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https://www.readbyqxmd.com/read/28528212/targeted-co-delivery-of-polypyrrole-and-rapamycin-by-trastuzumab-conjugated-liposomes-for-combined-chemo-photothermal-therapy
#1
Hanh Thuy Nguyen, Tuan Hiep Tran, Raj Kumar Thapa, Cao Dai Phung, Beom Soo Shin, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Trastuzumab is a therapeutic monoclonal antibody that selectively recognizes HER2/neu receptor for targeting breast cancers. In this study, we aimed to present a strategy to combine chemo and phototherapy and targeted delivery via monoclonal antibody for enhanced anticancer effects. We co-loaded a chemotherapeutic agent, rapamycin, and a photosensitizer, polypyrrole, in trastuzumab-conjugated liposomes (LRPmAb) for combined chemo-photothermal therapy. LRPmAb had small size (172.2±9.6nm), narrow distribution, and negative ζ-potential (-12...
May 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28527722/crispr-cas9-mediated-ccr5-ablation-in-human-hematopoietic-stem-progenitor-cells-confers-hiv-1-resistance-in%C3%A2-vivo
#2
Lei Xu, Huan Yang, Yang Gao, Zeyu Chen, Liangfu Xie, Yulin Liu, Ying Liu, Xiaobao Wang, Hanwei Li, Weifeng Lai, Yuan He, Anzhi Yao, Liying Ma, Yiming Shao, Bin Zhang, Chengyan Wang, Hu Chen, Hongkui Deng
Transplantation of hematopoietic stem cells (HSCs) with a naturally occurring CCR5 mutation confers a loss of detectable HIV-1 in the patient, making ablation of the CCR5 gene in HSCs an ideal therapy for an HIV-1 cure. Although CCR5 disruption has been attempted in CD4(+) T cells and hematopoietic stem/progenitor cells (HSPCs), efficient gene editing with high specificity and long-term therapeutic potential remains a major challenge for clinical translation. Here, we established a CRISPR/Cas9 gene editing system in human CD34(+) HSPCs and achieved efficient CCR5 ablation evaluated in long-term reconstituted NOD/Prkdc(scid)/IL-2Rγ(null) mice...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28527670/vulvar-fibroepithelial-polyps-in-an-adolescent-female
#3
Jonathan Avila, Kathleen Nicol, Steven C Matson
BACKGROUND: Fibroepithelial polyps (FEPs) are benign tumors, of possibly hormone-dependent nature, found in the vulvovaginal region of women of reproductive age. CASE: A 15-year-old adolescent girl, on hormonal contraceptive therapy, who presented with multiple vulvar masses with histopathology consistent with FEP. SUMMARY AND CONCLUSION: The spectrum of the morphology of FEPs may make their diagnosis challenging. We describe a rare presentation of vulvar fibroepithelial polyps in an adolescent girl on hormonal contraceptive therapy...
May 17, 2017: Journal of Pediatric and Adolescent Gynecology
https://www.readbyqxmd.com/read/28527126/polycaprolactone-based-nanoparticles-loaded-with-indomethacin-for-anti-inflammatory-therapy-from-preparation-to-ex-vivo-study
#4
Waisudin Badri, Karim Miladi, Sophie Robin, Céline Viennet, Qand Agha Nazari, Géraldine Agusti, Hatem Fessi, Abdelhamid Elaissari
PURPOSE: This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration...
May 19, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28526928/exosomes-in-cardiovascular-medicine
#5
REVIEW
Iain M Dykes
Exosomes are small, extracellular membrane-bound particles that mediate intercellular transport of a cytosolic cargo. Exosomal transfer of micro-RNA can modify gene expression in targeted cells. Exosome-based endocrine/paracrine signaling has been shown to be involved in a wide range of physiological processes including those associated with cardiovascular injury and disease, but remains relatively poorly understood. Exosomes offer great potential to the clinical field, with applications in both diagnostics and therapeutics...
May 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28526927/sodium-thiosulphate-attenuates-brain-inflammation-induced-by-systemic-lipopolysaccharide-administration-in-c57bl-6j-mice
#6
Gonzalo Acero, Miryam Nava Catorce, Ricardo González-Mendoza, Marco Antonio Meraz-Rodríguez, Luis Fernando Hernández-Zimbron, Roberto González-Salinas, Goar Gevorkian
It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration...
