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Clinical pathway

Jessica F Boehler, Marshall W Hogarth, Matthew D Barberio, James S Novak, Svetlana Ghimbovschi, Kristy J Brown, Li Alemo Munters, Ingela Loell, Yi-Wen Chen, Heather Gordish-Dressman, Helene Alexanderson, Ingrid E Lundberg, Kanneboyina Nagaraju
OBJECTIVE: To identify changes in skeletal muscle microRNA expression after endurance exercise and associate the identified microRNAs with mRNA and protein expression to disease-specific pathways in polymyositis (PM) and dermatomyositis (DM) patients. METHODS: Following a parallel clinical trial design, patients with probable PM or DM, exercising less than once a week, and on stable medication for at least one month were randomized into two groups at Karolinska University Hospital: a 12-week endurance exercise group (n = 12) or a non-exercised control group (n = 11)...
2017: PloS One
L Wei, W-Y Chen, T Hu, Y-X Tang, B-B Pan, M Jin, G-Y Kong
OBJECTIVE: Hepatic ischemia/reperfusion (I/R) injury remains to be one of the most common clinical diseases. This study aimed to explore the potential effect and mechanism of propofol in protecting rat liver from I/R injury. MATERIALS AND METHODS: The hepatic I/R model was established in Sprague-Dawley (SD) rats by perfusing the liver with heparinized cold saline through the portal vein for 20 min. The rats were then received a 100 mg/kg/d propofol administration for the continuously 10 days...
August 2017: European Review for Medical and Pharmacological Sciences
Federica Begalli, Jason Bennett, Daria Capece, Daniela Verzella, Daniel D'Andrea, Laura Tornatore, Guido Franzoso
Transcription factors of the nuclear factor κB (NF-κB) family are central coordinating regulators of the host defence responses to stress, injury and infection. Aberrant NF-κB activation also contributes to the pathogenesis of some of the most common current threats to global human health, including chronic inflammatory diseases, autoimmune disorders, diabetes, vascular diseases and the majority of cancers. Accordingly, the NF-κB pathway is widely considered an attractive therapeutic target in a broad range of malignant and non-malignant diseases...
August 22, 2017: Biomedicines
Xufang Zhang, Qingpiao Chen, Jianwei Liu, Chen Fan, Qi Wei, Zetao Chen, Xueli Mao
Periodontitis is a progressive inflammatory disease initiated by bacterial biofilm adhering to the tooth surface. If left untreated, periodontitis may lead to tooth loss and destruction of the alveolar bone. Regaining the lost alveolar bone is a clinical challenge because of the limited differentiation ability of osteoblasts in inflammatory environments. We have previously shown the anti-inflammatory and antiosteoclastogenic activities of parthenolide (PTL) in human periodontal ligament-derived cells by inhibiting nuclear factor kappa B (NF-κB) signaling, indicating its potential for periodontitis treatment...
August 22, 2017: Journal of Interferon & Cytokine Research
Aikaterini Emmanouilidi, Rossano Lattanzio, Gianluca Sala, Mauro Piantelli, Marco Falasca
Breast cancer, the most common malignancy among women, is usually detected at an early stage and has a low risk of relapse. Nevertheless, a significant number of patients cannot be cured solely by local treatment. Distinguishing between patients who are of low risk of relapse from those who are of high risk may have important implications to improve treatment outcomes. The PLC-γ1 signaling pathway promotes many physiological processes, including cell migration and invasion. Increasing evidence shows aberrant PLC-γ1 signaling implication in carcinogenesis including breast cancer...
August 22, 2017: Future Oncology
Manon Dubol, Christian Trichard, Claire Leroy, Anca-Larisa Sandu, Mehdi Rahim, Bernard Granger, Eleni T Tzavara, Laurent Karila, Jean-Luc Martinot, Eric Artiges
Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the Nucleus Accumbens, within the mesolimbic pathway. While dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown if alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in twenty-seven participants including healthy volunteers and psychiatric patients with schizophrenia, depression or cocaine addiction, using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) multimodal imaging with a voxel-based statistical approach...
August 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Saphy Sharda, Palash Sarmandal, Srinivas Bandaru, Pravin Patil, Ruchi Shukla, Amrita Jain, Anudeep Sharma, Tanmay Vyas, Tajamul Hussain, Anuraj Nayarisseri
CML originates due to reciprocal translocation in Philadelphia chromosome leading to formation of fusion product BCR-ABL which constitutively activates tyrosine kinase signaling pathways eventually abnormal proliferation of granulocytic cells. As a therapeutic strategy, BCR-ABL inhibitors have been clinically approved which terminates its phosphorylation activity and retards cancer progression. However,number of patients develops resistance to inhibitors which demand for discovery of new inhibitors. Given the drawbacks of present inhibitors, by high throughput virtual screening approaches, present study pursues to identify high affinity compounds targeting BCR-ABL1 anticipated to have safer pharmacological profiles...
