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drug target disease

Sven Rutkowski, Ling Mu, Tieyan Si, Meiyu Gai, Mengmeng Sun, Johannes Frueh, Qiang He
One of the most promising future applications of hydrogels is drug delivery. The hydrogels act as a biomedical cargo model to reach the target and release drugs to cure diseases. This application requires no side effects of the hydrogel and the ability to pass through porous media (e.g. membranes, interstitial tissue etc.) with nanoscaled channels. At the same time, the hydrogel must be mass-producible in an economic way. In this work, we show that hydrodynamic electrospray ionization jetting combined with ultrasound can fulfill these high requirements...
November 28, 2018: Colloids and Surfaces. B, Biointerfaces
Hugh C Welles, Madeleine F Jennewein, Rosemarie D Mason, Sandeep Narpala, Lingshu Wang, Cheng Cheng, Yi Zhang, John-Paul Todd, Jeffrey D Lifson, Alejandro B Balazs, Galit Alter, Adrian B McDermott, John R Mascola, Mario Roederer
Gene based delivery of immunoglobulins promises to safely and durably provide protective immunity to individuals at risk of acquiring infectious diseases such as HIV. We used a rhesus macaque animal model to optimize delivery of naturally-arising, autologous anti-SIV neutralizing antibodies expressed by Adeno-Associated Virus 8 (AAV8) vectors. Vectored transgene expression was confirmed by quantitation of target antibody abundance in serum and mucosal surfaces. We tested the expression achieved at varying doses and numbers of injections...
December 5, 2018: PLoS Pathogens
Indu Warrier, Nikhil Ram-Mohan, Zeyu Zhu, Ariana Hazery, Haley Echlin, Jason Rosch, Michelle M Meyer, Tim van Opijnen
Efficient and highly organized regulation of transcription is fundamental to an organism's ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their regulation is crucial to determining how pathogenic bacteria cause disease and how they may be inhibited. In this study, we map the transcriptional landscape of the bacterial pathogen Streptococcus pneumoniae TIGR4 by applying a combination of high-throughput RNA-sequencing techniques...
December 5, 2018: PLoS Pathogens
Ali Çoner, Davran Çiçek, Sinan Akıncı, Serhat Balcıoğlu, Cihan Altın, Haldun Müderrisoğlu
OBJECTIVE: Diffuse coronary artery disease (CAD) is a challenging issue in clinical cardiology practice. There are limited data about percutaneous revascularization in these patients. METHODS: This study was an observational clinical evaluation. The records of patients with diffuse CAD revascularized with new-generation drug-eluting stents (DES) were researched retrospectively. Patients treated with multiple, overlapping new-generation DES (at least 60mm in length per vessel) were included...
December 2018: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
Congshan Liu, Jiaqing Yao, Jianhai Yin, Jian Xue, Haobing Zhang
Echinococcosis, which causes a high disease burden and is of great public health significance, is caused by the larval stage of Echinococcus species. It has been suggested that tubulin is the target of benzimidazoles, the only drugs for the treatment of echinococcosis. This study evaluated the characteristics of tubulins from Echinococcus granulosus. The full-length cDNAs of E. granulosus α- and β-tubulin isoforms were cloned by reverse transcription PCR from protoscolex RNA. Then, these two tubulin isoforms (α9 and β4 ) were recombinantly expressed as insoluble inclusion bodies in Escherichia coli...
2018: Parasite: Journal de la Société Française de Parasitologie
Gunter von Minckwitz, Chiun-Sheng Huang, Max S Mano, Sibylle Loibl, Eleftherios P Mamounas, Michael Untch, Norman Wolmark, Priya Rastogi, Andreas Schneeweiss, Andres Redondo, Hans H Fischer, William Jacot, Alison K Conlin, Claudia Arce-Salinas, Irene L Wapnir, Christian Jackisch, Michael P DiGiovanna, Peter A Fasching, John P Crown, Pia Wülfing, Zhimin Shao, Elena Rota Caremoli, Haiyan Wu, Lisa H Lam, David Tesarowski, Melanie Smitt, Hannah Douthwaite, Stina M Singel, Charles E Geyer
BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy...
