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https://www.readbyqxmd.com/read/29330340/the-adiponectin-receptor-agonist-adiporon-ameliorates-diabetic-nephropathy-in-a-model-of-type-2-diabetes
#1
Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes...
January 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29329879/mir-134-modulates-chronic-stress-induced-structural-plasticity-and-depression-like-behaviors-via-downregulation-of-limk1-cofilin-signaling-in-rats
#2
Cuiqin Fan, Xiuzhi Zhu, Qiqi Song, Peng Wang, Zhuxi Liu, Shu Yan Yu
Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC)...
January 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29319206/butyl-paraben-promotes-apoptosis-in-human-trophoblast-cells-through-increased-oxidative-stress-induced-endoplasmic-reticulum-stress
#3
Changwon Yang, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Butyl paraben (BP) has antimicrobial effects and is widely used as a preservative in cosmetics, foods, and pharmaceuticals. It is also absorbed into various tissues of the human body. It is known that BP is measurable in maternal and fetal tissues during pregnancy, but the effects of BP on placental development, essential for maintaining normal pregnancy, are unclear. Therefore, we investigated the effect of BP on the proliferation, apoptosis, and invasiveness of human trophoblast cells, using an HTR8/SVneo cell line...
January 10, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29319181/the-small-gtpase-rhoa-regulates-the-limk1-2-cofilin-pathway-to-modulate-cytoskeletal-dynamics-in-oocyte-meiosis
#4
Xing Duan, Yu Zhang, Kun-Lin Chen, Hao-Lin Zhang, Lan-Lan Wu, Hong-Lin Liu, Zhen-Bo Wang, Shao-Chen Sun
LIM kinases (LIMK1/2) are LIM domain-containing serine/threonine/tyrosine kinases that mediate multiple cellular processes in mitosis. In the present study, we explored the functional roles and potential signaling pathway of LIMK1/2 during mouse oocyte meiosis. Disruption of LIMK1/2 activity and expression significantly decreased oocyte polar body extrusion. Live-cell imaging revealed that spindle migration was disturbed after both LIMK1 and LIMK2 knock down, and this might be due to aberrant distribution of actin filaments in the oocyte cytoplasm and cortex...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29315579/muscle-molecular-adaptations-to-endurance-exercise-training-are-conditioned-by-glycogen-availability-a-proteomics-based-analysis-in-the-mcardle-mouse-model
#5
Carmen Fiuza-Luces, Alejandro Santos-Lozano, Francisco Llavero, Rocío Campo, Gisela Nogales-Gadea, Jorge Díez Bermejo, Carlos Balandrón, África González-Murillo, Joaquín Arenas, Miguel A Martín, Antoni L Andreu, Tomàs Pinós, Beatriz G Gálvez, Juan A López, Jesús Vázquez, José L Zugaza, Alejandro Lucia
McArdle disease is an inborn disorder of skeletal muscle glycogen metabolism that results in blockade of glycogen breakdown due to mutations in the myophosphorylase gene. We recently developed a mouse model carrying the homozygous p.R50X common human mutation (McArdle mouse), facilitating the study of how glycogen availability affects muscle molecular adaptations to endurance exercise training. Using quantitative differential analysis by liquid chromatography with tandem-mass spectrometry, we analysed the quadriceps muscle proteome of 16-week-old McArdle (n = 5) and wild-type (WT) (n = 4) mice previously subjected to 8-week moderate-intensity treadmill training or to an equivalent control (no training) period...
January 7, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29314619/naringin-protects-pancreatic-%C3%AE-cells-against-oxidative-stress-induced-apoptosis-by-inhibiting-both-intrinsic-and-extrinsic-pathways-in-insulin-deficient-diabetic-mice
#6
Ye Jin Lim, Jung Ho Kim, Jeong Hoon Pan, Jae Kyeom Kim, Tae-Sik Park, Young Jun Kim, Jin Hyup Lee, Jun Ho Kim
SCOPE: Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear. METHODS AND RESULTS: To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ)...
January 4, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29305532/lrrk2-g2019s-induces-anxiety-depression-like-behavior-prior-to-the-onset-of-motor-dysfunction-with-5-ht1a-receptor-upregulation-in-mice
#7
Juhee Lim, Yeojin Bang, Jong-Hyun Choi, Arum Han, Min-Soo Kwon, Kwang Hyeon Liu, Hyun Jin Choi
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD). The neuropathology of LRRK2 mutation-related PD is indistinguishable from that of idiopathic PD, including increased dopaminergic neurodegeneration and Lewy bodies, but its subtle non-motor phenotypes have not been fully evaluated. In the present study, we examined anxiety/depression-like behaviors and accompanying neurochemical changes in differently aged transgenic (Tg) mice expressing human mutant LRRK2 G2019S...
