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https://www.readbyqxmd.com/read/28647443/dermal-and-transdermal-delivery-of-pharmaceutically-relevant-macromolecules
#1
REVIEW
S Münch, J Wohlrab, R H H Neubert
The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin...
June 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#2
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28646221/aberrant-activation-of-the-human-sex-determining-gene-in-early-embryonic-development-results-in-postnatal-growth-retardation-and-lethality-in-mice
#3
Tatsuo Kido, Zhaoyu Sun, Yun-Fai Chris Lau
Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY(ON)) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645238/new-world-arenavirus-biology
#4
Nicolás Sarute, Susan R Ross
Hemorrhagic fevers caused by viruses were identified in the late 1950s in South America. These viruses have existed in their hosts, the New World rodents, for millions of years. Their emergence as infectious agents in humans coincided with changes in the environment and farming practices that caused explosions in their host rodent populations. Zoonosis into humans likely occurs because the pathogenic New World arenaviruses use human transferrin receptor 1 to enter cells. The mortality rate after infection with these viruses is high, but the mechanism by which disease is induced is still not clear...
June 23, 2017: Annual Review of Virology
https://www.readbyqxmd.com/read/28644609/galnac-tyrosine-is-a-ligand-of-plant-lectins-antibodies-and-human-and-murine-macrophage-galactose-type-lectins
#5
Ruslan Gibadullin, David Wayne Farnsworth, Joseph J Barchi, Jeffrey C Gildersleeve
In 2011, a new type of protein O-glycosylation was discovered in which N-acetylgalactosamine is attached to the side chain of tyrosine (GalNAc-Tyr). While present on dozens of proteins, the biological roles of GalNAc-Tyr are unknown. To gain insight into this new type of modification, we synthesized a group of GalNAc-Tyr glycopeptides, constructed microarrays, and evaluated potential recognition of GalNAc-Tyr by a series of glycan-binding proteins. Through a series of >150 microarray experiments, we assessed binding properties of a variety of plant lectins, monoclonal antibodies, and endogenous lectins...
June 23, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28644482/one-thousand-fold-enhancement-of-high-field-liquid-nuclear-magnetic-resonance-signals-at-room-temperature
#6
Guoquan Liu, Marcel Levien, Niels Karschin, Giacomo Parigi, Claudio Luchinat, Marina Bennati
Nuclear magnetic resonance (NMR) is a fundamental spectroscopic technique for the study of biological systems and materials, molecular imaging and the analysis of small molecules. It detects interactions at very low energies and is thus non-invasive and applicable to a variety of targets, including animals and humans. However, one of its most severe limitations is its low sensitivity, which stems from the small interaction energies involved. Here, we report that dynamic nuclear polarization in liquid solution and at room temperature can enhance the NMR signal of (13)C nuclei by up to three orders of magnitude at magnetic fields of ∼3 T...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28644443/unexpected-genomic-features-in-widespread-intracellular-bacteria-evidence-for-motility-of-marine-chlamydiae
#7
Astrid Collingro, Stephan Köstlbacher, Marc Mussmann, Ramunas Stepanauskas, Steven J Hallam, Matthias Horn
Chlamydiae are obligate intracellular bacteria comprising important human pathogens and symbionts of protists. Molecular evidence indicates a tremendous diversity of chlamydiae particularly in marine environments, yet our current knowledge is based mainly on terrestrial representatives. Here we provide first insights into the biology of marine chlamydiae representing three divergent clades. Our analysis of single-cell amplified genomes revealed hallmarks of the chlamydial lifestyle, supporting the ancient origin of their characteristic developmental cycle and major virulence mechanisms...
June 23, 2017: ISME Journal
https://www.readbyqxmd.com/read/28643464/adiponectin-isoform-patterns-in-ethnic-specific-adipoq-mutation-carriers-the-iras-family-study
#8
Keri L Tabb, Chuan Gao, Pamela J Hicks, Gregory A Hawkins, Jerome I Rotter, Yii-Der Ida Chen, Xiuqing Guo, Jill M Norris, Carlos Lorenzo, Barry I Freedman, Donald W Bowden, Nicholette D Palmer
OBJECTIVE: Adiponectin is found in human serum in three groups of multimers (high molecular weight [HMW], medium molecular weight [MMW], and low molecular weight [LMW]). Two ethnic-specific variants in ADIPOQ, G45R (Hispanic-Americans) and R55C (African-Americans), were previously reported. Although carriers of both variants had mean adiponectin levels ≤ 20% of those of noncarriers, they were not clinically different from noncarriers. To compare carriers of both variants and noncarriers, relative quantification of adiponectin isoforms to total adiponectin was performed on serum samples...
