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https://www.readbyqxmd.com/read/29656147/liver-fibrosis-direct-antifibrotic-agents-and-targeted-therapies
#1
REVIEW
Detlef Schuppan, Muhammad Ashfaq-Khan, Ai Ting Yang, Yong Ook Kim
Liver fibrosis and in particular cirrhosis are the major causes of morbidity and mortality of patients with chronic liver disease. Their prevention or reversal have become major endpoints in clinical trials with novel liver specific drugs. Remarkable progress has been made with therapies that efficiently address the cause of the underlying liver disease, as in chronic hepatitis B and C. Highly effective antiviral therapy can prevent progression or even induce reversal in the majority of patients, but such treatment remains elusive for the majority of liver patients with advanced alcoholic or nonalcoholic steatohepatitis, genetic or autoimmune liver diseases...
April 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29655978/sitagliptin-prevents-isoproterenol-induced-myocardial-infarction-in-rats-by-modulating-nitric-oxide-synthase-enzymes
#2
Mohamed Abdellah Ibrahim, Ayman Geddawy, Soha Abdel-Wahab
Ischemic heart disease is a common cause of mortality worldwide. Sitagliptin is a new anti-diabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor. The study investigated the ability of sitagliptin to prevent pathological changes of isoproterenol- (ISO-) induced myocardial injury in rats. The role of nitric oxide (NO) was also reported. Rats were assorted into six groups (n = 7) and treated for 12 days. Group 1: normal control, received normal saline. Group 2, sitagliptin control, received sitagliptin (10mg/kg, orally)...
April 12, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29655915/real-time-monitoring-of-ph-dependent-intracellular-trafficking-of-ovarian-cancer-g-protein-coupled-receptor-1-in-living-leukocytes
#3
Modong Tan, Satoshi Yamaguchi, Motonao Nakamura, Teruyuki Nagamune
G-protein coupled receptors (GPCRs) are involved in many diseases and important biological phenomena; elucidating the mechanisms underlying regulation of their signal transduction potentially provides both novel targets for drug discovery and insight into living systems. A proton-sensing GPCR, ovarian cancer G protein-coupled receptor 1 (OGR1), has been reported to be related to acidosis and diseases that cause tissue acidification, but the mechanism of proton-induced activation of OGR1-mediated signal transduction in acidic conditions remains unclear...
April 11, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29655699/scutellarin-protects-against-vascular-endothelial-dysfunction-and-prevents-atherosclerosis-via-antioxidation
#4
Jiao Mo, Renhua Yang, Fan Li, Xiaochao Zhang, Bo He, Yue Zhang, Peng Chen, Zhiqiang Shen
BACKGROUND: Scutellarin is the major constituent responsible for the clinical benefits of Erigeron breviscapus (Vant.) Hand.-Mazz which finds a long history of ethnopharmacological use in Traditional Chinese Medicine. Scutellarin as a pure compound is now under investigation for its protections against various tissue injuries. PURPOSE: This study aims to examine the effects of scutellarin on oxidative stress-induced vascular endothelial dysfunction and endothelial cell damage, and then to evaluate the therapeutic efficacy of scutellarin in preventing atherosclerosis in rats...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655697/leaves-of-acer-palmatum-thumb-rescues-n-ethyl-n-nitrosourea-enu-induced-retinal-degeneration-in-mice
#5
Tae Woo Oh, Hyun Ju Do, Kwang-Youn Kim, Kwang Il Park, Jin Yeul Ma
BACKGROUND: In the East Asia, the genus Acer (Aceraceae) is a herbal medicine that is used to treat various diseases, including hemostasis, hepatic disorders, traumatic bleeding and poor eyesight. However, the effects of Acer palmatum thumb. on retinal degeneration are unknown. AIM: In this study, we investigated whether Acer palmatum thumb.ethanol extract (KIOM-2015E) can protect eyes from retinal degeneration. Our research investigated whether KIOM-2015E could have a protective effect in the retinal degenerating mouse model induced by N-ethyl-N-nitrosourea (ENU)...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655684/protective-role-and-mechanism-of-snakegourd-peel-against-myocardial-infarction-in-rats
#6
Guanlin Yang, Dongyu Min, Junwei Yan, Ming Yang, Guijun Lin
