...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29115571/anti-inflammatory-effects-of-a-methanolic-extract-of-castanea-seguinii-dode-in-lps-induced-raw264-7-macrophage-cells
#5
Yourim Lim, Ji-Won Park, Ok-Kyoung Kwon, Jae-Won Lee, Han-Sol Lee, Sangwoo Lee, Sangho Choi, Wanyi Li, Hang Jin, Sang-Bae Han, Kyung-Seop Ahn
Castanea extracts are known to have antioxidant properties and are used as a traditional medicine in China and Asia. However, the biological activity of Castanea seguinii Dode has remained to be fully elucidated. The present study investigated the anti-inflammatory effects of a Castanea seguinii Dode methanolic extract (CSME) on lipopolysaccharide-induced RAW264.7 macrophage cells. CSME inhibited the production of nitric oxide (NO) and the expression of inducible NO synthase. It also suppressed the production of the pro-inflammatory cytokines inteleukin-6 and tumor necrosis factor-α, as well as chemokine monocyte chemoattractant protein 1...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29113242/eupatolide-inhibits-the-tgf-%C3%AE-1-induced-migration-of-breast-cancer-cells-via-downregulation-of-smad3-phosphorylation-and-transcriptional-repression-of-alk5
#6
Ariundavaa Boldbaatar, Sunyi Lee, Sora Han, Ae Lee Jeong, Hye In Ka, Sumiyasuren Buyanravjikh, Jeong Hyung Lee, Jong-Seok Lim, Myung Sok Lee, Young Yang
The epithelial-mesenchymal transition (EMT) is a hallmark of cancer metastasis, and the associated molecular signaling pathways are regarded as therapeutic targets for cancer treatment. Thus, suppressing EMT with a natural chemical compound may be of therapeutic benefit. Eupatolide is a natural chemical compound extracted from the medicinal plant Inula britannica, which is used in Eastern Asia to treat bronchitis, disorders of the digestive system and inflammation. Besides the anti-inflammatory function of eupatolide, the present study found that eupatolide suppressed the migration and invasion of breast cancer cells, which was associated with the downregulation of vimentin in MDA-MB-231 cells and the upregulation of E-cadherin in MCF-7 cells...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29113063/inhibitory-effect-of-arachis-hypogaea-peanut-and-its-phenolics-against-methylglyoxal-derived-advanced-glycation-end-product-toxicity
#7
Sin Hee Park, Moon Ho Do, Jae Hyuk Lee, Minsun Jeong, Oh Kyung Lim, Sun Yeou Kim
Methylglyoxal (MGO) is a highly reactive dicarbonyl compound that causes endothelial dysfunction and plays important roles in the development of diabetic complications. Peanuts are rich in energy, minerals, and antioxidants. Here, we report the potential beneficial effects of peanuts, and particularly the phenolic contents, against MGO-mediated cytotoxicity. Firstly, we optimized the extraction conditions for maximum yield of phenolics from peanuts by examining different processing methods and extraction solvents...
November 4, 2017: Nutrients
https://www.readbyqxmd.com/read/29111666/switching-cyclic-nucleotide-selective-activation-of-pka-holoenzyme-reveals-distinct-roles-of-tandem-cnb-domains
#8
Daniel He, Robin Lorenz, Choel Kim, Friedrich W Herberg, Chinten James Lim
The cAMP- and cGMP-dependent protein kinases (PKA and PKG) are key effectors of cyclic nucleotide signaling. Both share structural features that include tandem cyclic nucleotide-binding (CNB) domains, CNB-A and CNB-B, yet their functions are separated through preferential activation by either cAMP or cGMP. Based on structural studies and modeling, key CNB contact residues have been identified for both kinases. In this study, we explored the requirements for conversion of PKA activation from cAMP-dependent to cGMP-dependent...
