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Discovery Medicine

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https://www.readbyqxmd.com/read/28371616/salvianolic-acid-a-protects-retinal-pigment-epithelium-from-ox-ldl-induced-inflammation-in-an-age-related-macular-degeneration-model
#1
Ke Mao, Wanting Shu, Qinghua Qiu, Qing Gu, Xingwei Wu
BACKGROUND: Salvianolic acid A (Sal A), an active monomer of Salvia miltiorrhiza, is a phenolic carboxylic acid derivative. The present study was performed to investigate the underlying mechanism of the anti-inflammation effect of Sal A, especially focusing on mTOR-KEAP1-Nrf2 and P2X7R-PKR-NLRP3 signaling pathways. METHODS: SD mice were divided into four groups: PBS, oxidized-low density lipoprotein (ox-LDL, 3 mg/kg), and ox-LDL (3 mg/kg) + Sal A (5 mg/kg) and + Sal A (10 mg/ml) groups...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28371615/mechanisms-that-synergistically-regulate-%C3%AE-secretase-processing-of-app-and-a%C3%AE-%C3%AE-protein-levels-relevance-to-pathogenesis-and-treatment-of-alzheimer-s-disease
#2
Joseph Ward, Haizhi Wang, Aleister J Saunders, Rudolph E Tanzi, Can Zhang
The pathophysiology of Alzheimer's disease (AD) is characterized by the formation of cerebral β-amyloid plaque from a small peptide amyloid-β (Aβ). Aβ is generated from the canonical amyloid-β precursor protein (APP) proteolysis pathway through β- and γ-secretases. Decreasing Aβ levels through targeting APP processing is a very promising direction in clinical trials for AD. A novel APP processing pathway was recently identified, in which η-secretase processing of APP occurs and results in the generation of the carboxy-terminal fragment-η (CTF-η or η-CTF) (Wang et al...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28371614/hypermutations-in-gliomas-a-potential-immunotherapy-target
#3
Gaetano Finocchiaro, Tiziana Langella, Cristina Corbetta, Serena Pellegatta
Checkpoint inhibitors, like ipilimumab, nivolumab, and pembrolizumab, have provided a breakthrough in cancer immunotherapy, such as in the treatment of melanoma and colorectal and lung cancer. The close relationship between the number of mutations (mutational load) and the response to checkpoint immunotherapy has been convincingly demonstrated in these cancers. Hypermutations in tumors are caused by environmental factors, like UV radiations or cigarette smoking, or by germinal mutations affecting genes of the Mismatch Repair (MMR) machinery, as in the Lynch syndrome...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28371613/developing-effective-therapeutics-for-alzheimer-s-disease-emerging-mechanisms-and-actions-in-translational-medicine
#4
Can Zhang
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. Presently there are no effective disease-modifying therapies. Although mutations in specific genes have been shown to be linked to inherited early onset form of AD, the causes of the more typical late onset form of the disease remain to be elucidated. Recently, significant effort focused on characterization of the pathology of AD has uncovered emerging mechanisms highlighting the substantial role of Aβ in disease pathogenesis, which is linked to tau pathology and neuro-inflammation...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28371612/current-experimental-models-of-burns
#5
Miao Qu, Mahtab Nourbakhsh
Burn injuries have a consistently high rate of mortality and morbidity and will remain a major health problem because burn injuries can result in repeat admissions for reconstruction and rehabilitation. Thus, addressing the pathophysiology of burns is crucial to improve both therapeutic interventions and patient care. A number of experimental burn models have been employed to study the systemic response of the whole organism and the more detailed cellular and molecular pathways affected by burns. However, an in-depth understanding and the useful application of experimental models are essential for effectively translating laboratory outcomes to clinical treatments...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28371611/antifibrotic-effects-of-tanshinol-in-experimental-hepatic-fibrosis-by-targeting-pi3k-akt-mtor-p70s6k1-signaling-pathways
#6
Ruqin Peng, Shaozhan Wang, Rong Wang, Yuanyuan Wang, Yan Wu, Yongfang Yuan
BACKGROUND AND AIMS: Tanshinol is a water-soluble bioactive monomer purified from the dried root of Salvia miltiorrhiza and has been reported to exert hepatoprotective efficacy in rodents. However, detailed knowledge remains limited about tanshinol's effects on hepatic stellate cells (HSC) functions, which play an essential role in the progression of hepatic fibrosis. Our research primarily focused on the effects of tanshinol on activation and apoptosis of HSC and further investigated PI3K/AKT/mTOR/p70S6K1 signaling pathways' participation in the pathogenesis of hepatic fibrosis in carbon tetrachloride (CCl4)-induced hepatic fibrosis...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245428/from-vision-to-reality-deploying-the-immune-system-for-treatment-of-sarcoma
