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https://www.readbyqxmd.com/read/28214865/inhibition-of-trpc6-signal-pathway-alleviates-podocyte-injury-induced-by-tgf-%C3%AE-1
#1
Haiting Huang, Yanwu You, Xu Lin, Chunrong Tang, Xiangjun Gu, Meiying Huang, Youling Qin, Junhua Tan, Feifan Huang
BACKGROUND/AIMS: Transforming growth factor beta 1 (TGF-β1) plays a critical role in the pathogenesis of glomerulosclerosis. The purpose of this study was to examine the effects of inhibition of transient receptor potential cation channel C6 (TRPC6) on podocyte injury induced by TGF-β1 via nephrin and desmin mechanisms. METHODS: A rat model of nephropathy was first induced by intravenous injections of adriamycin to determine TRPC6 signal pathway engaged in glomerulosclerosis in vivo...
January 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214686/enhanced-anticancer-effect-of-combretastatin-a-4-phosphate-when-combined-with-vincristine-in-the-treatment-of-hepatocellular-carcinoma
#2
Esam M Aboubakr, Ashraf Taye, Omar M Aly, A M Gamal-Eldeen, Mohamed A El-Moselhy
Tubulin targeting agents have received considerable interest as a potential tumor-selective vascular disrupting agents, which represent another avenue for cancer growing therapeutic opportunities. Hence, the present study was conducted to investigate the anti-tumor activity of Combretastatin A-4 phosphate (CA4-P) and vincristine against hepatocellular carcinoma in rats, by individual administration and in combination. In vitro study was conducted using human hepatocellular carcinoma cell lines, showed that CA4-P and vincristine have a potent cell cytotoxic and tubulin inhibitory effect...
February 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28214489/ablation-of-the-great-saphenous-vein-with-nontumescent-n-butyl-cyanoacrylate-versus-endovenous-laser-therapy
#3
İsmail Koramaz, Helin El Kılıç, Fatih Gökalp, Macit Bitargil, Nilüfer Bektaş, Ersoy Engin, Mehmet Taşkın Egici, Ahmet Kürşat Bozkurt
OBJECTIVE: The endovenous application of n-butyl cyanoacrylate (NBCA) is a new nontumescent ablation technique for the treatment of venous insufficiency. The aim of this study was to retrospectively compare an NBCA-based ablation method with endovenous laser ablation (EVLA) for the management of incompetent great saphenous veins. METHODS: Between May 2013 and August 2014, there were 339 patients with incompetent varicose veins who were treated with either the endovenous application of NBCA (VariClose Vein Sealing System [VVSS]; Biolas, Ankara, Turkey) or EVLA...
March 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#4
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28213500/inducible-t-cell-kinase-regulates-the-acquisition-of-cytolytic-capacity-and-degranulation-in-cd8-ctls
#5
Senta M Kapnick, Jane C Stinchcombe, Gillian M Griffiths, Pamela L Schwartzberg
Patients with mutations in inducible T cell kinase (ITK) are susceptible to viral infections, particularly EBV, suggesting that these patients have defective function of CD8(+) CTLs. In this study, we evaluated the effects of ITK deficiency on cytolysis in murine CTLs deficient in ITK, and both human and murine cells treated with an ITK inhibitor. We find that ITK deficiency leads to a global defect in the cytolysis of multiple targets. The absence of ITK both affected CTL expansion and delayed the expression of cytolytic effectors during activation...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#6
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212884/desipramine-decreases-expression-of-human-and-murine-indoleamine-2-3-dioxygenases
#7
Alexandra K Brooks, Tiffany M Janda, Marcus A Lawson, Jennifer L Rytych, Robin A Smith, Cecilia Ocampo-Solis, Robert H McCusker
Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential...
February 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28212731/hamlet-a-protein-lipid-complex-with-broad-tumoricidal-activity
#8
REVIEW
James C S Ho, Aftab Nadeem, Catharina Svanborg
HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#9
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28211616/design-synthesis-and-biological-evaluation-of-chalcone-containing-shikonin-derivatives-as-inhibitors-of-tubulin-polymerization
#10
Han-Yue Qiu, Fang Wang, Xue Wang, Wen-Xue Sun, Jin-Liang Qi, Yan-Jun Pang, Rong-Wu Yang, Gui-Hua Lu, Xiao-Ming Wang, Yong-Hua Yang
The biological importance of microtubules in mitosis makes them an interesting target for the development of anticancer agents. In this study, a series of novel chalcone-containing shikonin derivatives was designed, synthesized, and evaluated for biological activities. Among them, derivative PMMB-259 [(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl (E)-2-(4-(3-oxo-3-(3-(trifluoromethoxy)phenyl)prop-1-en-1-yl)phenoxy)acetate] was identified as a potent inhibitor of tubulin polymerization...
