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https://www.readbyqxmd.com/read/29034584/modern-therapeutic-approaches-for-noninfectious-ocular-diseases-involving-inflammation
#1
REVIEW
Michelle L Ratay, Elena Bellotti, Riccardo Gottardi, Steven R Little
Dry eye disease, age-related macular degeneration, and uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, proinflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies are developed to either address the symptoms or abate the underlying cause of these diseases. Herein, the challenges to deliver drugs to the relevant location in the eye for each of these diseases are reviewed along with current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment...
October 16, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29033244/iaspp-is-an-antioxidative-factor-and-drives-cancer-growth-and-drug-resistance-by-competing-with-nrf2-for-keap1-binding
#2
Wenjie Ge, Kunming Zhao, Xingwen Wang, Huayi Li, Miao Yu, Mengmeng He, Xuting Xue, Yifu Zhu, Cheng Zhang, Yiwei Cheng, Shijian Jiang, Ying Hu
Reactive oxygen species (ROS) have emerged as important signaling molecules that play crucial roles in carcinogenesis and cytotoxic responses. Nrf2 is the master regulator of ROS balance. Thus, uncovering mechanisms of Nrf2 regulation is important for the development of alternative treatment strategies for cancers. Here, we demonstrate that iASPP, a known p53 inhibitor, lowers ROS independently of p53. Mechanistically, iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination and increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation...
October 5, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29033234/antibacterial-constituents-of-the-plant-family-amaryllidaceae
#3
REVIEW
Jerald J Nair, Anke Wilhelm, Susanna L Bonnet, Johannes van Staden
There is a pressing need in antibiotic drug discovery for new drugs to counterbalance the effects of multidrug resistance. Plants represent a viable platform for such endeavors owing to their traditional relevance in infectious disease therapies as well as their vast chemical resources. As many as fifty different species of the Amaryllidaceae are discernible with such functions in traditional medicine, thirty-nine of which have been subjected to pharmacological evaluations. Submicromolar antibacterial activities for several of these plants have been the driving force behind studies targeting their active constituents...
September 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29031973/predicting-solubility-miscibility-in-amorphous-dispersions-it-s-time-to-move-beyond-regular-solution-theories
#4
REVIEW
Bradley D Anderson
The evolving challenges associated with the development of poorly soluble drug molecules have been met with major advances in drug solubilization. In particular, amorphous solid dispersion technology is becoming an increasingly important option to enhance oral bioavailability by creating prolonged drug supersaturation to maximize the driving force for intestinal absorption. A primary concern in the development of amorphous solid dispersions is their physical stability, leading to increasing interest in predictive methodologies to assess the propensity for drug crystallization under various storage conditions...
October 11, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29030532/mechanistic-investigation-on-grinding-induced-subvisible-particle-formation-during-mixing-and-filling-of-monoclonal-antibody-formulations
#5
Benson Gikanga, Ada Hui, Yuh-Fun Maa
Processing equipment involving grinding of two solid surfaces has been demonstrated to induce subvisible particle (SvP) formation in monoclonal antibody (mAb) drug product manufacturing processes. This study elucidated potential stress types associated with grinding action to identify the stress mechanism responsible for SvP formation. Several potential stress types can be associated with the grinding action, including interfacial stresses (air-liquid and liquid-solid), hydraulic/mechanical shear stress, cavitation, nucleation of stressed protein molecules, and localized thermal stress...
October 12, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/29029317/the-critical-role-of-supply-chains-in-preventing-human-immunodeficiency-virus-drug-resistance-in-low-and-middle-income-settings
#6
Thomas Minior, Meaghan Douglas, Dianna Edgil, Meena Srivastava, John Crowley, Jacqueline Firth, Ilana Lapidos-Salaiz, Jason Williams, Lana Lee
The functioning of the supply chain may be a driving factor behind the development of human immunodeficiency virus (HIV) drug resistance (HIVDR) in many low- and middle-income countries (LMICs). Additionally, the effectiveness of supply chains will likely impact the scale-up of both viral-load monitoring and HIVDR testing. This article describes the complexities of global supply chains relevant for LMICs and presents early data on stock-outs and drug substitutions in several countries supported by the US President's Emergency Plan for AIDS Relief...
October 6, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29028572/supramolecular-gels-using-an-amide-functionalized-imidazolium-based-surfactant
#7
Ni Cheng, Qi Kang, Jianhong Xiao, Na Du, Li Yu
Studies on supramolecular gel aggregates via supramolecular interactions are very fascinating and impressive. The interactions of gelator with solvent and inorganic salt can functionalize, activate, or control the properties of supramolecular gels. A lot of work on this area has been done, but all these contributions are only at an early stage. In this work, we tuned the gel formation conditions and properties by using low-molecular-weight gelator (LMWGs), amide-functionalized imidazolium-based surfactant, viz...