#7
Breelyn A Wilky, John M Goldberg
Modern immunotherapy advances including checkpoint inhibitors and adoptive T cell therapy have created a new era of cancer treatment, with significant activities in a wide variety of hematologic and solid cancers. Sarcomas are rare and aggressive malignancies of bone and soft tissue affecting all ages of patients that are usually incurable when refractory to chemotherapy and surgery. However, a subset of patients with metastatic sarcoma will survive for years, suggesting that immune suppression of residual sarcoma cells may be effective in some cases...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245427/microbe-microbe-and-host-microbe-interactions-drive-microbiome-dysbiosis-and-inflammatory-processes
#8
Amy D Proal, Inge A Lindseth, Trevor G Marshall
An extensive microbiome comprised of bacteria, viruses, bacteriophages, and fungi is now understood to persist in nearly every human body site, including tissue and blood. The genomes of these microbes continually interact with the human genome in order to regulate host metabolism. Many components of this microbiome are capable of both commensal and pathogenic activity. They are additionally able to persist in both 'acute' and chronic forms. Inflammatory conditions historically studied separately (autoimmune, neurological and malignant) are now repeatedly tied to a common trend: imbalance or dysbiosis of these microbial ecosystems...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245426/histopathological-evidence-for-the-existence-of-primary-liver-progenitor-cell-cancer-insight-from-cancer-stem-cell-pathobiology
#9
Cheng-Maw Ho, Shu-Li Ho, Chia-Tung Shun, Po-Huang Lee, Ya-Hui Chen, Chin-Sung Chien, Hui-Ling Chen, Rey-Heng Hu
BACKGROUND: Primary liver progenitor cell cancer is a rare disease entity. Current nomenclature of primary liver cancer with prominent progenitor features is not comprehensive. This study was aimed to investigate the existence of this type of primary liver cancer and characterize it immunohistopathologically based on the emerging understanding of cancer stem cell pathobiology. METHODS: Surgical specimens from a primary liver cancer were stained with antibodies against well-defined markers of progenitor cells, stemness, and differentiation toward hepatocytes or cholangiocytes...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245425/intra-arterial-delivery-of-superparamagnetic-iron-oxide-nanoshell-and-polyvinyl-alcohol-based-chemoembolization-system-for-the-treatment-of-liver-tumor
#10
Qi Liang, Yi-Xiang Wang, Jin-Song Ding, Wei He, Ling-Ling Deng, Na Li, Yun-Jie Liao, Zhen Li, Bin Ye, Wei Wang
A superparamagnetic iron oxide (SPIO) nanoshell and polyvinyl alcohol (PVA) based chemoembolization system for anti-cancer drug doxorubicin (DOX) delivery has previously been presented. We have also previously confirmed the feasibility and safety of this multifunctional system for carrying both DOX and SPIO nanoparticles in vitro. However, the pharmacokinetic and the therapeutic efficacy of this novel drug-delivery system in vivo is not yet clear, and as such was the subject of this study. A rabbit liver tumor model was utilized, whereby the tumors were targeted by SPIO/DOX/PVA composite infused via a catheter into the hepatic arteries which supplying blood to the tumor...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245424/the-independent-predictors-of-significant-liver-histological-changes-in-chronic-hepatitis-b-virus-infection-patients-with-persistently-high-normal-or-low-normal-alanine-transaminase-levels
#11
Qiang Li, Chuan Lu, Weixia Li, Yuxian Huang, Liang Chen
OBJECTIVE: To determine the independent predictors of significant liver histological changes (SLHC) defined as inflammatory grade ≥A2 and/or fibrosis stage ≥F2 using the METAVIR scoring system in chronic hepatitis B virus (HBV) infection patients with persistently normal ALT (PNALT) levels. METHODS: We enrolled 392 chronic HBV infection patients with PNALT defined as normal ALT (≤40 IU/L) measured on at least three occasions at intervals of more than 2 months apart over a period of 12 or more months...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28245423/reduced-n-acetylglucosaminyltransferase-iii-expression-via-smad3-and-erk-signaling-in-tgf-%C3%AE-1-induced-hcc-emt-model
#12
Cuiju Mo, Tianhua Liu, Shu Zhang, Kun Guo, Meng Li, Xue Qin, Yinkun Liu
N-acetylglucosaminyltransferase III (GnT-III), encoded by the MGAT3 glycogene, is thought to be a tumor metastatic suppressor. Our previous studies found that the mRNA expression level of GnT-III decreased in a hepatocyte growth factor (HGF)-induced hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT) model. However, the molecular mechanism of GnT-III expression is unclear. In the present study, we established an HCC EMT model using the classic inducer transforming growth factor-β1 (TGF-β1) and focused on the Smad3 and Erk signaling pathways...