November 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29100332/the-farnesoid-x-receptor-negatively-regulates-osteoclastogenesis-in-bone-remodeling-and-pathological-bone-loss
#9
Ting Zheng, Ju-Hee Kang, Jung-Sun Sim, Jung-Woo Kim, Jeong-Tae Koh, Chan Soo Shin, Hyungsik Lim, Mijung Yim
Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Since the role of FXR in osteoclast differentiation remains ill-defined, we investigated the biological function of FXR on osteoclastogenesis, using FXR-deficient mice. We demonstrated that FXR deficiency increases osteoclast formation in vitro and in vivo. First, FXR deficiency was found to accelerate osteoclast formation via down-regulation of c-Jun N-terminal kinase (JNK) 1/2 expression...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29097919/preliminary-19-f-mrs-study-of-tumor-cell-proliferation-with-3-deoxy-3-fluorothymidine-and-its-metabolite-flt-mp
#10
In Ok Ko, Ki-Hye Jung, Mi Hyun Kim, Kyeung Jun Kang, Kyo Chul Lee, Kyeong Min Kim, Insup Noh, Yong Jin Lee, Sang Moo Lim, Jung Young Kim, Ji-Ae Park
The thymidine analogue 3'-deoxy-3'-[(18)F]fluorothymidine, or [(18)F]fluorothymidine ([(18)F]FLT), is used to measure tumor cell proliferation with positron emission tomography (PET) imaging technology in nuclear medicine. FLT is phosphorylated by thymidine kinase 1 (TK1) and then trapped inside cells; it is not incorporated into DNA. Imaging with (18)F-radiolabeled FLT is a noninvasive technique to visualize cellular proliferation in tumors. However, it is difficult to distinguish between [(18)F]FLT and its metabolites by PET imaging, and quantification has not been attempted using current imaging methods...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29097144/paxillin-actions-in-the-nucleus
#11
Xiaoting Ma, Stephen R Hammes
Paxillin is a group III LIM domain protein that is best characterized as a cytoplasmic scaffold/adaptor protein that functions primarily as a mediator of focal adhesion. However, emerging studies indicate that paxillin's function s are far broader. Not only does paxillin appear to regulate cytoplasmic kinase signaling, but it also cycles between the cytoplasm and nucleus, and may be an important regulator of mRNA trafficking and subsequent translation. Herein, we provide some insights suggesting that paxillin, like its relative Hic-5, has nuclear binding partners and mediates critical processes within the nucleus, at least in part functioning as coregulator of nuclear receptors and nuclear kinases to mediate genomic signaling...
October 30, 2017: Steroids
https://www.readbyqxmd.com/read/29093638/inhibition-of-hif1%C3%AE-and-pdk-induces-cell-death-of-glioblastoma-multiforme
#12
Jiwon Esther Han, Pyung Won Lim, Chul Min Na, You Sik Choi, Joo Young Lee, Yona Kim, Hyung Woo Park, Hyo Eun Moon, Man Seung Heo, Hye Ran Park, Dong Gyu Kim, Sun Ha Paek
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia...
October 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/29093331/germinated-waxy-black-rice-ameliorates-hyperglycemia-and-dyslipidemia-in-streptozotocin-induced-diabetic-rats
#13
Hye Won Kang, Won-Chul Lim, Jin-Kyu Lee, Jin-Nyoung Ho, Eun-Jeong Lim, Hong-Yon Cho
This study aimed to examine the anti-diabetic effect of germinated waxy black rice (GWBR) using streptozotocin (STZ)-induced diabetic rats. In the diabetic rats, GWBR supplementation for 8 weeks reduced plasma blood glucose concentrations, improved glucose clearance and prevented diabetes-induced weight loss. Rats with STZ-induced diabetes who received GWBR supplementation exhibited decreased expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter (GLUT) 2 genes and proteins in the small intestine via decreases in hepatocyte nuclear factor (HNF)-1α, HNF-1β, and HNF-4α, transcriptional factors that are involved in the regulation of SGLT1 and GLUT2, compared with the rats with STZ-induced diabetes that did not receive GWBR supplements...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29082245/extrinsic-apoptosis-pathway-altered-by-glycogen-synthase-kinase-3%C3%AE-inhibitor-influences-the-net-drug-effect-on-nsc-34-motor-neuron-like-cell-survival
#14
Jee-Eun Kim, Jung Hyun Lim, Gye Sun Jeon, Je-Young Shin, Suk-Won Ahn, Seung Hyun Kim, Kwang-Woo Lee, Yoon-Ho Hong, Jung-Joon Sung
Glycogen synthase kinase-3β (GSK-3β) inhibitors have been suggested as a core regulator of apoptosis and have been investigated as therapeutic agents for neurodegenerative diseases, including amyotrophic lateral sclerosis. However, GSK-3β has an interesting paradoxical effect of being proapoptotic during mitochondrial-mediated intrinsic apoptosis but antiapoptotic during death receptor-mediated extrinsic apoptosis. We assessed the effect of low to high doses of a GSK-3β inhibitor on survival and apoptosis of the NSC-34 motor neuron-like cell line after serum withdrawal...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29080747/trip6-promotes-cell-proliferation-in-hepatocellular-carcinoma-via-suppression-of-foxo3a