August 21, 2017: Current Topics in Medicinal Chemistry
Zijuan Bi, Yu Zheng, Jianye Yuan, Zhaoxiang Bian
Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders (FBD), which is characterized by recurrent abdominal pain, abdominal bloating/distention associated with defecation or changed bowel habits. Currently, there is no evidence of obvious anatomic or physiologic abnormalities on the routine diagnostic examinations. There are multiple pathological factors involved in IBS responsible for its heterogeneous nature, although the exact etiology and pathology of IBS are not well known and it is disappointed to develop biomarkers for this disorder...
August 21, 2017: Current Pharmaceutical Design
Svetlana Vinokurova
About 15-20% of human cancers worldwide have viral etiology. Seven human DNA and RNA viruses are accepted to be oncogenic viruses or oncoviruses and contribute to the development of various cancer types. Human oncoviruses have developed multiple molecular mechanisms to interfere with specific cellular pathways to promote viral replication and viral life cycle maintenance in the host. Despite the diversity of oncogenic viruses, they use similar strategies for cancer development. Viral oncoproteins and viral non-coding RNAs are the key factors that can affect multiple cellular processes on both genetic and epigenetic levels...
August 21, 2017: Current Pharmaceutical Design
M Maccarrone, L Ulivi, N Giannini, V Montano, L Ghiadoni, R M Bruno, U Bonuccelli, M Mancuso
Common cerebral small vessel disease (cSVD) abnormalities are a common neuroradiological finding, especially in the elderly. They are associated with a wide clinical spectrum that leads to an increasing disability, impaired global function outcome and a reduced quality of life. A strong association is demonstrated with age and hypertension and other common vascular risk factors, including diabetes mellitus, dyslipoproteinemia, smoking, low vitamin B12 level, and hyperomocysteinemia. Although these epidemiological associations suggest a systemic involvement, etiopathogenetic mechanisms remain unclear...
August 21, 2017: Current Molecular Medicine
Daniela Murtas, Cristina Maxia, Andrea Diana, Luca Pilloni, Claudia Corda, Luigi Minerba, Sara Tomei, Franca Piras, Caterina Ferreli, Maria Teresa Perra
Epithelial-mesenchymal transition (EMT) has been suggested to have a driving role in the acquisition of a metastatic potential by melanoma cells. Important hallmarks of EMT include both E-cadherin downregulation and increased expression of N-cadherin. This switch in distinct classes of adhesion molecules leads melanoma cells to lose contact with adjacent keratinocytes and interact instead with stromal fibroblasts and endothelial cells, thus promoting dermal and vascular melanoma invasion. Consequently, tumor cells migrate to distant host tissues and establish metastases...
August 21, 2017: Histochemistry and Cell Biology
Alissar El Chediak, Ali Shamseddine, Larry Bodgi, Jean-Pierre Obeid, Fady Geara, Youssef H Zeidan
Radiation therapy and immunotherapy are two highly evolving modalities for the treatment of solid tumors. Immunotherapeutic drugs can either stimulate the immune system via immunogenic pathways or target co-inhibitory checkpoints. An augmented tumor cell recognition by host immune cells can be achieved post-irradiation, as irradiated tissues can release chemical signals which are sensed by the immune system resulting in its activation. Different strategies combining both treatment modalities were tested in order to achieve a better therapeutic response and longer tumor control...
August 21, 2017: Medical Oncology
Cirous Dehghani, Sangeetha Srinivasan, Katie Edwards, Nicola Pritchard, Anthony W Russell, Rayaz A Malik, Nathan Efron
Purpose: Reduced retinal nerve fiber layer (RNFL) thickness has been demonstrated in patients with diabetic peripheral neuropathy (DPN) in cross-sectional studies. This prospective study defines longitudinal alterations to the RNFL thickness in individuals with type 1 diabetes without (DPN-ve) and with (DPN+ve) DPN and in relation to risk factors for nerve damage. Methods: A cohort of 105 individuals with type 1 diabetes (20% DPN+ve) with predominantly mild or no retinopathy and no previous retinal photocoagulation underwent spectral-domain optical coherence tomography (SD-OCT) at baseline, 2 years, and 4 years...
May 1, 2017: Investigative Ophthalmology & Visual Science
Davide Sattin, Laura Morganti, Laura De Torres, Giuliano Dolce, Francesco Arcuri, Anna Estraneo, Viviana Cardinale, Roberto Piperno, Elena Zavatta, Rita Formisano, Mariagrazia D'Ippolito, Claudio Vassallo, Barbara Dessi, Gianfranco Lamberti, Elena Antoniono, Crocifissa Lanzillotti, Jorge Navarro, Placido Bramanti, Francesco Corallo, Mauro Zampolini, Federico Scarponi, Renato Avesani, Luca Salvi, Salvatore Ferro, Luigi Mazza, Paolo Fogar, Sandro Feller, Fulvio De Nigris, Andrea Martinuzzi, Mara Buffoni, Adriano Pessina, Paolo Corsico, Matilde Leonardi
OBJECTIVE: Patients with Disorders of consciousness, are persons with extremely low functioning levels and represent a challenge for health care systems due to their high needs of facilitating environmental factors. Despite a common Italian health care pathway for these patients, no studies have analyzed information on how each region have implemented it in its welfare system correlating data with patients' clinical outcomes. MATERIALS AND METHODS: A multicenter observational pilot study was realized...