October 4, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29028303/neutrophil-particle-interactions-in-blood-circulation-drive-particle-clearance-and-alter-neutrophil-responses-in-acute-inflammation
#8
Catherine A Fromen, William J Kelley, Margaret B Fish, Reheman Adili, Jeffery Noble, Mark J Hoenerhoff, Michael Holinstat, Omolola Eniola-Adefeso
Although nano- and microparticle therapeutics have been studied for a range of drug delivery applications, the presence of these particles in blood flow may have considerable and understudied consequences to circulating leukocytes, especially neutrophils, which are the largest human leukocyte population. The objective of this work was to establish if particulate drug carriers in circulation interfere with normal neutrophil adhesion and migration. Circulating blood neutrophils in vivo were found to be capable of rapidly binding and sequestering injected carboxylate-modified particles of both 2 µm and 0...
October 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/29028228/preventing-emergence-of-drug-resistant-tuberculosis-in-myanmar-s-transitioning-health-system
#9
Mishal S Khan, Coll Hutchison, Richard J Coker, Joanne Yoong, Khaung M Hane, Anh L Innes, Tin M Khaing, Sithu Aung
Multidrug-resistant tuberculosis (MDR-TB) is a particular threat to the populations of resource-limited countries. Although inadequate treatment of TB has been identified as a major underlying cause of drug resistance, essential information to inform changes in health service delivery and policy is missing. We investigate factors that may be driving the emergence of MDR-TB in Myanmar, a country where investment and health system reforms are ongoing to address the unexplained, high occurrence of MDR-TB. We conducted a multi-centre, retrospective case-control study in 10 townships across Yangon...
October 1, 2017: Health Policy and Planning
https://www.readbyqxmd.com/read/29027744/concise-review-induced-pluripotent-stem-cell-models-for-neuropsychiatric-diseases
#10
REVIEW
Abidemi Adegbola, Luke A Bury, Chen Fu, Meixiang Zhang, Anthony Wynshaw-Boris
The major neuropsychiatric conditions of schizophrenia, affective disorders, and infantile autism are characterized by chronic symptoms of episodic, stable, or progressive nature that result in significant morbidity. Symptomatic treatments are the mainstay but do not resolve the underlying disease processes, which are themselves poorly understood. The prototype psychotropic drugs are of variable efficacy, with therapeutic mechanisms of action that are still uncertain. Thus, neuropsychiatric disorders are ripe for new technologies and approaches with the potential to revolutionize mechanistic understanding and drive the development of novel targeted treatments...
October 13, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29024838/organ-on-chip-models-of-cancer-metastasis-for-future-personalized-medicine-from-chip-to-the-patient
#11
REVIEW
D Caballero, S Kaushik, V M Correlo, J M Oliveira, R L Reis, S C Kundu
Most cancer patients do not die from the primary tumor but from its metastasis. Current in vitro and in vivo cancer models are incapable of satisfactorily predicting the outcome of various clinical treatments on patients. This is seen as a serious limitation and efforts are underway to develop a new generation of highly predictive cancer models with advanced capabilities. In this regard, organ-on-chip models of cancer metastasis emerge as powerful predictors of disease progression. They offer physiological-like conditions where the (hypothesized) mechanistic determinants of the disease can be assessed with ease...
October 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/29023170/ampa-receptors-and-perampanel-behind-selected-epilepsies-current-evidence-and-future-perspectives
#12
Carlo Di Bonaventura, Angelo Labate, Marta Maschio, Stefano Meletti, Emilio Russo
The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are the major mediators of glutamate-mediated excitatory neurotransmission, and are critical for synchronization and spread of epileptic activity. Areas covered. AMPA receptor antagonists have been also developed as antiepileptic drugs and perampanel (PER) is the first highly selective, non-competitive AMPA-type glutamate receptor antagonist that is available on the market. It is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures in idiopathic generalized epilepsy, in patients aged ≥ 12 years...
October 12, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29022837/critical-parameters-for-particle-based-pulmonary-delivery-of-chemotherapeutics
#13
Ali Dabbagh, Noor Hayaty Abu Kasim, Chai Hong Yeong, Tin Wui Wong, Noorsaadah Abdul Rahman
Targeted delivery of chemotherapeutics through the respiratory system is a potential approach to improve drug accumulation in the lung tumor, while decreasing their negative side effects. However, elimination by the pulmonary clearance mechanisms, including the mucociliary transport system, and ingestion by the alveolar macrophages, rapid absorption into the blood, enzymatic degradation, and low control over the deposition rate and location remain the main complications for achieving an effective pulmonary drug delivery...
October 12, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/29020948/informed-walks-whispering-hints-to-gene-hunters-inside-networks-jungle
#14
Marilena M Bourdakou, George M Spyrou
BACKGROUND: Systemic approaches offer a different point of view on the analysis of several types of molecular associations as well as on the identification of specific gene communities in several cancer types. However, due to lack of sufficient data needed to construct networks based on experimental evidence, statistical gene co-expression networks are widely used instead. Many efforts have been made to exploit the information hidden in these networks. However, these approaches still need to capitalize comprehensively the prior knowledge encrypted into molecular pathway associations and improve their efficiency regarding the discovery of both exclusive subnetworks as candidate biomarkers and conserved subnetworks that may uncover common origins of several cancer types...