January 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29301607/force-mediated-proinvasive-matrix-remodeling-driven-by-tumor-associated-mesenchymal-stem-like-cells-in-glioblastoma
#8
Eun-Jung Lim, Yongjoon Suh, Seungmo Kim, Seok-Gu Kang, Su-Jae Lee
In carcinoma, cancer-associated fibroblasts participate in force-mediated extracellular matrix (ECM) remodeling, consequently leading to invasion of cancer cells. Likewise, the ECM remodeling actively occurs in glioblastoma (GBM) and the consequent microenvironmental stiffness is strongly linked to migration behavior of GBM cells. However, in GBM the stromal cells responsible for force-mediated ECM remodeling remain unidentified. We show that tumor-associated mesenchymal stem-like cells (tMSLCs) provide a proinvasive matrix condition in GBM by force-mediated ECM remodeling...
January 5, 2018: BMB Reports
https://www.readbyqxmd.com/read/29295560/fascaplysin-sensitizes-anti-cancer-effects-of-drugs-targeting-akt-and-ampk
#9
Taek-In Oh, Jun Ho Lee, Seongman Kim, Taek-Jin Nam, Young-Seon Kim, Byeong Mo Kim, Woo Jong Yim, Ji-Hong Lim
Fascaplysin, a natural product isolated from marine sponges, is a potential candidate for the development of anti-cancer drugs. However, the mechanism underlying its therapeutic effect of strengthening anti-cancer efficacy of other drugs is poorly understood. Here, we found that fascaplysin increases phosphorylation of protein kinase B (PKB), also known as AKT, and adenosine monophosphate-activated protein kinase (AMPK), which are considered therapeutic targets for cancer treatment due to their anti-apoptotic or pro-survival functions in cancer...
December 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29290252/immune-checkpoint-inhibitors-in-epidermal-growth-factor-receptor-mutant-non-small-cell-lung-cancer-current-controversies-and-future-directions
#10
REVIEW
Ross A Soo, Sun Min Lim, Nicholas L Syn, Rebecca Teng, Richie Soong, Tony S K Mok, Byoung Chul Cho
Major advances with the development of epidermal growth factor receptor tyrosine kinase inhibitors and immune check-point inhibitors have ushered in a new era in lung cancer therapy. Whilst pre-clinical studies suggest EGFR-driven NSCLC inhibit antitumor immunity through the activation of the PD-1/PD-L1 pathway, epidemiology studies suggest EGFR mutant NSCLC are more likely to have decreased PD-L1 expression. The superiority of single agent PD-1/PD-L1 inhibitors over docetaxel in pre-treated EGFR mutant NSCLC appears to be moderated...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29285287/mertk-inhibition-by-rxdx-106-in-mertk-activated-gastric-cancer-cell-lines
#11
Jung Eun Kim, Youjin Kim, Gary Li, Seung Tae Kim, Kyung Kim, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Hyuk Lee, Tae Sung Sohn, Kyoung-Mee Kim, Won Ki Kang, Jeeyun Lee
RXDX-106 is a potent and selective type II pseudo-irreversible (slow off-rate) inhibitor of TYRO3, AXL, MER and c-MET. MER tyrosine kinase (MerTK) is expressed in a variety of malignancies, including gastric cancer (GC). The oncogenic potential of MerTK is supported by various lines of evidence. First, we surveyed 10 GC cell lines for MerTK protein overexpression and MerTk phosphorylation. We next evaluated the change of downstream signaling molecules including (p)-ERK and (p)-AKT, following RXDX-106 treatment...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274036/synthesis-characterization-biological-evaluation-and-molecular-docking-studies-of-2-1h-benzo-d-imidazol-2-ylthio-n-substituted-4-oxothiazolidin-3-yl-acetamides
#12
Snehlata Yadav, Balasubramanian Narasimhan, Siong M Lim, Kalavathy Ramasamy, Mani Vasudevan, Syed Adnan Ali Shah, Manikandan Selvaraj
BACKGROUND: A series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line...
December 22, 2017: Chemistry Central Journal
https://www.readbyqxmd.com/read/29260547/cognitive-improving-effects-by-highbush-blueberry-vaccinium-crymbosum-l-vinegar-on-scopolamine-induced-amnesia-mice-model
#13
Seong Min Hong, Kyong Hee Soe, Taek Hwan Lee, In Sook Kim, Young Min Lee, Beong Ou Lim
The present study aimed to evaluate the preventive effects of highbush blueberry (Vaccinium corymbosum L.) vinegar (BV) on cognitive functions in a scopolamine (Sco)-induced amnesia model in mice. In this study, Sco (1 mg/kg, intraperitoneal injection) was used to induce amnesia. ICR mice were orally administered donepezil (5 mg/kg), blueberry extract (120 mg/kg), and BV (120 mg/kg) for 7 days. After inducing cognitive impairment by Sco, a behavioral assessment using behavior tests (i.e., Y-maze and passive avoidance tests) was performed...
