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https://www.readbyqxmd.com/read/29691812/excipient-selection-and-aerodynamic-characterization-of-nebulized-lipid-based-nanoemulsion-loaded-with-docetaxel-for-lung-cancer-treatment
#1
Azren Aida Asmawi, Norazlinaliza Salim, Cheng Loong Ngan, Haslina Ahmad, Emilia Abdulmalek, Mas Jaffri Masarudin, Mohd Basyaruddin Abdul Rahman
Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted...
April 24, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29691806/phosphoproteome-profiling-revealed-abnormally-phosphorylated-ampk-and-atf2-involved-in-glucose-metabolism-and-tumorigenesis-of-gh-pas
#2
S Zhao, J Feng, C Li, H Gao, P Lv, J Li, Q Liu, Y He, H Wang, L Gong, D Li, Y Zhang
PURPOSE: Protein phosphorylation plays a key role in tumorigenesis and progression. However, little is known about the phosphoproteome profiles of growth hormone-secreting pituitary adenomas (GH-PAs). The aim of this study was to identify critical biomarkers and signaling pathways that might play important roles in GH-PAs and may, therefore, represent potential therapeutic targets. METHODS: The differential phosphoprotein expression patterns involved in GH-PAs were investigated by nano-LC-MS/MS in a group of samples...
April 24, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29691732/impact-of-the-cyp3a5-1-allele-on-the-pharmacokinetics-of-tacrolimus-in-japanese-heart-transplant-patients
#3
Takaya Uno, Kyoichi Wada, Sachi Matsuda, Yuka Terada, Akira Oita, Atsushi Kawase, Mitsutaka Takada
BACKGROUND AND OBJECTIVE: Tacrolimus, a major immunosuppressant used after transplantation, is associated with large interindividual variation involving genetic polymorphisms in metabolic processes. A common variant of the cytochrome P450 (CYP) 3A5 gene, CYP3A5*3, affects blood concentrations of tacrolimus. However, tacrolimus pharmacokinetics at the early stage of transplantation have not been adequately studied in heart transplantation. We retrospectively examined the impact of the CYP3A5 genotype on tacrolimus pharmacokinetics at the early stage of heart transplantation...
April 24, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29691631/lovastatin-synergizes-with-itraconazole-against-planktonic-cells-and-biofilms-of-candida-albicans-through-the-regulation-on-ergosterol-biosynthesis-pathway
#4
Yujie Zhou, Hong Yang, Xuedong Zhou, Hongke Luo, Fan Tang, Jin Yang, Gil Alterovitz, Lei Cheng, Biao Ren
The increase of fungal infectious diseases and lack of safe and efficacious antifungal drugs result in the urgent need of new therapeutic strategies. Here, we repurposed the lovastatin (LOV) as a synergistic antifungal potentiator to itraconazole (ITZ) against Candida albicans planktonic cells and biofilms in vitro for the first time. Mutants from ergosterol biosynthesis pathway were employed and key gene expression profiles of ergosterol pathway were also measured. LOV single treatment was unable to inhibit C...
April 25, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29691579/-angiotensin-ii-promotes-the-expression-of-txnip-through-angiotensin-ii-type-1-receptor-in-islet-%C3%AE-cells
#5
Yan-Jin Feng, Jin Wang, Zhu-Jie Cao, Dan Li, Hai-Yan Huo, Xu-Mei Zhang, Xiang-Ying Jiao
This study investigated the effect of angiotensin II (Ang II) on apoptosis and thioredoxin-interacting protein (TXNIP) expression in INS-1 islet cells and the underlying mechanism. INS-1 cells cultured in vitro were treated with different concentration of Ang II for different time, and the viability was measured using cell counting kit-8 (CCK-8). After treatment with 1 × 10-6 mol/L Ang II for 24 h, flow cytometry and Western blot were used to measure the cell apoptosis, and Western blot was used to analyze the protein expression of TXNIP, carbohydrate response element-binding protein (ChREBP) and angiotensin II type 1 receptor (AT1R)...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29691471/baricitinib-induced-blockade-of-interferon-gamma-receptor-and-interleukin-6-receptor-for-the-prevention-and-treatment-of-graft-versus-host-disease
#6
Jaebok Choi, Matthew L Cooper, Karl Staser, Kidist Ashami, Kiran R Vij, Bing Wang, Lynne Marsala, Jessica Niswonger, Julie Ritchey, Bader Alahmari, Samuel Achilefu, Ikuo Tsunoda, Mark A Schroeder, John F DiPersio
The therapeutic benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are derived from the graft-versus-leukemia (GvL) effects of the procedure. There is a strong association between the GvL effects and graft-versus-host disease (GvHD), a major life-threatening complication of allo-HSCT. The limiting of GvHD while maintaining the GvL effect remains the goal of allo-HSCT. Therefore, identifying optimal therapeutic targets to selectively suppress GvHD while maintaining the GvL effects represents a significant unmet medical need...