October 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29020637/combinatorial-microenvironments-impose-a-continuum-of-cellular-responses-to-a-single-pathway-targeted-anti-cancer-compound
#15
Chun-Han Lin, Tiina Jokela, Joe Gray, Mark A LaBarge
Tumor microenvironments are a driver of resistance to anti-cancer drugs. Dissecting cell-microenvironment interactions into tractable units of study presents a challenge. Here, we assess the impact of hundreds of tumor-inspired microenvironments, in parallel, on lapatinib responses in four cancer cell lines. Combinations of ECM and soluble factors were printed on stiffness-tunable substrata to generate a collection of controlled microenvironments in which to explore cell-based functional responses. Proliferation, HER2 protein expression and phosphorylation, and morphology were measured in single cells...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29019066/release-mechanism-between-ion-osmotic-pressure-and-drug-release-in-ionic-driven-osmotic-pump-tablets-i
#16
Lizhen Cheng, Siqi Gao, Defang Ouyang, Haiying Wang, Yongfei Wang, Weisan Pan, Xinggang Yang
The objective of this study was to develop an authentic ionic-driven osmotic pump system and investigate the release mechanism, simultaneously exploring the in vitro and in vivo correlation of the ionic-driven osmotic pump tablet. A comparison of the ionic-driven and conventional theophylline osmotic pump, the influence of pH and the amount of sodium chloride on drug release, the relationship between the ionic osmotic pressure and the drug release, and the pharmacokinetics experiment in beagle dogs were investigated...
October 10, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29018642/pulmonary-embolism-secondary-to-testosterone-enhancing-herbal-supplement-use
#17
Steven M Nguyen, Nway Ko Ko, Asad S Sattar, Esra Gucuk Ipek, Sayed Ali
Decreased testosterone levels in men are often a normal sign of aging. Testosterone replacement therapy (TRT) is a well-established option for those with symptomatic hypogonadism related to low testosterone levels. Conversely, designer herbal supplements in the context of testosterone supplementation are poorly studied, yet remain popular among aging men who seek the well-known, often enhancing, effects of testosterone that involve muscle mass and sexual function/drive. In 2014, the Food and Drug Administration (FDA) issued a warning about the significant risk of venous clots secondary to testosterone product use...
August 6, 2017: Curēus
https://www.readbyqxmd.com/read/29016792/antidepressant-like-actions-of-inhibitors-of-poly-adp-ribose-polymerase-in-rodent-models
#18
Gregory A Ordway, Attila Szebeni, Liza J Hernandez, Jessica D Crawford, Katalin Szebeni, Michelle J Chandley, Katherine C Burgess, Corwin Miller, Erol Bakkalbasi, Russell W Brown
Background: Many patients suffering from depressive disorders are refractory to treatment with currently available antidepressant medications, while many more exhibit only a partial response. These factors drive research to discover new pharmacological approaches to treat depression. Numerous studies demonstrate evidence of inflammation and elevated oxidative stress in major depression. Recently, major depression has been shown to be associated with elevated levels of DNA oxidation in brain cells, accompanied by increased gene expression of the nuclear base excision repair enzyme, poly(ADP-ribose) polymerase-1...
August 3, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28989087/catanionic-systems-in-nanotherapeutics-biophysical-aspects-and-novel-trends-in-drug-delivery-applications
#19
REVIEW
Vivek V Dhawan, Mangal S Nagarsenker
Mixtures of surfactants can result in formation of various structures like micelles, vesicles and inverted micelles. Catanionic vesicular systems are preferred on account of their ease of formation and thermodynamic stability. Furthermore, their charge and surfactant properties render them as useful vehicles for DNA delivery and cytotoxic compounds. They suffer from disadvantages of being leaky and yielding low encapsulation efficiencies which are averse to drug delivery purposes. Extensive efforts are being undertaken to overcome these barriers and render these vesicles amenable to spatial placement and temporal delivery of drugs...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28987936/hmg-coa-synthase-2-drives-brain-metabolic-reprogramming-in-cocaine-exposure
#20
Xue Shao, Yunxuan Tang, Hailei Long, Hui Gu, Jie Zhang, Pengchi Deng, Yinglan Zhao, Xiaobo Cen
The brain is a high energy-consuming organ that typically utilizes glucose as the main energy source for cerebral activity. When glucose becomes scarce under conditions of stress, ketone bodies, such as β-hydroxybutyrate, acetoacetate and acetone, become extremely important. Alterations in brain energy metabolism have been observed in psychostimulant abusers; however, the mode of brain metabolic programming in cocaine dependence remains largely unknown. Here, we profiled the metabolites and metabolic enzymes from brain nucleus accumbens (NAc) of mice exposed to cocaine...
October 4, 2017: Neuropharmacology
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