December 5, 2018: New England Journal of Medicine
Elena K Schneider-Futschik, Daniel Hoyer, Alex Khromykh, Jonathan B Baell, Glenn Marsh, Mark A Baker, Jian Li, Tony Velkov
The Ebola virus has a grave potential to destabilise civil society as we know it. The past few deadly Ebola outbreaks were unprecedented in size: the virus spread from the epicentres of Guinea, Sierra Leone, Nigeria and Liberia. The 2014-15 Ebola West Africa outbreak was associated with almost 30,000 suspected or confirmed cases and over 11,000 documented deaths. There is a general acceptance within the World Health Organisation (WHO) and the Ebola outbreak response community that future outbreaks will become increasingly more frequent and more likely to involve inter-continental transmission...
December 5, 2018: ACS Infectious Diseases
Shadi Rabiee, Shima Tavakol, Mahmoud Barati, Mohammad Taghi Joghataei
Cancer as a multifactorial and smart disease is now considered a challenging problem. Despite many investigations on drug discovery, it remains incurable, in part, due to insufficient understanding of its special mechanisms. For the first time, we collaterally investigated the effect of acidosis on the contribution of apoptosis, necrosis, and autophagy in MDA-MB 231 cells. Our data showed that necrosis, apoptosis, and intracellular reactive oxygen species production drastically decreased from 48 to 72 hr while cell viability and autophagy increased along with a gap between the percentages...
December 4, 2018: Journal of Cellular Physiology
Xiaoying Lian, Xiaoyuan Wu, Zhongxin Li, Yingjie Zhang, Kangkang Song, Guangyan Cai, Qinggang Li, Shupeng Lin, Xiangmei Chen, Xue-Yuan Bai
BACKGROUND AND PURPOSE: The pathogenic mechanism of autosomal dominant polycystic kidney disease (ADPKD) is unclear. Similar to tumor cells, polycystic kidney cells are primarily dependent on aerobic glycolysis for ATP production. Compared with rodents, miniature pigs are more similar to humans. This study is the first time to investigate the effects of the combination of metformin and 2DG in a chronic progressive ADPKD miniature pig model. EXPERIMENTAL APPROACH: A miniature pig ADPKD model was established by inducible deletion of the PKD1 gene...
December 4, 2018: British Journal of Pharmacology
Marilyn J Telen, Punam Malik, Gregory M Vercellotti
For over 100 years, clinicians and scientists have been unravelling the consequences of the A to T substitution in the β-globin gene that produces haemoglobin S, which leads to the systemic manifestations of sickle cell disease (SCD), including vaso-occlusion, anaemia, haemolysis, organ injury and pain. However, despite growing understanding of the mechanisms of haemoglobin S polymerization and its effects on red blood cells, only two therapies for SCD - hydroxyurea and L-glutamine - are approved by the US Food and Drug Administration...
December 4, 2018: Nature Reviews. Drug Discovery
Michael Bartoschek, Nikolay Oskolkov, Matteo Bocci, John Lövrot, Christer Larsson, Mikael Sommarin, Chris D Madsen, David Lindgren, Gyula Pekar, Göran Karlsson, Markus Ringnér, Jonas Bergh, Åsa Björklund, Kristian Pietras
Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium...
December 4, 2018: Nature Communications
Xuan Li, Jia Liu, Qingguo Lu, Di Ren, Xiaodong Sun, Thomas Rousselle, Yi Tan, Ji Li
Heart failure (HF) is a serious disease with high mortality. The incidence of this disease has continued to increase over the past decade. All cardiovascular diseases causing dysfunction of various physiological processes can result in HF. AMP-activated protein kinase (AMPK), an energy sensor, has pleiotropic cardioprotective effects and plays a critical role in the progression of HF. In this review, we highlight that AMPK can not only improve the energy supply in the failing heart by promoting ATP production, but can also regulate several important physiological processes to restore heart function...
December 4, 2018: Bioscience Reports
Krishnaveni Mohareer, Suman Asalla, Sharmistha Banerjee
Tuberculosis (TB) continues to be the leading cause of death by any single infectious agent, accounting for around 1.7 million annual deaths globally, despite several interventions and support programs by national and international agencies. With the development of drug resistance in Mycobacterium tuberculosis (M. tb), there has been a paradigm shift in TB research towards host-directed therapy. The potential targets include the interactions between host and bacterial proteins that are crucial for pathogenesis...
December 2018: Tuberculosis
Fatima Karzai, David VanderWeele, Ravi A Madan, Helen Owens, Lisa M Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L Beshiri, Kathleen Kelly, Venkatesh Krishnasamy, Sunmin Lee, Min-Jung Lee, Akira Yuno, Jane B Trepel, Maria J Merino, Ryan Dittamore, Jennifer Marté, Renee N Donahue, Jeffrey Schlom, Keith J Killian, Paul S Meltzer, Seth M Steinberg, James L Gulley, Jung-Min Lee, William L Dahut
BACKGROUND: Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC)...