April 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29691439/reversal-of-memory-and-neuropsychiatric-symptoms-and-reduced-tau-pathology-by-selenium-in-3xtg-ad-mice
#7
Ann Van der Jeugd, Arnaldo Parra-Damas, Raquel Baeta-Corral, Carlos M Soto-Faguás, Tariq Ahmed, Frank M LaFerla, Lydia Giménez-Llort, Rudi D'Hooge, Carlos A Saura
Accumulation of amyloid-β plaques and tau contribute to the pathogenesis of Alzheimer's disease (AD), but it is unclear whether targeting tau pathology by antioxidants independently of amyloid-β causes beneficial effects on memory and neuropsychiatric symptoms. Selenium, an essential antioxidant element reduced in the aging brain, prevents development of neuropathology in AD transgenic mice at early disease stages. The therapeutic potential of selenium for ameliorating or reversing neuropsychiatric and cognitive behavioral symptoms at late AD stages is largely unknown...
April 24, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29691406/feed-forward-alpha-particle-radiotherapy-ablates-androgen-receptor-addicted-prostate-cancer
#8
Michael R McDevitt, Daniel L J Thorek, Takeshi Hashimoto, Tatsuo Gondo, Darren R Veach, Sai Kiran Sharma, Teja Muralidhar Kalidindi, Diane S Abou, Philip A Watson, Bradley J Beattie, Oskar Vilhemsson Timmermand, Sven-Erik Strand, Jason S Lewis, Peter T Scardino, Howard I Scher, Hans Lilja, Steven M Larson, David Ulmert
Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691399/a-serum-microrna-signature-predicts-trastuzumab-benefit-in-her2-positive-metastatic-breast-cancer-patients
#9
Huiping Li, Jiang Liu, Jianing Chen, Huiyun Wang, Linbin Yang, Fei Chen, Siting Fan, Jing Wang, Bin Shao, Dong Yin, Musheng Zeng, Mengfeng Li, Jun Li, Fengxi Su, Qiang Liu, Herui Yao, Shicheng Su, Erwei Song
Trastuzumab is a standard treatment for HER2-positive (HER2+ ) breast cancer, but some patients are refractory to the therapy. MicroRNAs (miRNAs) have been used to predict therapeutic effects for various cancers, but whether miRNAs can serve as biomarkers for HER2+ metastatic breast cancer (MBC) patients remains unclear. Using miRNA microarray, we identify 13 differentially expressed miRNAs in the serum of HER2+ MBC patients with distinct response to trastuzumab, and four miRNAs are selected to construct a signature to predict survival using LASSO model...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691398/galectin-3-deficiency-drives-lupus-like-disease-by-promoting-spontaneous-germinal-centers-formation-via-ifn-%C3%AE
#10
Cristian Gabriel Beccaria, María Carolina Amezcua Vesely, Facundo Fiocca Vernengo, Ricardo Carlos Gehrau, María Cecilia Ramello, Jimena Tosello Boari, Melisa Gorosito Serrán, Juan Mucci, Eliane Piaggio, Oscar Campetella, Eva Virginia Acosta Rodríguez, Carolina Lucía Montes, Adriana Gruppi
Germinal centers (GC) are important sites for high-affinity and long-lived antibody induction. Tight regulation of GC responses is critical for maintaining self-tolerance. Here, we show that Galectin-3 (Gal-3) is involved in GC development. Compared with WT mice, Gal-3 KO mice have more GC B cells and T follicular helper cells, increased percentages of antibody-secreting cells and higher concentrations of immunoglobulins and IFN-γ in serum, and develop a lupus-like disease. IFN-γ blockade in Gal-3 KO mice reduces spontaneous GC formation, class-switch recombination, autoantibody production and renal pathology, demonstrating that IFN-γ overproduction sustains autoimmunity...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691367/upregulation-of-sall4-by-egfr-activation-regulates-the-stemness-of-cd44-positive-lung-cancer
#11
Wenjing Du, Lan Ni, Baojun Liu, Ying Wei, Yubao Lv, Sujing Qiang, Jingcheng Dong, Xijun Liu
The transcriptional factor SALL4, an important stem cell regulator, is expressed in hematopoietic stem cells and various malignancies, but its role in EGFR-mutated NSCLCs has not been studied yet. Here, we report that the expression of Sal-like protein 4 (SALL4), was significantly higher in EGFR mutated lung tumors than in non-tumor tissue. SALL4-high lung cancer patients had poorer prognosis after surgery than SALL4-low patients. The expression of SALL4 could be induced by the activation of EGFR through the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway...
