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https://www.readbyqxmd.com/read/28551771/synergistic-effects-of-chuanxiong-chishao-herb-pair-on-promoting-angiogenesis-at-network-pharmacological-and-pharmacodynamic-levels
#1
Yan Wang, Gang Guo, Bin-Rui Yang, Qi-Qi Xin, Qi-Wen Liao, Simon Ming-Yuen Lee, Yuan-Jia Hu, Ke-Ji Chen, Wei-Hong Cong
OBJECTIVE: To investigate the synergistic effects of Chuanxiong-Chishao herb-pair (CCHP) on promoting angiogenesis in silico and in vivo. METHODS: The mechanisms of action of an herb-pair, Chuanxiong- Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao...
May 27, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28551708/novel-and-experimental-therapies-in-chronic-pancreatitis
#2
REVIEW
Soumya Jagannath, Pramod Kumar Garg
Chronic pancreatitis (CP) is a progressive inflammatory disease of the pancreas. The currently available treatment of CP is aimed at controlling symptoms and managing complications. Unfortunately, no specific treatment is available to halt the progression of the disease process because the pathophysiological perturbations in CP are not well understood. In this review, we discuss various therapeutic targets and investigational agents acting on these targets. Among these, therapies modulating immune cells and those acting on pancreatic stellate cells appear promising and may translate into clinical benefit in near future...
May 27, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28551553/pentoxifylline-attenuates-cytokine-stress-and-fas-system-in-syngeneic-liver-proteins-induced-experimental-autoimmune-hepatitis
#3
Nevien Hendawy
BACKGROUND: Apoptosis is a hallmark in the pathogenesis of autoimmune hepatitis (AIH). Cytokine stresses and extrinsic apoptotic pathway have been implicated in this type of hepatic injury. Pentoxifylline plays an important role in controlling inflammation and apoptosis in different autoimmune diseases. AIM: To assess the protective effect of pentoxifylline for 30days against pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) and mediators of extrinsic apoptotic pathway involving TNF receptor 1 (TNFR1) and its ligand TNF-α and Fas receptor and its ligand (FasL) in experimental autoimmune hepatitis (EAH) model...
May 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28550595/clinical-pharmacokinetics-and-pharmacodynamics-of-colistin
#4
REVIEW
Nicolas Grégoire, Vincent Aranzana-Climent, Sophie Magréault, Sandrine Marchand, William Couet
In this review, we provide an updated summary on colistin pharmacokinetics and pharmacodynamics. Colistin is an old molecule that is frequently used as last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Colistin is a decapeptide administered either as a prodrug, colistin methanesulfonate (CMS), when used intravenously, or as colistin sulfate when used orally. Because colistin binds to laboratory materials, many experimental issues are raised and studies on colistin can be tricky...
May 26, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28550283/high-resolution-bioelectrical-imaging-of-a%C3%AE-induced-network-dysfunction-on-cmos-meas-for-neurotoxicity-and-rescue-studies
#5
Hayder Amin, Thierry Nieus, Davide Lonardoni, Alessandro Maccione, Luca Berdondini
Neurotoxicity and the accumulation of extracellular amyloid-beta1-42 (Aβ) peptides are associated with the development of Alzheimer's disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550268/improving-reproducibility-of-phenotypic-assessments-in-the-dyw-mouse-model-of-laminin-%C3%AE-2-related-congenital-muscular-dystrophy
#6
Raffaella Willmann, Heather Gordish-Dressman, Sarina Meinen, Markus A Rüegg, Qing Yu, Kanneboyina Nagaraju, Ayar Kumar, Mahasweta Girgenrath, Caroline B M Coffey, Vivian Cruz, Pam M Van Ry, Laurent Bogdanik, Cathleen Lutz, Anne Rutkowski, Dean J Burkin
Laminin-α2 related Congenital Muscular Dystrophy (LAMA2-CMD) is a progressive muscle disease caused by partial or complete deficiency of laminin-211, a skeletal muscle extracellular matrix protein. In the last decade, basic science research has queried underlying disease mechanisms in existing LAMA2-CMD murine models and identified possible clinical targets and pharmacological interventions. Experimental rigor in preclinical studies is critical to efficiently and accurately quantify both negative and positive results, degree of efficiency of potential therapeutics and determine whether to move a compound forward for additional preclinical testing...