BACKGROUND: Injection of snakegourd peel (SP), an herb used in traditional Chinese medicine, is used to treat coronary artery disease and stable angina in China. However, its therapeutic role and mechanism of action for the treatment of myocardial infarction (MI) is not fully understood. PURPOSE: The present study was designed to investigate the effect of SP on MI-induced cardiac injury and elucidate its underlying molecular mechanisms. METHODS: To create an in vivo model of MI, we ligated the left coronary artery of Wistar rats...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655677/an-in-vitro-and-in-vivo-study-of-a-4-herb-formula-on-the-management-of-diet-induced-metabolic-syndrome
#7
Elaine Wat, Yanping Wang, Ken Chan, Hon Wai Law, Chi Man Koon, Kit Man Lau, Ping Chung Leung, Choly Yan, Clara Bik San Lau
BACKGROUND: Metabolic syndrome is the cluster of risk factors that leads to increased episodes of cardiovascular disease (CVD). These risk factors include but are not limited to obesity, non-alcoholic fatty liver (NAFLD), dyslipidemia, and type 2 diabetes. Since the pathogenesis of metabolic syndrome has multiple metabolic origins, there is no single treatment for it. Pharmacological approaches consist of separate drugs which target at individual risk factors which pose various side effects...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29655463/proteomics-for-biomarker-identification-and-clinical-application-in-kidney-disease
#8
Lin Chen, Wei Su, Hua Chen, Dan-Qian Chen, Ming Wang, Yan Guo, Ying-Yong Zhao
Treatment effectiveness for kidney disease is limited by lack of accuracy, sensitivity, specificity of diagnostic, prognostic, and therapeutic biomarkers. The gold standard test renal biopsy along with serum creatinine and proteinuria is often necessary to establish a diagnosis, particularly in glomerular disease. Proteomics has become a powerful tool for novel biomarker discovery in kidney disease. Novel proteomics offer earlier and more accurate diagnosis of renal pathology than possible with traditional biomarkers such as serum creatinine and urine protein...
2018: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/29653302/jembrana-disease-virus-vif-antagonizes-the-inhibition-of-bovine-apobec3-proteins-through-ubiquitin-mediate-protein-degradation
#9
Xing Su, Hong Wang, Xiaohong Zhou, Zhaolong Li, Baisong Zheng, Wenyan Zhang
Viral infectivity factor (Vif) encoded by lentiviruses is essential for viral replication and escaping from antiviral activity of host defensive factors APOBEC3. Jembrana disease virus (JDV) causes an acute disease syndrome with approximately 20% case fatality rate in Bali cattle. However, the interplay mechanism between JDV Vif and Bos taurus APOBEC3 (btA3) is poorly understood. In this study, we determined that JDV Vif recruits ElonginB, ElonginC(ELOB/C), Cul2 and RBX1 but without the need of CBF-β to form E3 ubiquitin ligase and induces the degradation of btA3 proteins...
April 10, 2018: Virology
https://www.readbyqxmd.com/read/29651878/in-vivo-hypoglycemic-effect-of-kigelia-africana-lam-studies-with-alloxan-induced-diabetic-mice
#10
Stephen M Njogu, Wycliffe M Arika, Alex K Machocho, Joseph J N Ngeranwa, Eliud N M Njagi
The claims by the traditional herbal medicine practitioners that Kigelia africana has bioactivity against several diseases, including diabetes mellitus, were investigated in this study. Type I diabetes mellitus was induced in mice by intraperitoneal administration of alloxan monohydrate followed by treatment with the therapeutic doses of the aqueous and ethyl acetate leaf extract of K africana to the experimentally diabetic mice. The treatment effects were compared with the normal control, diabetic control, and diabetic control rats treated with a standard antidiabetic drugs (insulin administered intraperitoneally at 1 IU/kg body weight in 0...
January 2018: Journal of evidence-based integrative medicine
https://www.readbyqxmd.com/read/29651002/metformin-decreases-the-incidence-of-pancreatic-ductal-adenocarcinoma-promoted-by-diet-induced-obesity-in-the-conditional-krasg12d-mouse-model
#11
Hui-Hua Chang, Aune Moro, Caroline Ei Ne Chou, David W Dawson, Samuel French, Andrea I Schmidt, James Sinnett-Smith, Fang Hao, O Joe Hines, Guido Eibl, Enrique Rozengurt
Pancreatic ductal adenocarcinoma (PDAC) is a particularly deadly disease. Chronic conditions, including obesity and type-2 diabetes are risk factors, thus making PDAC amenable to preventive strategies. We aimed to characterize the chemo-preventive effects of metformin, a widely used anti-diabetic drug, on PDAC development using the KrasG12D mouse model subjected to a diet high in fats and calories (HFCD). LSL-KrasG12D/+ ;p48-Cre (KC) mice were given control diet (CD), HFCD, or HFCD with 5 mg/ml metformin in drinking water for 3 or 9 months...