December 20, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29247541/nocturnal-activation-of-melatonin-receptor-type-1-signaling-modulates-diurnal-insulin-sensitivity-via-regulation-of-pi3k-activity
#14
Sharon Owino, Aida Sánchez-Bretaño, Cynthia Tchio, Erika Cecon, Angeliki Karamitri, Julie Dam, Ralf Jockers, Giuseppe Piccione, Hye Lim Noh, Taekyoon Kim, Jason K Kim, Kenkichi Baba, Gianluca Tosini
Recent genetic studies have highlighted the potential involvement of melatonin receptor 1 (MT1 ) and melatonin receptor 2 (MT2 ) in the pathogenesis of type 2 diabetes. Here we report that mice lacking MT1 (MT1 KO) tend to accumulate more fat mass than WT mice and exhibit marked systemic insulin resistance. Additional experiments revealed that the main insulin signaling pathway affected by the loss of MT1 was the activation of phosphatidylinositol-3-kinase (PI3K). Transcripts of both catalytic and regulatory subunits of PI3K were strongly down-regulated within MT1 KO mice...
December 16, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29244751/spirulina-extract-enhanced-a-protective-effect-in-type-1-diabetes-by-anti-apoptosis-and-anti-ros-production
#15
Jiyeong Lee, Arum Park, Mi Jeong Kim, Hee-Joung Lim, Young-Ah Rha, Hee-Gyoo Kang
Interest in the nutritional value and pharmacological activities of blue-green algae has gradually increased. Spirulina extracts show protective effects against apoptosis and inflammatory damage in various cell types. Here, we investigated the protective effects of extracts from Spirulina maxima in a cytokine-mediated type 1 diabetes model in vitro and in streptozotocin-induced diabetic Wistar rats in vivo. Interleukin-1β and interferon-gamma induced substantial cytotoxicity to RINm5F rat insulinoma cells, increasing nitric oxide (NO) production, nuclear factor-kappa B (NF-κB) activity, the expression of endoplasmic reticulum (ER) stress genes, and activation of mitogen-activated protein kinases and key genes related apoptosis...
December 15, 2017: Nutrients
https://www.readbyqxmd.com/read/29239661/enhancement-of-the-antimycobacterial-activity-of-macrophages-by-ajoene
#16
Ji-Ae Choi, Soo-Na Cho, Yun-Ji Lim, Junghwan Lee, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Ajoene, a garlic-derived sulfur-containing compound, has broad-spectrum antimicrobial activity. To assess the potential of ajoene for treating tuberculosis (TB), we determined whether it induces the stress response of the endoplasmic reticulum (ER), which plays an important role in TB. We showed that ajoene stimulation induced the production of ER stress sensor molecules and reactive oxygen species (ROS) levels. Ajoene-induced ROS production was dependent on c-Jun N-terminal kinase (JNK) activation. Interestingly, the inhibition of JNK activity and suppression of ROS production reduced ajoene-induced CHOP production in macrophages...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29233185/phosphoproteomics-reveals-network-rewiring-to-a-pro-adhesion-state-in-annexin-1-deficient-mammary-epithelial-cells
#17
Asfa Alli-Shaik, Sheena Wee, Lina H K Lim, Jayantha Gunaratne
BACKGROUND: Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulation of ANXA1 functions has been associated with tumorigenesis and metastasis events in several types of cancer. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized that ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells...
December 12, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29228560/mertk-is-a-novel-therapeutic-target-in-gastric-cancer
#18
Jun Ho Yi, Jiryeon Jang, Jeonghee Cho, In-Gu Do, Mineui Hong, Seung Tae Kim, Kyoung-Mee Kim, Sujin Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Won Ki Kang, Ho Yeong Lim, Jeeyun Lee
Introduction: The role of MerTK has not been assessed in gastric cancer (GC). The aim of this study was to identify a subgroup of GC patients with MerTK tumor overexpression, and to evaluate MerTK as a potential therapeutic target in this disease. Methods: Protein and mRNA expression of MerTK were evaluated, and other various in vitro analyses including shRNA transfection, cell cycle anslysis, MTS assay and colony forming assay were carried out with GC cell lines and GC patient-derived cells (PDCs)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222344/trip6-inhibits-hippo-signaling-in-response-to-tension-at-adherens-junctions
#19
Shubham Dutta, Sebastian Mana-Capelli, Murugan Paramasivam, Ishani Dasgupta, Heather Cirka, Kris Billiar, Dannel McCollum
The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here, we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension...
December 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29219221/improved-developmental-competence-in-embryos-treated-with-lycopene-during-in-vitro-culture
#20
M M R Chowdhury, Ayman Mesalam, Imran Khan, Myeong-Don Joo, Kyeong-Lim Lee, Lianguang Xu, Fahmida Afrin, Il-Keun Kong
In vitro embryo development remains suboptimal compared to in vivo development due to the challenge from various stressors associated with in vitro culturing of oocytes. When 0.2 μM lycopene was added to oocyte in vitro maturation and embryo culture media, to assess its antioxidant effects on embryo development, we observed a significant (p<0.05) increase in cleavage and blastocyst development rates compared to the corresponding controls (84.3 ± 0.6% vs. 73.1 ± 1.9% and 41.0 ± 1.4% vs. 33.4 ± 0.7%, respectively)...
December 8, 2017: Molecular Reproduction and Development
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