January 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28147220/intersections-of-pathways-involving-biotin-and-iron-relative-to-therapeutic-mechanisms-for-progressive-multiple-sclerosis
#13
Rebecca M Heidker, Mitchell R Emerson, Steven M LeVine
While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147219/preclinical-models-of-esophageal-adenocarcinoma-for-drug-development
#14
David S Liu, Cuong P Duong, Wayne A Phillips, Nicholas J Clemons
The advent of multi-omic profiling of tumors, together with the increasing affordability of high-throughput drug screening programs, has helped usher in a new era of molecular targeted therapies for many solid malignancies. However, there has been limited success in esophageal adenocarcinoma. Until recently, preclinical drug development for this cancer has been largely limited to a small number of cell line models. Now, the increasing availability of patient-derived xenografts and novel metastatic models are helping to bridge the gap between scientific discovery and patient care...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147218/role-of-gut-microbiome-in-ankylosing-spondylitis-an-analysis-of-studies-in-literature
#15
Yong-Yue Xu, Xi Tan, Yi-Ting He, Ying-Yan Zhou, Xiao-Hong He, Run-Yue Huang
OBJECTIVE: Gut microbiome is considered to be involved in the pathogenesis of ankylosing spondylitis (AS). We conducted a comprehensive literature review in this area to facilitate future research. METHODS: We searched all literature in the PubMed database from inception to July 2016. Relevant articles were chosen and analyzed by three independent investigators. RESULTS: The composition of gut microbiome in patients with AS has been identified to be different from healthy populations; however, specific profiles of gut microbiome are not yet clearly known...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147217/ccg-an-integrative-resource-of-cancer-protein-coding-genes-and-long-noncoding-rnas
#16
Mengrong Liu, Yu-Cheng T Yang, Gang Xu, Chang Tan, Zhi John Lu
The identification of cancer genes remains a main aim of cancer research. With the advances of high-throughput sequencing technologies, thousands of novel cancer genes were identified through recurrent mutation analyses and differential expression analyses between normal tissues and tumors in large populations. Many databases were developed to document the cancer genes. However, no public database providing both cancer protein-coding genes and cancer lncRNAs is available presently. Here, we present the Catalogue of Cancer Genes (CCG) database (http://ccg...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147216/an-emerging-role-of-alu-rna-in-geographic-atrophy-pathogenesis-the-implication-for-novel-therapeutic-strategies
#17
Xiying Mao, Wangyi Fang, Qinghuai Liu
It is generally accepted that geographic atrophy (GA), a currently untreatable advanced form of age-related macular degeneration (AMD), is a multifactorial disease resulting in gradual and permanent blindness. Various risk factors are demonstrated to be responsible for its pathogenesis, such as aging, light exposure, and smoking. Molecular components associated with those risk factors form a complex and interwoven network at the confluence of inflammation, highlighting the significance of inflammasome activation in GA progression...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28147215/attenuated-synovial-fluid-ghrelin-levels-are-linked-with-cartilage-damage-meniscus-injury-and-clinical-symptoms-in-patients-with-knee-anterior-cruciate-ligament-deficiency
#18
Yu-Cong Zou, Liang-Hua Chen, Yong-Liang Ye, Guang-Gang Yang, Zheng Mao, Dan-Dan Liu, Jun-Qi Chen, Jing-Jie Chen, Gang Liu
BACKGROUND: The meniscus injury and post-traumatic knee osteoarthritis (PTOA) following anterior cruciate ligament (ACL) lesions often cause great burdens to patients. Ghrelin, a recently identified 28-amino-acid peptide, has been shown to inhibit inflammation and perform as a growth factor for chondrocyte. OBJECTIVE: This study was aimed at investigating ghrelin concentration in synovial fluid and its association with the degree of meniscus injury, articular degeneration, and clinical severity in patients suffering from anterior cruciate ligament (ACL) deficiency...
December 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009972/inhibition-of-the-hedgehog-pathway-leads-to-antifibrotic-effects-in-dermal-fibrosis
#19
Hua-Li Cao, Jiong Zhou, Xi-Bei Chen, Lilla Landeck, Jian-Qiang Yang, Jia-Qi Chen, Wei Li, Sui-Qing Cai, Min Zheng, Xiao-Yong Man
Dermal fibrosis is characterized by the activation of the matrix-producing 'positive' myofibroblasts, and the relentless production and deposition of extracellular matrix. The hedgehog pathway has recently been demonstrated to work in a pro-fibrotic manner in systemic sclerosis (SSc). A negative regulator of the hedgehog pathway (Hh), the suppressor of fused (Sufu), was shown to be involved in the activation of fibrotic diseases. However, the exact role of Sufu in fibrosis has not been investigated so far. In our study, we aimed to define the role of sufu in the process of fibrosis using dermal fibroblasts of healthy donors that were cultured in vitro...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#20
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
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