April 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29650965/a-novel-autophagy-enhancer-as-a-therapeutic-agent-against-metabolic-syndrome-and-diabetes
#12
Hyejin Lim, Yu-Mi Lim, Kook Hwan Kim, Young Eui Jeon, Kihyoun Park, Jinyoung Kim, Hui-Yun Hwang, Dong Jin Lee, Haushabhau Pagire, Ho Jeong Kwon, Jin Hee Ahn, Myung-Shik Lee
Autophagy is a critical regulator of cellular homeostasis, dysregulation of which is associated with diverse diseases. Here we show therapeutic effects of a novel autophagy enhancer identified by high-throughput screening of a chemical library against metabolic syndrome. An autophagy enhancer increases LC3-I to LC3-II conversion without mTOR inhibition. MSL, an autophagy enhancer, activates calcineurin, and induces dephosphorylation/nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy gene expression...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29650255/glucocorticoid-loaded-liposomes-induce-a-pro-resolution-phenotype-in-human-primary-macrophages-to-support-chronic-wound-healing
#13
Anne Gauthier, Andreas Fisch, Klaus Seuwen, Birgit Baumgarten, Heinz Ruffner, Alexandra Aebi, Martin Rausch, Fabian Kiessling, Matthias Bartneck, Ralf Weiskirchen, Frank Tacke, Gert Storm, Twan Lammers, Marie-Gabrielle Ludwig
Glucocorticoids are well established anti-inflammatory agents, however, their use to treat chronic inflammatory diseases is limited due to a number of serious side effects. For example, long-term local treatment of chronic wounds with glucocorticoids is prohibited by dysregulation of keratinocyte and fibroblast function, leading to skin thinning. Here, we developed and tested liposome formulations for local delivery of dexamethasone to primary human macrophages, to drive an anti-inflammatory/pro-resolution phenotype appropriate for tissue repair...
April 5, 2018: Biomaterials
https://www.readbyqxmd.com/read/29649746/degradation-of-alpha-synuclein-by-dendritic-cell-factor-1-delays-neurodegeneration-and-extends-lifespan-in-drosophila
#14
Shiqing Zhang, Ruili Feng, Yanhui Li, Linhua Gan, Fangfang Zhou, Shiquan Meng, Qian Li, Tieqiao Wen
Parkinson's disease (PD) is a common neurodegenerative disease associated with the progressive loss of dopaminergic neurons in the substantia nigra. Proteinaceous depositions of alpha-synuclein (α-syn) and its mutations, A30P and A53T, are one important characteristic of PD. However, little is known about their aggregation and degradation mechanisms. Dendritic cell factor 1 (DCF1) is a membrane protein that plays important roles in nerve development in mouse. In this study, we aimed to show that DCF1 overexpression in a PD Drosophila model significantly ameliorates impaired locomotor behavior in third instar larvae and normalizes neuromuscular junction growth...
March 13, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29649591/inhalable-gadofullerenol-70-fullerenol-as-high-efficiency-ros-scavengers-for-pulmonary-fibrosis-therapy
#15
Yue Zhou, Mingming Zhen, Haijun Ma, Jie Li, Chunying Shu, Chunru Wang
Pulmonary fibrosis has become a fatal disease for its high incidence and few effective drugs available in clinic. In this study, gadofullerenol (GF-OH) and [70] fullerenol (C70 -OH) nanoparticles (NPs) prepared by a one-pot reaction were designed as nanomedicines to treat this fatal disease. It was revealed that the inhalation of gadofullerenols and [70] fullerenols substantially alleviates the collagen deposition induced by acute lung injury. Based on detailed studies of oxidative stress parameters and transforming growth factor-β1 (TGF-β1 ), we demonstrated they owned the antioxidant and anti-inflammatory functions for the modulation of ROS-mediated inflammation process...
April 9, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29644714/design-synthesis-and-biological-evaluation-of-2-substituted-2-3-4-9-tetrahydrospiro-%C3%AE-carboline-3-carboxylic-acid-derivatives-as-first-in-class-mast-cell-stabilizers
#16
Jatinder Singh, Ramanpreet Shah, Dhandeep Singh, Amteshwar S Jaggi, Nirmal Singh
Mast cell degranulation plays a momentous role in myriad diseases like asthma, eczema, allergic rhinitis, and conjunctivitis as well as anaphylactic shock; hence, there is an unmet need for developing new mast cells stabilizers. The reported mast cell stabilizers have a heterocyclic moiety and an acidic group. Furthermore, the role of tryptophan in suppression of mast cell activation is established. Hence, we prepared constrained analogs of tryptophan, which are derivatives of 2,3,4,9-tetrahydrospiro-β-carboline-3-carboxylic acid, and evaluated them for ex vivo inhibition of compound 48/80-induced mast degranulation activity...
