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Discovery Medicine

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https://www.readbyqxmd.com/read/28595039/metabolic-processing-of-the-amyloid-precursor-protein-new-pieces-of-the-alzheimer-s-puzzle
#1
Eric Norstrom
Alzheimer's disease (AD) continues to be a daunting and costly challenge for research, medicine, and society. AD pathologies point toward the involvement of metabolic fragments of the amyloid precursor protein (APP) in the pathogenesis of the disease. Through sequential enzymatic processing, APP is metabolized into several potential polypeptides, including the toxic amyloid-β (Aβ) peptide. Though great progress has been made in understanding the mechanism of conventional metabolic processing of APP to yield products such as Aβ, AD remains unpreventable and irreversible at any stage...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28595038/bio-electric-field-enhancement-the-influence-on-hyaluronan-mediated-motility-receptors-in-human-breast-carcinoma
#2
Marcy C Purnell
Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28595037/plasma-apolipoprotein-a1-levels-at-diagnosis-are-independent-prognostic-factors-in-invasive-ductal-breast-cancer
#3
Xiaorong Lin, Shubin Hong, Jiefeng Huang, Yi Chen, Yufeng Chen, Zhiyong Wu
Strong evidence exists indicating that the risk of breast cancer (BC) occurrence is influenced by complex internal environmental factors, including blood lipid and lipoprotein components. However, the roles of these components in BC development and progression remain controversial. This study examined whether serial serum lipid and lipoprotein measurements were associated with breast cancer risk and whether lipoproteins had BC prognostic properties. We compared the plasma-related parameter levels, including lipid and lipoprotein levels between 299 patients with invasive ductal breast cancer, also known as invasive ductal carcinoma (IDC), and 200 healthy donors...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28595036/s100a1-promotes-cell-proliferation-and-migration-and-is-associated-with-lymph-node-metastasis-in-ovarian-cancer
#4
Tian Tian, Xukun Li, Zhen Hua, Jianlin Ma, Zhihua Liu, Hongyan Chen, Zhumei Cui
S100A1 is a calcium-binding protein belonging to the family of S100 proteins, and is highly expressed in ovarian cancer. However, its role in ovarian cancer has not yet been fully elucidated. In this study, we examined S100A1 expression in ovarian cancer tissues and normal tissue controls and analyzed the correlation between S100A1 expression and clinicopathological parameters. We found that S100A1 expression was significantly upregulated in ovarian cancer tissues compared with fallopian and normal ovarian epithelium tissues and was significantly associated with lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) stages and tumor grades...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28595035/n-methyl-d-aspartate-receptors-mediate-epilepsy-induced-axonal-impairment-and-tau-phosphorylation-via-activating-glycogen-synthase-kinase-3%C3%AE-and-cyclin-dependent-kinase-5
#5
Xi Liu, Shu Ou, Maojia Yin, Tao Xu, Teng Wang, Ying Liu, Xueying Ding, Xinyuan Yu, Jinxian Yuan, Hao Huang, Xiuhang Zhang, Xinjie Tan, Lifen Chen, Yangmei Chen
The mechanism of epilepsy-induced axonal impairment is poorly understood. N-methyl-D-aspartate receptors (NMDARs) play important roles in epilepsy and mediate structural and functional axonal impairment. GSK-3β and Cdk5 affect axons and are regulated by NMDARs, while their roles in epilepsy-induced axonal impairment are unclear. We demonstrated that axonal impairment is characterized by neurofilament heavy (NFH) reduction, amyloid precursor protein (APP) accumulation, and increased tau phosphorylation accompanied by a decrease of total tau in temporal lobe epilepsy (TLE) patients and pentylenetetrazol (PTZ)-kindled rats...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28595034/preclinical-and-clinical-studies-of-coriolus-versicolor-polysaccharopeptide-as-an-immunotherapeutic-in-china
#6
Yajing Chang, Meng Zhang, Yifei Jiang, Yong Liu, Heng Luo, Cui Hao, Pengjiao Zeng, Lijuan Zhang
Conventional cancer treatments include surgery, chemotherapy, and radiation therapy. In recent years, immunotherapy in cancer care has been gaining momentum. Interestingly, an immunotherapeutic regime that employs polysaccharopeptide (PSP), a unique peptide-containing polysaccharide isolated from Coriolus versicolor, has already become a routine clinical practice in Japan since 1977 and in China since 1987. Coriolus versicolor is one of the most well-known traditional food and medicinal mushrooms in China for thousands of years...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28472613/emerging-insights-on-the-pathogenesis-and-treatment-of-extranodal-nk-t-cell-lymphomas-enktl
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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