May 24, 2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28550101/a-novel-experimental-rat-model-of-peripheral-nerve-scarring-reliably-mimicking-post-surgical-complications-and-recurring-adhesions
#7
Angela Lemke, Carina Penzenstadler, James Ferguson, Dominika Lidinsky, Rudolf Hopf, Monika Bradl, Heinz Redl, Susanne Wolbank, Thomas Hausner
Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. Furthermore, these signs can reoccur following external neurolysis, currently the most common surgical treatment, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients...
May 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28550049/recovery-of-ethanol-induced-akkermansia-muciniphila-depletion-ameliorates-alcoholic-liver-disease
#8
Christoph Grander, Timon E Adolph, Verena Wieser, Patrick Lowe, Laura Wrzosek, Benedek Gyongyosi, Doyle V Ward, Felix Grabherr, Romana R Gerner, Alexandra Pfister, Barbara Enrich, Dragos Ciocan, Sophie Macheiner, Lisa Mayr, Matthias Drach, Patrizia Moser, Alexander R Moschen, Gabriel Perlemuter, Gyongyi Szabo, Anne Marie Cassard, Herbert Tilg
OBJECTIVE: Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD. DESIGN: The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A...
May 26, 2017: Gut
https://www.readbyqxmd.com/read/28549617/hematopathological-alterations-of-major-tumor-suppressor-cascade-vital-cell-cycle-inhibitors-and-hematopoietic-niche-components-in-experimental-myelodysplasia
#9
Ritam Chatterjee, Shubhangi Gupta, Sujata Law
Myelodysplastic syndrome (MDS) is a poorly understood dreadful hematopoietic disorder that involves maturational defect and abnormalities in blood cell production leading to dysplastic changes and peripheral blood pancytopenia. The present work aims in establishing the mechanistic relationship of the expressional alterations of major tumor suppressor cascade, vital cell cycle inhibitors and hematopoietic microenvironmental components with the disease pathophysiologies. The study involves the development of N-N' Ethylnitrosourea (ENU) induced mouse model of MDS, characterization of the disease with blood film and bone marrow smear studies, scanning electron microscopic observation, mitochondrial membrane potential determination, flowcytometric analysis of osteoblastic and vascular niche components along with the expressional study of cleaved caspase-3, PCNA, Chk-2, p53, Ndn, Gfi-1, Tie-2, Sdf-1, Gsk-3β, p18 and Myt-1 in the bone marrow compartment...
May 23, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28548606/anatomical-recruitment-of-spinal-v2a-interneurons-into-phrenic-motor-circuitry-after-high-cervical-spinal-cord-injury
#10
Lyandysha Viktorovna Zholudeva, Jordyn Karliner, Kimberly J Dougherty, Michael Lane
More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. The identity of spinal interneurons involved with respiratory plasticity post-SCI, however, has remained largely unknown...
May 26, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28547076/purinergic-signaling-during-intestinal-inflammation
#11
REVIEW
Maria Serena Longhi, Alan Moss, Zhenghui Gordon Jiang, Simon C Robson
Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer...
May 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28546328/microrna-15a-16-1-antagomir-ameliorates-ischemic-brain-injury-in-experimental-stroke
#12
Xinxin Yang, Xuelian Tang, Ping Sun, Yejie Shi, Kai Liu, Sulaiman H Hassan, R Anne Stetler, Jun Chen, Ke-Jie Yin
BACKGROUND AND PURPOSE: Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. METHODS: Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1-specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion...
May 25, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28544846/genomic-dna-interactions-mechanize-peptidotoxin-mediated-anti-cancer-nanotherapy
#13
Santosh K Misra, Aaron S Schwartz-Duval, Dipanjan Pan
Host defense peptides (HDPs) are a class of evolutionarily conserved substances of the innate immune response that has been identified as major players in the defense system in many living organisms. Some of the HDPs are also referred as peptidotoxins which offer immense potential for anti-cancer therapy. However, their therapeutic potential is yet to be fully translated mainly due to their off-target toxicity. Here we show that their nano-enabled delivery may become beneficial in controlling their delivery in intra-cellular space...