April 12, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29644475/electrophysiologic-toxicity-of-chemoradiation
#17
REVIEW
Merna A Armanious, Shreya Mishra, Michael G Fradley
PURPOSE OF REVIEW: There is growing awareness of the link between oncology treatments and cardiovascular (CV) complications. This has led to the development of cardio-oncology, a specialty aimed at managing CV risk and disease in cancer patients and survivors. Cardiac arrhythmias are potential adverse CV complications of cancer treatments; however, these cardiotoxicities are often underappreciated due to the uncertain arrhythmogenic mechanisms of various chemotherapeutic agents. RECENT FINDINGS: Chemotherapeutic agents can induce arrhythmias via direct electrophysiological effects on ion channels or intracellular signaling pathways, or indirectly from cardiac tissue damage...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29643997/new-antimicrobial-peptide-kills-drug-resistant-pathogens-without-detectable-resistance
#18
Jong-Kook Lee, Tudor Luchian, Yoonkyung Park
Clavaspirin peptide (CSP) is derived from the pharyngeal tissues of the tunicate Styela clava . The 23-amino acid peptide is histidine-rich and amidated at the N-terminus. CSP possesses low antimicrobial and high hemolytic activity at pH 7.4. Therefore, we designed 4 CSP analogs with substituted hydrophobic amino acids to reduce hydrophobic amino acid interactions. These modifications reduced the aggregation and cytotoxicity of the analogs at pH 7.4. The analogs also showed potent antimicrobial activity by accumulating on bacterial cell surfaces and inducing the lytic mechanism against gram-negative and gram-positive cells at pH 5...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643251/pharmacological-characterization-of-iw-1973-a-novel-soluble-guanylate-cyclase-stimulator-with-extensive-tissue-distribution-anti-hypertensive-anti-inflammatory-and-anti-fibrotic-effects-in-preclinical-models-of-disease
#19
Jenny V Tobin, Daniel P Zimmer, Courtney Shea, Peter Germano, Sylvie G Bernier, Guang Liu, Kim Long, Joy Miyashiro, Sheila Ranganath, Sarah Jacobson, Kim Tang, G-Yoon Jamie Im, James Sheppeck, Joel D Moore, Kristine Sykes, James Wakefield, Renee Sarno, Ali R Banijamali, Albert T Profy, G Todd Milne, Mark G Currie, Jaime L Masferrer
Soluble guanylate cyclase (sGC), a key signal-transduction enzyme, increases the conversion of guanosine-5'-triphosphate (GTP) to cyclic guanosine-3',5'-monophosphate (cGMP) upon binding of nitric oxide (NO). Endothelial dysfunction and/or reduced NO signaling have been implicated in cardiovascular disease pathogenesis and complications of diabetes, and have been associated with other disease states and aging. sGC stimulators are small-molecule drugs that bind sGC and enhance NO-mediated cGMP signaling. The pharmacological characterization of IW-1973, a novel clinical-stage sGC stimulator, is described...
April 11, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29642963/nanoencapsulation-of-benznidazole-in-calcium-carbonate-increases-its-selectivity-to-trypanosoma-cruzi
#20
Louise Donadello Tessarolo, Ramon Róseo Paula Pessoa Bezerra de Menezes, Clarissa Perdigão Mello, Dânya Bandeira Lima, Emanuel Paula Magalhães, Eveline Matias Bezerra, Francisco Adilson Matos Sales, Ito Liberato Barroso Neto, Maria de Fátima Oliveira, Ricardo Pires Dos Santos, Eudenilson L Albuquerque, Valder Nogueira Freire, Alice Maria Martins
Chagas disease is a public health problem, affecting about 7 million people worldwide. Benznidazole (BZN) is the main treatment option, but it has limited effectiveness and can cause severe adverse effects. Drug delivery through nanoparticles has attracted the interest of the scientific community aiming to improve therapeutic options. The aim of this study was to evaluate the cytotoxicity of benznidazole-loaded calcium carbonate nanoparticles (BZN@CaCO3) on Trypanosoma cruzi strain Y. It was observed that BZN@CaCO3 was able to reduce the viability of epimastigote, trypomastigote and amastigote forms of T...
April 12, 2018: Parasitology
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