May 19, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28526832/identification-of-a-novel-chalcone-derivative-that-inhibits-notch-signaling-in-t-cell-acute-lymphoblastic-leukemia
#7
Mattia Mori, Luca Tottone, Deborah Quaglio, Nadezda Zhdanovskaya, Cinzia Ingallina, Marisa Fusto, Francesca Ghirga, Giovanna Peruzzi, Maria Elisa Crestoni, Fabrizio Simeoni, Francesca Giulimondi, Claudio Talora, Bruno Botta, Isabella Screpanti, Rocco Palermo
Notch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526628/heparin-based-hydrogels-induce-human-renal-tubulogenesis-in-vitro
#8
Heather M Weber, Mikhail V Tsurkan, Valentina Magno, Uwe Freudenberg, Carsten Werner
Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy...
May 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28526416/treatment-strategy-for-type-2-diabetes-with-obesity-focus-on-glucagon-like-peptide-1-receptor-agonists
#9
REVIEW
Qiuhe Ji
PURPOSE: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain...
May 16, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28525856/oleuropein-prevents-the-development-of-experimental-autoimmune-myocarditis-in-rats
#10
Jia-Ying Zhang, Zheng Yang, Kun Fang, Zhan-Li Shi, Dan-Hong Ren, Jing Sun
Oleuropein (OLE) is a natural secoiridoid that is derived from Olea europaea. OLE possesses cardioprotective effects in experimental models of hypertension, myocardial infarction, atherosclerosis and hyperlipidaemia. In the present study, the effects of OLE on experimental autoimmune myocarditis (EAM) were evaluated. EAM in rats were induced by subcutaneous injections of porcine cardiac myosin. Cardiac function parameters, myocardial pathology, myocardial inflammatory cell infiltration and nuclear factor kappa-B (NF-κB) expression were measured...
May 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#11
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525374/the-effect-of-rapamycin-nvp-bez235-aspirin-and-metformin-on-pi3k-akt-mtor-signaling-pathway-of-pik3ca-related-overgrowth-spectrum-pros
#12
Yasuyo Suzuki, Yasushi Enokido, Kenichiro Yamada, Mie Inaba, Kumiko Kuwata, Naoki Hanada, Tsuyoshi Morishita, Seiji Mizuno, Nobuaki Wakamatsu
The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is critical for cellular growth and metabolism. Recently, mosaic or segmental overgrowth, a clinical condition caused by heterozygous somatic activating mutations in PIK3CA, was established as PIK3CA-related overgrowth spectrum (PROS). In this study, we report a Japanese female diagnosed with PROS, who presented with hyperplasia of the lower extremities, macrodactyly, multiple lipomatosis, and sparse hair. Sequencing and mutant allele frequency analysis of PIK3CA from affected tissues revealed that the patient had a heterozygous mosaic mutation (c...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525359/i36t%C3%A2-t-mutation-in-south-african-subtype-c-c-sa-hiv-1-protease-significantly-alters-protease-drug-interactions
#13
Sibusiso B Maseko, Eden Padayachee, Thavendran Govender, Yasien Sayed, Gert Kruger, Glenn E M Maguire, Johnson Lin
The efficacy of HIV-1 protease inhibition therapies is often compromised by the emergence of mutations in the protease molecule that reduces the binding affinity of inhibitors while maintaining viable catalytic activity and affinity for natural substrates. In the present study, we used a recombinant HIV-1 C-SA protease and a recently reported variant for inhibition (Ki, IC50) and thermodynamic studies against nine clinically used inhibitors. This is the first time that binding free energies for C-SA PR and the mutant are reported...