April 25, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29691366/mutual-inhibition-between-hdac9-and-mir-17-regulates-osteogenesis-of-human-periodontal-ligament-stem-cells-in-inflammatory-conditions
#12
Liya Li, Wenjia Liu, Hong Wang, Qianjuan Yang, Liqiang Zhang, Fang Jin, Yan Jin
Histone deacetylases (HDAC) plays important roles in the post-translational modifications of histone cores as well as non-histone targets. Many of them are involved in key inflammatory processes. Despite their importance, whether and how HDAC9 is regulated under inflammatory conditions remains unclear. The aim of this study was to evaluate the effects of HDAC9 under chronic inflammation condition in human periodontal ligament stromal cell (PDLSCs) and to explore the underlying regulatory mechanism. PDLSCs from healthy or periodontitis human tissue was compared...
April 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29691318/control-of-motor-coordination-by-astrocytic-tonic-gaba-release-through-modulation-of-excitation-inhibition-balance-in-cerebellum
#13
Junsung Woo, Joo Ok Min, Dae-Si Kang, Yoo Sung Kim, Guk Hwa Jung, Hyun Jung Park, Sunpil Kim, Heeyoung An, Jea Known, Jeongyeon Kim, Insop Shim, Hyung-Gun Kim, C Justin Lee, Bo-Eun Yoon
Tonic inhibition in the brain is mediated through an activation of extrasynaptic GABAA receptors by the tonically released GABA, resulting in a persistent GABAergic inhibitory action. It is one of the key regulators for neuronal excitability, exerting a powerful action on excitation/inhibition balance. We have previously reported that astrocytic GABA, synthesized by monoamine oxidase B (MAOB), mediates tonic inhibition via GABA-permeable bestrophin 1 (Best1) channel in the cerebellum. However, the role of astrocytic GABA in regulating neuronal excitability, synaptic transmission, and cerebellar brain function has remained elusive...
April 24, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29691303/therapy-of-endocrine-disease-denosumab-versus-bisphosphonates-for-the-treatment-of-postmenopausal-osteoporosis
#14
Athanasios D Anastasilakis, Stergios A Polyzos, Polyzois Makras
The most widely used medications for the treatment of osteoporosis are currently bisphosphonates and denosumab. Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Denosumab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pre-treated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, bisphosphonates reach a plateau in BMD response after 2-3 years, especially at the hip, while BMD increases progressively for as long as denosumab is administered...