December 4, 2018: Journal for Immunotherapy of Cancer
Jiantao Sun, Jiemei Yang, Jing Chi, Xue Ding, Nan Lv
BACKGROUND: Cardiac hypertrophy and acute myocardial infarction (AMI) are two common heart diseases worldwide. However, research is needed into the exact pathogenesis and effective treatment strategies for these diseases. Recently, microRNAs (miRNAs) have been suggested to regulate the pathological pathways of heart disease, indicating a potential role in novel treatments. RESULTS: In our study, we constructed a miRNA-gene-drug network and analyzed its topological features...
December 4, 2018: Human Genomics
Yanli Wang, Yanling Wang, Ran Sun, Xingrao Wu, Xu Chu, Shuhu Zhou, Xibin Hu, Lingyun Gao, Qingxia Kong
BACKGROUND: Temporal lobe epilepsy (TLE) is a common and often refractory brain disease that is closely correlated with inflammation. Alpha-methyl-L-tryptophan (AMT) is recognized as a surrogate marker for epilepsy, characterized by high uptake in the epileptic focus. There are many advantages of using the magnetic targeting drug delivery system of superparamagnetic iron oxide nanoparticles (SPIONs) to treat many diseases, including epilepsy. We hypothesized that AMT and an IL-1β monoclonal antibody (anti-IL-1β mAb) chelated to SPIONs would utilize the unique advantages of SPIONs and AMT to deliver the anti-IL-1β mAb across the blood-brain barrier (BBB) as a targeted therapy...
December 4, 2018: Journal of Translational Medicine
Tajudeen O Yahaya, Titilola F Salisu
INTRODUCTION: Scientists are considering the possibility of treating diabetes mellitus (DM) using a personalized approach in which various forms of the diseases will be treated based on the causal gene and its pathogenesis. To this end, scientists have identified mutations in certain genes as probable causes of Type 2 diabetes mellitus (T2DM) with diverse mechanisms. AIM: This review was aimed at articulating already identified T2DM genes with their mechanisms of action and phenotypic presentations for the awareness of all stakeholders...
December 4, 2018: Current Diabetes Reviews
C Antza, I Doundoulakis, M Natsis, V Kotsis
Artery disease can be identified from ankle-brachial index (peripheral artery disease), pulse wave velocity (arterial stiffness), carotid intima media thickness (atherosclerosis) and flow-mediated dilation (endothelial disfunction). Arterial stiffness is a marker of cardiovascular disease associated with cardiovascular events. Increased vascular ageing is the acceleration of arterial stiffness inappropriate for the given chronological age. Treatment of early vascular ageing seems to be important if we target on primary cardiovascular prevention...
December 4, 2018: Current Pharmaceutical Design
Seiji Kakiuchi, Kimikazu Yakushijin, Rina Sakai, Koji Kawaguchi, Ako Higashime, Keiji Kurata, Hiroya Ichikawa, Shigeki Nagao, Junpei Rikitake, Naomi Kiyota, Hiroshi Matsuoka, Hironobu Minami
A 69-year-old woman who had been diagnosed with unresectable papillary thyroid cancer was referred to our hospital. We initially treated her with sorafenib, but she subsequently developed erythema multiforme, which was suspected to be a drug rush due to sorafenib; therefore, sorafenib was discontinued. At the time of discontinuation, immature blast cells were detected in her peripheral blood. Approximately two weeks later, her skin rash improved substantially, but the proportion of blasts in the peripheral blood increased...
December 4, 2018: Journal of Oncology Pharmacy Practice
Nannan Sun, Congmin Yuan, Xiaojun Ma, Yonghui Wang, Xianfeng Gu, Wei Fu
As an attractive drug-target, retinoic acid receptor-related orphan receptor-gamma-t (RORγt) has been employed widely to develop clinically relevant small molecular modulators as potent therapy for autoimmune disease and cancer, but its molecular mechanism of action (MOA) remains unclear. In the present study, we designed and discovered two novel RORγt ligands that are similar in structure, but different in efficacy. Using fluorescence resonance energy transfer (FRET) assay, compound 1 was identified as an agonist with an EC50 of 3...
December 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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