#15
Wenhui Zhao, Yubin Dai, Ting Dai, Tian Xie, Xiaobo Su, Jing Li, Xiang Zhou, Kewei Meng, Xiaohui Zhao
Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29078282/rad52-phosphorylation-by-ipl1-and-mps1-contributes-to-mps1-kinetochore-localization-and-spindle-assembly-checkpoint-regulation
#16
Gyubum Lim, Won-Ki Huh
Rad52 is well known as a key factor in homologous recombination. Here, we report that Rad52 has functions unrelated to homologous recombination in Saccharomyces cerevisiae; it plays a role in the recruitment of Mps1 to the kinetochores and the maintenance of spindle assembly checkpoint (SAC) activity. Deletion of RAD52 causes various phenotypes related to the dysregulation of chromosome biorientation. Rad52 directly affects efficient operation of the SAC and accurate chromosome segregation. Remarkably, by using an in vitro kinase assay, we found that Rad52 is a substrate of Ipl1/Aurora and Mps1 in yeast and humans...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29074501/single-agent-ibrutinib-in-relapsed-or-refractory-follicular-lymphoma-a-phase-2-consortium-trial
#17
Nancy L Bartlett, Brian A Costello, Betsy R LaPlant, Stephen M Ansell, John G Kuruvilla, Craig B Reeder, Lim S Thye, Daniel M Anderson, Kilannin Krysiak, Cody Ramirez, Jing Qi, Barry A Siegel, Malachi Griffith, Obi L Griffith, Felicia Gomez, Todd A Fehniger
Most patients with follicular lymphoma experience multiple relapses necessitating subsequent lines of therapy. Ibrutinib, a Bruton tyrosine kinase inhibitor approved for the treatment of several B-cell malignancies, showed promising activity in follicular lymphoma in a Phase 1 study. We report the results of a Phase 2 trial evaluating ibrutinib in recurrent follicular lymphoma. Forty patients with recurrent follicular lymphoma were treated with ibrutinib, 560 mg/day until progression or intolerance. The primary endpoint was overall response rate...
October 26, 2017: Blood
https://www.readbyqxmd.com/read/29064398/coumestrol-epigenetically-suppresses-cancer-cell-proliferation-coumestrol-is-a-natural-haspin-kinase-inhibitor
#18
Jong-Eun Kim, Sung-Young Lee, Mi Jang, Hyo-Kyung Choi, Jong Hun Kim, Hanyong Chen, Tae-Gyu Lim, Zigang Dong, Ki Won Lee
Targeting epigenetic changes in gene expression in cancer cells may offer new strategies for the development of selective cancer therapies. In the present study, we investigated coumestrol, a natural compound exhibiting broad anti-cancer effects against skin melanoma, lung cancer and colon cancer cell growth. Haspin kinase was identified as a direct target protein of coumestrol using kinase profiling analysis. Histone H3 is a direct substrate of haspin kinase. We observed haspin kinase overexpression as well as greater phosphorylation of histone H3 at threonine 3 (Thr-3) in the cancer cells compared to normal cells...
October 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29063115/-trpv1-an-important-molecule-involved-in-the-peripheral-sensitization-during-chronic-pain-and-central-pain-modulation
#19
Ying Zhang, Yun Wang
As chronic pain is a severe problem in clinics, study of the mechanisms of chronic pain and development of novel analgesic agents is of significance. In the past decade, our lab completed a series of studies on the regulatory mechanisms of functional sensitization and membrane trafficking of transient receptor potential vanilloid type 1 (TRPV1), a key molecule involved in the development of peripheral sensitization. Our studies elucidated the important regulatory roles of several protein kinases, including PKD1 (protein kinase D1), Cdk5 (cyclin-dependent kinase 5) and LIMK (LIM-motif containing kinase), in inflammatory thermal hyperalgesia...
October 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29056294/enhanced-ampa-receptor-trafficking-mediates-the-anorexigenic-effect-of-endogenous-glucagon-like-peptide-1-in-the-paraventricular-hypothalamus
#20
Ji Liu, Kristie Conde, Peng Zhang, Varoth Lilascharoen, Zihui Xu, Byung Kook Lim, Randy J Seeley, J Julius Zhu, Michael M Scott, Zhiping P Pang
Glucagon-like Peptide 1 (GLP-1)-expressing neurons in the hindbrain send robust projections to the paraventricular nucleus of the hypothalamus (PVN), which is involved in the regulation of food intake. Here, we describe that stimulation of GLP-1 afferent fibers within the PVN is sufficient to suppress food intake independent of glutamate release. We also show that GLP-1 receptor (GLP-1R) activation augments excitatory synaptic strength in PVN corticotropin-releasing hormone (CRH) neurons, with GLP-1R activation promoting a protein kinase A (PKA)-dependent signaling cascade leading to phosphorylation of serine S845 on GluA1 AMPA receptors and their trafficking to the plasma membrane...
November 15, 2017: Neuron
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