June 23, 2017: Obesity
https://www.readbyqxmd.com/read/28643176/a-promising-tool-in-retina-regeneration-current-perspectives-and-challenges-when-using-mesenchymal-progenitor-stem-cells-in-veterinary-and-human-ophthalmological-applications
#9
REVIEW
Anna Cislo-Pakuluk, Krzysztof Marycz
Visual impairment is a common ailment of the current world population, with more exposure to CCD screens and fluorescent lighting, approximately 285 billion people suffer from this deficiency and 13% of those are considered clinically blind. More common causes for visual impairment include age-related macular degeneration (AMD), glaucoma and diabetic retinopathy (Zhu et al. Molecular Medicine Reports, 2015; Kolb et al. 2007; Machalińska et al. Current Eye Research, 34(9),748-760, 2009) among a few. As cases of retinal and optic nerve diseases rise, it is vital to find a treatment, which has led to investigation of the therapeutic potential of various stem cells types (Bull et al...
June 22, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28643132/integrated-inflammatory-stress-itis-model
#10
Elisabeth O Bangsgaard, Poul G Hjorth, Mette S Olufsen, Jesper Mehlsen, Johnny T Ottesen
During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic-Pituitary-Adrenal (HPA) axis. The inflammatory response is activated acutely by pathogen- or damage-related molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model...
June 22, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28642844/role-of-bacterioferritin-ferritin-in-m-tuberculosis-pathogenesis-and-drug-resistance-a-future-perspective-by-interactomic-approach
#11
Divakar Sharma, Deepa Bisht
Tuberculosis is caused by Mycobacterium tuberculosis, one of the most successful and deadliest human pathogen. Aminoglycosides resistance leads to emergence of extremely drug resistant strains of M. tuberculosis. Iron is crucial for the biological functions of the cells. Iron assimilation, storage and their utilization is not only involved in pathogenesis but also in emergence of drug resistance strains. We previously reported that iron storing proteins (bacterioferritin and ferritin) were found to be overexpressed in aminoglycosides resistant isolates...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28642381/chemical-transformation-of-xenobiotics-by-the-human-gut-microbiota
#12
REVIEW
Nitzan Koppel, Vayu Maini Rekdal, Emily P Balskus
The human gut microbiota makes key contributions to the metabolism of ingested compounds (xenobiotics), transforming hundreds of dietary components, industrial chemicals, and pharmaceuticals into metabolites with altered activities, toxicities, and lifetimes within the body. The chemistry of gut microbial xenobiotic metabolism is often distinct from that of host enzymes. Despite their important consequences for human biology, the gut microbes, genes, and enzymes involved in xenobiotic metabolism are poorly understood...
June 23, 2017: Science
https://www.readbyqxmd.com/read/28642245/a-reporter-mouse-model-for-in-vivo-tracing-and-in-vitro-molecular-studies-of-melanocytic-lineage-cells-and-their-diseases
#13
Melissa Crawford, Valerie Leclerc, Lina Dagnino
Alterations in melanocytic lineage cells give rise to a plethora of distinct human diseases, including neurocristopathies, cutaneous pigmentation disorders, loss of vision and hearing, as well as melanoma. Understanding the ontogeny and biology of melanocytic cells, as well as how they interact with their surrounding environment, are key steps in the development of therapies for diseases that involve this cell lineage. Efforts to culture and characterize primary melanocytes from normal or genetically engineered mouse models have at times yielded contrasting observations...