August 2017: Brain and Behavior
Rachel L Edwards, Robert C Brothers, Xu Wang, Maxim I Maron, Peter D Ziniel, Patricia S Tsang, Thomas E Kraft, Paul W Hruz, Kim C Williamson, Cynthia S Dowd, Audrey R Odom John
The emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme...
August 21, 2017: Scientific Reports
Abu Musa Md Talimur Reza, Yun-Jung Choi, Yu-Guo Yuan, Joydeep Das, Hideyo Yasuda, Jin-Hoi Kim
Many diseases, including myocardial infarction, autoimmune disease, viral diseases, neurodegenerative diseases, and cancers, are frequently diagnosed with aberrant expression of microRNAs (miRNAs) and their allied pathways. This indicates the crucial role of miRNAs in maintaining biological and physiological processes. miR-7641 is a miRNA whose role in disease has not been fully investigated. In the present study, we investigated the expression pattern of miR-7641 and its target genes in different cancer cells, as well as in clinical cancer patients...
August 21, 2017: Scientific Reports
Haipeng Liu, Danmei Su, Jinlong Zhang, Shuaishuai Ge, Youwei Li, Fei Wang, Michel Gravel, Anne Roulston, Qin Song, Wei Xu, Joshua G Liang, Gordon Shore, Xiaodong Wang, Peng Liang
TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) has long been considered a tantalizing target for cancer therapy because it mediates activation of the extrinsic apoptosis pathway in a tumor-specific manner by binding to and trimerizing its functional receptors DR4 or DR5. Despite initial promise, both recombinant human TRAIL (native TRAIL) and dimeric DR4/DR5 agonist monoclonal antibodies (mAbs) failed in multiple human clinical trials. Here we show that in-frame fusion of human C-propeptide of α1(I) collagen (Trimer-Tag) to the C-terminus of mature human TRAIL leads to a disulfide bond-linked homotrimer which can be expressed at high levels as a secreted protein from CHO cells...
August 21, 2017: Scientific Reports
Hafiz I Hussain, Zahid Iqbal, Mohamed N Seleem, Deyu Huang, Adeel Sattar, Haihong Hao, Zonghui Yuan
Numerous studies have examined the prevalence of pathogenic Escherichia coli in poultry and poultry products; however, limited data are available regarding their resistance- and virulence-associated gene expression profiles. This study was designed to examine the resistance and virulence of poultry E. coli strains in vitro and in vivo via antibiotic susceptibility, biofilm formation and adhesion, and invasion and intracellular survivability assays in Caco-2 and Raw 264.7 cell lines as well as the determination of the median lethal dose in two-day old chickens...
August 21, 2017: Scientific Reports
E Taskesen, A Mishra, S van der Sluis, R Ferrari, J H Veldink, M A van Es, A B Smit, D Posthuma, Y Pijnenburg
Frontotemporal dementia (FTD) is a neurodegenerative disorder predominantly affecting the frontal and temporal lobes. Genome-wide association studies (GWAS) on FTD identified only a few risk loci. One of the possible explanations is that FTD is clinically, pathologically, and genetically heterogeneous. An important open question is to what extent epigenetic factors contribute to FTD and whether these factors vary between FTD clinical subgroup. We compared the DNA-methylation levels of FTD cases (n = 128), and of FTD cases with Amyotrophic Lateral Sclerosis (FTD-ALS; n = 7) to those of unaffected controls (n = 193), which resulted in 14 and 224 candidate genes, respectively...
August 21, 2017: Scientific Reports
Yuki Katayama, Takuya Azechi, Motoyasu Miyazaki, Tohru Takata, Miwa Sekine, Hidehito Matsui, Hideaki Hanaki, Koji Yahara, Hiroshi Sasano, Kota Asakura, Tomoiku Takaku, Tomonori Ochiai, Norio Komatsu, Henry F Chambers
We have previsously reported a novel phenotype of vancomycin-intermediate Staphylococcus aureus (VISA) strains, "slow-VISA," in which colonies appear only after 72 h of incubation. Slow-VISA strains can be difficult to detect because prolonged incubation is required and the phenotype is unstable. To develop a method for detection of slow-VISA isolates, we studied 23 slow-VISA isolates derived from heteroVISA clinical strain Mu3. We identified single nucleotide polymorphisms (SNP) in genes involved in various pathways such as purine/pyrimidine synthesis, cell metabolism, and cell-wall peptidoglycan synthesis, which have been implicated in the stringent response...
August 21, 2017: Antimicrobial Agents and Chemotherapy
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