May 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28544785/inhibition-of-cxcl12-cxcr4-axis-as-a-potential-targeted-therapy-of-advanced-gastric-carcinoma
#14
REVIEW
Li-Jun Xue, Xiao-Bei Mao, Li-Li Ren, Xiao-Yuan Chu
The whole outcome for patients with gastric carcinoma (GC) is very poor because most of them remain metastatic disease during survival even at diagnosis or after surgery. Despite many improvements in multiple strategies of chemotherapy, immunotherapy, and targeted therapy, exploration of novel alternative therapeutic targets is still warranted. Chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12) have been identified with significantly elevated levels in various malignancies including GC, which correlates with the survival, proliferation, angiogenesis, and metastasis of tumor cells...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544650/diverse-application-of-mri-for-mouse-phenotyping
#15
REVIEW
Yijen L Wu, Cecilia W Lo
Small animal models, particularly mouse models, of human diseases are becoming an indispensable tool for biomedical research. Studies in animal models have provided important insights into the etiology of diseases and accelerated the development of therapeutic strategies. Detailed phenotypic characterization is essential, both for the development of such animal models and mechanistic studies into disease pathogenesis and testing the efficacy of experimental therapeutics. MRI is a versatile and noninvasive imaging modality with excellent penetration depth, tissue coverage, and soft tissue contrast...
May 22, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28544128/a-pediatric-trial-of-radiation-cetuximab-followed-by-irinotecan-cetuximab-in-newly-diagnosed-diffuse-pontine-gliomas-and-high-grade-astrocytomas-a-pediatric-oncology-experimental-therapeutics-investigators-consortium-study
#16
Margaret E Macy, Mark W Kieran, Susan N Chi, Kenneth J Cohen, Tobey J MacDonald, Amy A Smith, Michael M Etzl, Michele C Kuei, Andrew M Donson, Lia Gore, Jennifer DiRenzo, Tanya M Trippett, Irina Ostrovnaya, Aru Narendran, Nicholas K Foreman, Ira J Dunkel
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. METHODS: Eligible patients of age 3-21 years had newly diagnosed DIPG or HGA...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28543283/targeting-pp2a-and-proteasome-activity-ameliorates-features-of-allergic-airway-disease-in-mice
#17
Prema M Nair, Malcolm R Starkey, Tatt Jhong Haw, Gang Liu, Jay C Horvat, Jonathan C Morris, Nikki M Verrills, Andrew R Clark, Alaina J Ammit, Philip M Hansbro
BACKGROUND: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed if enhancing PP2A activity with Fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with Bortezomib (BORT) could suppress experimental AAD...
May 24, 2017: Allergy
https://www.readbyqxmd.com/read/28542306/gene-signature-associated-with-benign-neurofibroma-transformation-to-malignant-peripheral-nerve-sheath-tumors
#18
Marta Martínez, Carlos O S Sorzano, Alberto Pascual-Montano, Jose M Carazo
Benign neurofibromas, the main phenotypic manifestations of the rare neurological disorder neurofibromatosis type 1, degenerate to malignant tumors associated to poor prognosis in about 10% of patients. Despite efforts in the field of (epi)genomics, the lack of prognostic biomarkers with which to predict disease evolution frustrates the adoption of appropriate early therapeutic measures. To identify potential biomarkers of malignant neurofibroma transformation, we integrated four human experimental studies and one for mouse, using a gene score-based meta-analysis method, from which we obtained a score-ranked signature of 579 genes...
2017: PloS One
https://www.readbyqxmd.com/read/28541760/inhibition-of-proteases-activity-in-intestine-needs-a-sustainable-acidic-environment-rather-than-a-transient
#19
Chang Xing, Jin-Feng Xing, Zhi-Qiang Ge
α-Chymotrypsin (α-CT) and trypsin are important components of the enzymatic barrier. They could degrade the therapeutic proteins and peptides, inhibit their activity consequently, and thereby reduce their oral bioavailability. Acidic agents, as one type of indirect protease inhibitors, have shown proof of concept in clinical trials. We report here the inactivated proteases due to acid influence can be reactivated immediately by environmental pH recovery regardless of how long the inactivation last. To keep the inactivation time of proteases for 4 to 5 h, we designed and prepared a sustained-release tablet containing citric acid (CA) which can effectively reduce the pH below 5...
May 25, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28540679/genome-wide-analysis-of-microrna-regulated-transcripts
#20
David Chevalier, Glen M Borchert
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by either degrading transcripts or repressing translation . Over the past decade the significance of miRNAs has been unraveled by the characterization of their involvement in crucial cellular functions and the development of disease. However, continued progress in understanding the endogenous importance of miRNAs, as well as their potential uses as therapeutic tools, has been hindered by the difficulty of positively identifying miRNA targets...
2017: Methods in Molecular Biology
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