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Discovery Medicine

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https://www.readbyqxmd.com/read/28472613/emerging-insights-on-the-pathogenesis-and-treatment-of-extranodal-nk-t-cell-lymphomas-enktl
#1
Bradley M Haverkos, Carrie Coleman, Alejandro A Gru, Zenggang Pan, Jonathan Brammer, Rosemary Rochford, Anjali Mishra, Christopher C Oakes, Robert A Baiocchi, Aharon G Freud, Pierluigi Porcu
Extranodal NK/T-cell lymphoma (ENKTL) is a rare aggressive extranodal non-Hodgkin lymphoma (NHL) universally associated with Epstein-Barr virus (EBV). ENKTL most commonly occurs in non-elderly immune competent males in Asia and South America. A number of antecedent lymphoproliferative disorders (LPDs) have been described in Asian and South American patients, but the majority of Caucasian ENKTL patients have no known preceding LPD or underlying immunodeficiency. Other than EBV, no environmental or extrinsic factor has been implicated in oncogenesis...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28472612/acidemia-and-blood-free-fatty-acids-analysis-of-cardiovascular-risk-factors-in-a-new-context
#2
António Heitor Reis
Following a hypothesis developed in an earlier paper, here it is discussed how deviations of blood pH from the normal range (namely states of acidemia) together with high blood levels of free fatty acids (FFA) may offer a rationale for many important risk factors for cardiovascular diseases (CVD) by shaping a context for formation of fatty acid micelles and vesicles with an acidic core, which fuse with the endothelia, disrupt vital cell processes, and thereby may initiate atherosclerotic plaque formation. Acidemia may arise primarily from dysregulation of the systemic buffers that control blood pH, chronic diseases of kidneys and lungs, inappropriate diet, or may be induced by some common drugs...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28472611/coexisting-cortical-atrophy-plays-a-crucial-role-in-cognitive-impairment-in-moderate-to-severe-cerebral-small-vessel-disease-patients
#3
Jie Tang, Langfeng Shi, Qianhua Zhao, Miaoyi Zhang, Ding Ding, Bo Yu, Jianhui Fu
Whether white matter lesion (WML) is associated with vascular cognitive impairment in cerebral small vessel disease (CSVD) remains controversial; some severe CSVD patients retain normal cognitive function, and cortical thinning associated with WMLs has also been recently reported. The contribution of cortical atrophy to vascular cognitive impairment in severe CSVD and whether WML affects cortical atrophy remain unknown. From November 2012 to January 2015, 50- to 80-year-old patients with moderate to severe WMLs or more than four lacunar infarctions and cognitive complaints, excluding those with large vascular diseases diagnosed by transcranial cerebral Doppler, were recruited...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28472610/nature-functions-and-clinical-implications-of-igg4-autoantibodies-in-systemic-lupus-erythematosus-and-rheumatoid-arthritis
#4
Qingjun Pan, Qiaofen Lan, Yanxia Peng, Jun Cai, Jian Zheng, Carol Dickerson, Haiyan Xiao, Hua-Feng Liu
Protective autoantibodies in homeostasis, clinical relevance, and therapeutic potential have gained wide attention. Recent studies showed that IgG4 autoantibodies play crucial roles in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In one aspect, IgG4 autoantibodies can bind autoantigens in competition with other classes of immunoglobulins (e.g., IgG1, IgG2a) to form non-inflammatory immune-complexes (ICs), which have a limited ability to induce immune responses because of the low affinity of IgG4 for both Fc receptors and the C1 complement molecule, resulting in reduced inflammatory response in SLE and RA...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28472609/diagnosis-of-afp-negative-early-stage-hepatocellular-carcinoma-using-fuc-pon1
#5
Hong Shu, Wei Li, Shuxin Shang, Xue Qin, Shu Zhang, Yinkun Liu
Our previous study demonstrated that Fuc-PON1 (the ratio of fucosylated serum paraoxonase 1 to the total serum serum paraoxonase 1) was increased significantly in hepatocellular carcinoma (HCC) patients with low AFP levels. Herein, a separate cohort of AFP-negative (AFP(-)) early HCC patients was studied to validate the diagnostic potential of Fuc-PON1. Aleuria aurantia lectin (AAL) ELISA and protein ELISA were measured simultaneously to calculate PON1 fucosylation at its protein level. Lens culinaris agglutinin reactive AFP (AFP-L3) and glypican-3 (GPC3) concentrations of the same specimens were also evaluated...
March 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28472608/epigenetic-regulation-of-voltage-gated-potassium-ion-channel-molecule-kv1-3-in-mechanisms-of-colorectal-cancer
#6
Tao He, Can Wang, Meiying Zhang, Xiaomei Zhang, Shufang Zheng, Enqiang Linghu, Mingzhou Guo
Colorectal cancer (CRC) is among the leading causes of cancer-related death throughout the world. Aberrant expression of voltage-gated potassium ion channel molecule Kv1.3 has been reported in various cancers. To explore the expression and regulation of Kv1.3 in colorectal cancer, 7 colorectal cancer cell lines and 147 cases of primary colorectal cancer were involved in this study. Kv1.3 was expressed in LOVO and SW480 cells and loss of expression was found in RKO, DLD1, SW620, HCT116, and HT29 cells. Complete methylation was found in RKO, DLD1, SW620, HCT116, and HT29 cells, partial methylation was found in LOVO and SW480 cells...
March 2017: Discovery Medicine
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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