May 19, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28524762/exosomes-promote-restoration-after-an-experimental-animal-model-of-intracerebral-hemorrhage
#14
Laura Otero-Ortega, Mari Carmen Gómez de Frutos, Fernando Laso-García, Berta Rodríguez-Frutos, Esperanza Medina-Gutiérrez, Juan Antonio López, Jesús Vázquez, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Exosomes are gaining importance because they show great promise in therapeutic applications for several diseases. Particularly in stroke, exosomes derived from mesenchymal stem cell (MSC) therapy work as paracrine effectors responsible for promoting neurovascular remodeling and functional recovery. Adult male rats were subjected to intracerebral hemorrhage (ICH) by intrastriatal injection of collagenase type IV; 24 h after surgery, MSC-derived exosomes were administered through the tail vein. The rats were euthanized at 7 or 28 days after treatment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28524623/upper-gastrointestinal-complications-following-ablation-therapy-for-atrial-fibrillation
#15
S-Y Park, M Camilleri, D Packer, K Monahan
BACKGROUND: Following ablation therapy for cardiac arrhythmias, patients may develop upper gastrointestinal (UGI) symptoms. The vagus nerve is close to the atria and may be affected by ablating energy. AIM: To identify structural or functional complications in UGI tract following ablation for atrial fibrillation (AF) and clinical outcomes and association with vagal dysfunction. METHODS: Using natural language processing of electronic medical records and an AF ablation database of 5380 patients treated during 17 years, we identified 40 patients with UGI complications...
May 19, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28524215/-novel-therapies-in-neurometabolic-diseases-the-importance-of-early-intervention
#16
L G Gutierrez-Solana
INTRODUCTION: Individually, neurometabolic diseases are ultra rare, but for some of them there is an effective treatment. DEVELOPMENT: Several recent therapeutic advances are reviewed. Today, the possibilities of treatment for lysosomal diseases have improved. In recent years the use of enzyme replacement therapy has become more widely extended to treat mucopolysaccharidosis type IVA (Morquio A), mucopolysaccharidosis type VII (Sly syndrome), lysosomal acid lipase deficiency and alpha-mannosidosis...
May 17, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28522743/forward-to-the-past-the-case-for-quantitative-pet-imaging
#17
Adriaan A Lammertsma
Positron emission tomography (PET) was developed in the 1970's as an in vivo method to measure regional pathophysiological processes. In the 1990's the focus moved to the detection of local increases in uptake, first in the brain (activation studies) and later in oncology (finding metastases), where (18)F-FDG emerged as a highly sensitive staging technique. This focus on sensitivity has overshadowed the other main characteristic of PET, its quantitative nature. In recent years there has been a new shift. PET is now seen as a promising tool for drug development and precision medicine, i...
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28522654/diabetic-kidney-disease-challenges-progress-and-possibilities
#18
Radica Z Alicic, Michele T Rooney, Katherine R Tuttle
Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis...
May 18, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28522586/antitumor-synergism-and-enhanced-survival-with-a-tumor-vasculature-targeted-enzyme-prodrug-system-rapamycin-and-cyclophosphamide
#19
John J Krais, Needa Virani, Partick H McKernan, Quang Nguyen, Kar-Ming Fung, Vassilios I Sikavitsas, Carla D Kurkjian, Roger G Harrison
Mutant cystathionine gamma-lyase was targeted to phosphatidylserine exposed on tumor vasculature through fusion with annexin A1 or annexin A5.  Cystathionine gamma-lyase E58N, R118L, and E338N mutations impart non-native methionine gamma-lyase activity, resulting in tumor-localized generation of highly toxic methylselenol upon systemic administration of non-toxic selenomethionine.  The described therapeutic system circumvents systemic toxicity issues using a novel drug delivery/generation approach and avoids the administration of non-native proteins and/or DNA required with other enzyme prodrug systems...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522215/blocking-voltage-gated-sodium-channels-as-a-strategy-to-suppress-pathological-cough
#20
REVIEW
Hui Sun, Marian Kollarik, Bradley J Undem
Pathological cough is thought to be secondary to inappropriate activation of vagal sensory nerves. Sensory nerves can be activated by a large number of disparate stimuli. The most relevant stimuli to block for effective anti-tussive therapy likely depend on the specific underlying pathology that is leading to the coughing. Blocking voltage-gated sodium channels (NaV) will prevent action potential initiation and conduction and therefore prevent sensory communication between the airways and brainstem. In so doing, they would be expected to inhibit evoked cough independently of the nature of the stimulus and underlying pathology...
May 15, 2017: Pulmonary Pharmacology & Therapeutics
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