June 22, 2017: Biology Open
https://www.readbyqxmd.com/read/28642126/molecular-and-hydrodynamic-properties-of-human-epidermal-growth-factor-receptor-her2-extracellular-domain-and-its-homodimer-experiments-and-multi-scale-simulations
#14
J F Vega, J Ramos, V Cruz, E Vicente-Alique, E Sánchez-Sánchez, A Sánchez-Fernández, Y Wang, P Hu, J Cortés, J Martínez-Salazar
BACKGROUND: In a broad range of human carcinomas gene amplification leads to HER2 overexpression, which has been proposed to cause spontaneous dimerization and activation in the absence of ligand. This makes HER2 attractive as a therapeutic target. However, the HER2 homodimerization mechanism remains unexplored. It has been suggested that the "back-to-back" homodimer does not form in solution. Notwithstanding, very recently the crystal structure of the HER2 extracellular domain homodimer formed with a "back-to-head" interaction has been resolved...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28640705/genomic-analysis-of-childhood-brain-tumors-methods-for-genome-wide-discovery-and-precision-medicine-become-mainstream
#15
Stephen C Mack, Paul A Northcott
Recent breakthroughs in next-generation sequencing technology and complementary genomic platforms have transformed our capacity to interrogate the molecular landscapes of human cancers, including childhood brain tumors. Numerous high-throughput genomic studies have been reported for the major histologic brain tumor entities diagnosed in children, including interrogations at the level of the genome, epigenome, and transcriptome, many of which have yielded essential new insights into disease biology. The nature of these discoveries has been largely platform dependent, exemplifying the usefulness of applying different genomic and computational strategies, or integrative approaches, to address specific biologic and/or clinical questions...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28640660/chromosome-territory-relocation-paradigm-during-dna-damage-response-some-insights-from-molecular-biology-to-physics
#16
Sarosh N Fatakia, Mugdha Kulashreshtha, Ishita S Mehta, Basuthkar J Rao
Among the many facets of DNA damage response (DDR), relocation of chromosome territories (CTs) is most intriguing. We have previously reported that cisplatin induced DDR in human dermal fibroblasts led to relocation of CTs 12, 15 from the nuclear periphery to its interior while CTs 19, 17 repositioned from the interior to its periphery. Studies of CT relocation remain nascent as we begin unraveling the role of key players in DDR to demonstrate its mechanistic basis. Consolidating our recent reports, we argue that γH2AX-signaling leads to enhanced recruitment of nuclear myosin 1 (NM1) to chromatin, which via its motor function, results in CT repositioning...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28640080/immature-enteric-ganglion-cells-were-observed-in-a-13-year-old-colon-signet-ring-cell-carcinoma-patient-a-case-report-and-literature-review
#17
Huili Li, Kun Huang, Hui Wang, Lin Wang, Ming Yang, Lixia Wang, Rong Lin, Hongli Liu, Jinbo Gao, Xiaoming Shuai, Xinghua Liu, Kaixiong Tao, Guobin Wang, Zheng Wang
RATIONALE: All the enteric ganglion cells are fully mature by 2 to 5 years of age in human. No one had reported the presentation of immature enteric ganglion cells in elder ones. Colorectal carcinoma is also rare in the adolescent population. The coincidence of these 2 rare events in a 13-year-old boy has never been reported elsewhere, which may suggest some linkage between them. PATIENT CONCERN: A 13-year-old boy presented with progressive abdominal pain and melena for 3 months...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639379/the-in-vitro-and-in-vivo-biological-activities-of-the-leaf-of-cape-myrtle-myrsine-africana-l
#18
Hina Gul, Mushtaq Ahmad, Muhammad Zafar, M Shareez Ahmad, AmbreenAbid, Syeda Hira, Imam Shah, Muhammad Gulfraz
The cape myrtle, Myrsine africana L., is a widely used medicinal plant, which has not been well investigated. We assessed the in vivo hepatoprotective and in vitro antiproliferative and antioxidant effects of leaf extracts of M. africana chemically profiled using high-performance liquid chromatography. Three flavonoids were quantified, and gas chromatography-mass spectrometry analysis revealed the presence of common fatty acids. The animal study was conducted on mice treated with CCl4, using three doses each of the methanol and chloroform extract (100, 200 and 300 mg/kg b...
June 22, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28639323/molecular-interactions-of-dioxins-and-dlcs-with-the-xenosensors-pxr-and-car-an-in-silico-risk-assessment-approach
#19
Garima Verma, Mohemmed Faraz Khan, Mohammad Shaquiquzzaman, Wasim Akhtar, Mymoona Akhter, Syed Misbahul Hasan, Mohammad Mumtaz Alam
Dioxins and dioxin-like compounds (DLCs) are known to cause endocrine disruption in humans and animals. Being lipophilic xenobiotic chemicals, they can be easily absorbed into the biological system from the surrounding environments, thereby causing various health dysfunctions. In the present study, a total of 100 dioxins and DLCs were taken, and their binding pattern was assessed with the xenosensors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in comparison with the corresponding known inhibitors and a well-studied endocrine disrupting xenobiotic, bisphenol A (BPA)...
June 22, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28639188/small-rna-guided-transcriptional-gene-activation-rnaa-in-mammalian-cells
#20
Long-Cheng Li
Small RNA partnering with Argonaute (Ago) proteins plays important roles in diverse biological processes mainly by suppressing the expression of cognate target sequences. Mounting evidence reveals that the small RNA-Ago pathway can also positively regulate gene expression, a phenomenon termed as RNA activation (RNAa), which is evolutionarily conserved from Caenorhabditis elegans to human. In this chapter, I provide a general overview of mammalian RNAa phenomena and their basic characteristics and discuss recent advances toward understanding the nature of the molecular machinery responsible for RNAa and the development of RNAa-based research tools and therapeutics...
2017: Advances in Experimental Medicine and Biology
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