April 24, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29691298/enhanced-therapeutic-activity-of-non-internalizing-small-molecule-drug-conjugates-targeting-carbonic-anhydrase-ix-in-combination-with-targeted-interleukin-2
#15
Samuele Cazzamalli, Barbara Ziffels, Fontaine Widmayer, Patrizia Murer, Giovanni Pellegrini, Francesca Pretto, Sarah Wulhfard, Dario Neri
PURPOSE: Antibody-drug conjugates and small molecule-drug conjugates have been proposed as alternatives to conventional anti-cancer cytotoxic agents, with the potential to deliver bioactive payloads to the site of disease, helping spare normal tissues. Experimental Design: Here we describe a novel small molecule-drug conjugate, based on a high-affinity ligand specific to carbonic anhydrase IX. The product featured a peptidic linker, suitable for cleavage in the tumor extracellular environment, and monomethyl auristatin E as cytotoxic payload...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691296/tryptophan-metabolism-contributes-to-radiation-induced-immune-checkpoint-reactivation-in-glioblastoma
#16
Pravin Kesarwani, Antony Prabhu, Shiva Kant, Praveen Kumar, Stewart F Graham, Katie L Buelow, George D Wilson, Christopher Ryan Miller, Prakash Chinnaiyan
PURPOSE: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).  Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691292/phenformin-induced-mitochondrial-dysfunction-sensitizes-hepatocellular-carcinoma-for-dual-inhibition-of-mtor
#17
Sonia Rosa Veiga, Xuemei Ge, Carol A Mercer, María Isabel Hernández-Alvarez, Hala Elnakat Thomas, Javier Hernández-Losa, Santiago Ramón Y Cajal, Antonio Zorzano, George Thomas, Sara C Kozma
PURPOSE: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29691282/the-compound-millepachine-and-its-derivatives-inhibit-tubulin-polymerization-by-irreversibly-binding-to-the-colchicine-binding-site-in-%C3%AE-tubulin
#18
Yang Jianhong, Yan Wei, Yu Yamei, Wang Yuxi, Yang Tao, Xue Linlin, Yuan Xue, Long Caofeng, Liu Zuowei, Chen Xiaoxin, Hu Mengshi, Zheng Li, Qiu Qiang, Pei Heying, Li Dan, Wang Fang, Bai Peng, Wen Jiaolin, Ye Haoyu, Chen Lijuan
Inhibitors that bind to the paclitaxel- or vinblastine-binding sites of tubulin have been part of the pharmacopoeia of anticancer therapy for decades. However, tubulin inhibitors that bind to the colchicine-binding site are not used in clinical cancer therapy, because of their low therapeutic index. To address multidrug resistance to many conventional tubulin-binding agents, numerous efforts have attempted to clinically develop inhibitors that bind the colchicine-binding site. Previously, we have found that millepachine (MIL), a natural chalcone-type small molecule extracted from the plant Millettia pachycarpa, and its two derivatives (MDs) SKLB028 and SKLB050 have potential antitumor activities both in vitro and in vivo...
April 24, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29691215/perceived-drivers-and-barriers-to-the-adoption-of-emental-health-by-psychologists-the-construction-of-the-levels-of-adoption-of-emental-health-model
#19
Milou A Feijt, Yvonne Aw de Kort, Inge Mb Bongers, Wijnand A IJsselsteijn
BACKGROUND: The internet offers major opportunities in supporting mental health care, and a variety of technology-mediated mental and behavioral health services have been developed. Yet, despite growing evidence for the effectiveness of these services, their acceptance and use in clinical practice remains low. So far, the current literature still lacks a structured insight into the experienced drivers and barriers to the adoption of electronic mental health (eMental health) from the perspective of clinical psychologists...
April 24, 2018: Journal of Medical Internet Research
https://www.readbyqxmd.com/read/29691139/development-of-piperazine-based-hydroxamic-acid-inhibitors-against-falcilysin-an-essential-malarial-protease
#20
Jeffrey P Chance, Hannah Fejzic, Obiel Hernandez, Eva S Istvan, Armann Andaya, Nikolay Maslov, Ruby Aispuro, Teodulo Crisanto, Huyen Nguyen, Brian Vidal, Whitney Serrano, Bradley Kuwahara, Corey Pugne Andanado, Daniel E Goldberg, Jeremy P Mallari
The human parasite Plasmodium falciparum kills an estimated 445,000 people a year, with the most fatalities occurring in African children. Previous studies identified falcilysin (FLN) as a malarial metalloprotease essential for parasite development in the human host. Despite its essentiality, the biological roles of this protease are not well understood. Here we describe the optimization of a piperazine-based hydroxamic acid scaffold to develop the first reported inhibitors of FLN. Inhibitors were tested against cultured parasites, and parasiticidal activity correlated with potency against FLN...
April 19, 2018: Bioorganic & Medicinal Chemistry Letters
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