February 17, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28211524/epigenetic-and-genetic-dissections-of-uv-induced-global-gene-dysregulation-in-skin-cells-through-multi-omics-analyses
#11
Yao Shen, Milda Stanislauskas, Gen Li, Deyou Zheng, Liang Liu
To elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209777/cd6-as-a-potential-target-for-treating-multiple-sclerosis
#12
Yan Li, Nora G Singer, Joy Whitbred, Michael A Bowen, David A Fox, Feng Lin
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28209403/small-molecules-that-sabotage-bacterial-virulence
#13
REVIEW
Benjamin K Johnson, Robert B Abramovitch
The continued rise of antibiotic-resistant bacterial infections has motivated alternative strategies for target discovery and treatment of infections. Antivirulence therapies function through inhibition of in vivo required virulence factors to disarm the pathogen instead of directly targeting viability or growth. This approach to treating bacteria-mediated diseases may have advantages over traditional antibiotics because it targets factors specific for pathogenesis, potentially reducing selection for resistance and limiting collateral damage to the resident microbiota...
February 13, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28209400/multidrug-resistant-enterococcal-infections-new-compounds-novel-antimicrobial-therapies
#14
REVIEW
Roel M van Harten, Rob J L Willems, Nathaniel I Martin, Antoni P A Hendrickx
Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E...
February 13, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28209123/relationships-between-longitudinal-neutrophil-to-lymphocyte-ratios-body-weight-changes-and-overall-survival-in-patients-with-non-small-cell-lung-cancer
#15
B A Derman, J N Macklis, M S Azeem, S Sayidine, S Basu, M Batus, F Esmail, J A Borgia, P Bonomi, M J Fidler
BACKGROUND: There is emerging evidence showing a significant relationship between overall survival (OS) in non-small cell lung cancer NSCLC patients and weight change during chemotherapy or chemoradiation. A high neutrophil/lymphocyte ratio (NLR) at baseline and at follow-up is associated with shorter survival in cancer patients and may be a surrogate for ongoing inflammation, implicated in cancer cachexia and tumor progression. The objective of this study is to explore potential relationships between OS, serial weights, and serial NLRs in advanced NSCLC patients receiving chemotherapy...
February 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28208772/transcriptional-and-behavioral-responses-of-zebrafish-larvae-to-microcystin-lr-exposure
#16
Eleni Tzima, Iliana Serifi, Ioanna Tsikari, Ainhoa Alzualde, Ioannis Leonardos, Thomais Papamarcaki
Microcystins are cyclic heptapeptides that constitute a diverse group of toxins produced by cyanobacteria. One of the most toxic variants of this family is microcystin-LR (MCLR) which is a potent inhibitor of protein phosphatase 2A (PP2A) and induces cytoskeleton alterations. In this study, zebrafish larvae exposed to 500 μg/L of MCLR for four days exhibited a 40% reduction of PP2A activity compared to the controls, indicating early effects of the toxin. Gene expression profiling of the MCLR-exposed larvae using microarray analysis revealed that keratin 96 (krt96) was the most downregulated gene, consistent with the well-documented effects of MCLR on cytoskeleton structure...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208668/redox-proteomics-and-platelet-activation-understanding-the-redox-proteome-to-improve-platelet-quality-for-transfusion
#17
REVIEW
Giona Sonego, Mélanie Abonnenc, Jean-Daniel Tissot, Michel Prudent, Niels Lion
Blood banks use pathogen inactivation (PI) technologies to increase the safety of platelet concentrates (PCs). The characteristics of PI-treated PCs slightly differ from those of untreated PCs, but the underlying reasons are not well understood. One possible cause is the generation of oxidative stress during the PI process. This is of great interest since reactive oxygen species (ROS) act as second messengers in platelet functions. Furthermore, there are links between protein oxidation and phosphorylation, another mechanism that is critical for cell regulation...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208648/n-butylidenephthalide-regulated-tumor-stem-cell-genes-ezh2-axl-and-reduced-its-migration-and-invasion-in-glioblastoma
#18
Ssu-Yin Yen, Hong-Meng Chuang, Mao-Hsuan Huang, Shinn-Zong Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208043/the-australasian-diabetes-data-network-first-national-audit-of-children-and-adolescents-with-type-1-diabetes
#19
Helen Phelan, Helen Clapin, Loren Bruns, Fergus J Cameron, Andrew M Cotterill, Jennifer J Couper, Elizabeth A Davis, Kim C Donaghue, Craig A Jefferies, Bruce R King, Richard O Sinnott, Elaine B Tham, Jerry K Wales, Timothy W Jones, Maria E Craig
OBJECTIVES: To assess glycaemic control, anthropometry and insulin regimens in a national sample of Australian children and adolescents with type 1 diabetes. DESIGN: Cross-sectional analysis of de-identified, prospectively collected data from the Australasian Diabetes Data Network (ADDN) registry. SETTING: Five paediatric diabetes centres in New South Wales, Queensland, South Australia, Victoria and Western Australia. PARTICIPANTS: Children and adolescents (aged 18 years or under) with type 1 diabetes of at least 12 months' duration for whom data were added to the ADDN registry during 2015...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28208018/pharmacophore-mapping-of-thienopyrimidine-based-monophosphonate-thp-mp-inhibitors-of-the-human-farnesyl-pyrophosphate-synthase
#20
Jaeok Park, Chun Yuen Leung, Alexios N Matralis, Cyrus M Lacbay, Michail Tsakos, Guillermo Fernandez De Troconiz, Albert M Berghuis, Youla S Tsantrizos
The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into non-skeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating non-skeletal diseases...
February 16, 2017: Journal of Medicinal Chemistry
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