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https://www.readbyqxmd.com/read/29241294/early-stage-formulation-considerations
#1
Robert W Lee, Mark Mitchnick
When a drug candidate-i.e., a new chemical entity (NCE) or new molecular entity (NME)-is discovered, there is a requirement to identify a vehicle for in vitro and/or in vivo evaluation to assess the activity and/or toxicity of the compound (here we refer to the biologically active compound as the active pharmaceutical ingredient: API). Ideally, this vehicle will not impart any biological activity or any toxicity that would mask or confound the effects of the API. At this early stage in development, and given the high attrition rates of drug candidates in discovery, it does not make sense to fully characterize the API-speed and cost are generally the driving factors...
December 14, 2017: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/29241284/-life-is-short-rejuvenation-and-immortality-from-a-historical-perspective
#2
Daniel Schäfer
To be young and immortal: That is the dream of humanity. Medical and civilizing progress have led to a life expectancy unthinkable a few centuries ago. Physicians wonder where it will all end. And after all, does it make sense to live forever? A look back in history and literature can help to relativize (post) modern utopias.
December 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29241259/-competence-based-catalogue-of-learning-objectives-for-rehabilitation-physical-medicine-naturopathic-treatment-revised-version-joint-recommendations-of-the-german-society-of-rehabilitation-science-and-the-german-society-of-physical-medicine-and-rehabilitation
#3
Wilfried Mau, Max Emanuel Liebl, Ruth Deck, Uwe Lange, Ulrich Christian Smolenski, Susanne Walter, Christoph Gutenbrunner
Since the first publication of learning objectives for the interdisciplinary subject "Rehabilitation, Physical Medicine, Naturopathic Treatment" in undergraduate medical education in 2004 a revision is reasonable due to heterogenous teaching programmes in the faculties and the introduction of the National Competence Based Catalogue of Learning Objectives in Medicine as well as the "Masterplan Medical Education 2020". Therefore the German Society of Rehabilitation Science and the German Society of Physical Medicine and Rehabilitation started a structured consensus process using the DELPHI-method to reduce the learning objectives and arrange them more clearly...
December 2017: Die Rehabilitation
https://www.readbyqxmd.com/read/29241219/yap-inhibits-the-apoptosis-and-migration-of-human-rectal-cancer-cells-via-suppression-of-jnk-drp1-mitochondrial-fission-htra2-omi-pathways
#4
Haijun Li, Fucheng He, Xin Zhao, Yuan Zhang, Xi Chu, Chunlan Hua, Yunhui Qu, Yu Duan, Liang Ming
BACKGROUND/AIMS: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo-Yap pathway in human rectal cancer tumorigenesis and metastasis. METHODS: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining...
December 12, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29241197/renoprotective-effects-of-metformin
#5
Marc E De Broe, Farshad Kajbaf, Jean-Daniel Lalau
BACKGROUND/AIMS: It has become clear that metformin exerts pleiotropic actions beyond its glucose-lowering agent effect. In this review, we summarise the state of the art concerning the potential renoprotective effects of metformin in vitro, animal models and clinical nephrology. METHODS: A literature search was performed in PUBMED, ScienceDirect, between January 1957 and March 2017 using the following keywords: "metformin," "nephroprotection," "renoprotection," "survival," "renal failure," "chronic kidney diseases," "fibrosis," "polycystic kidney disease" and "microalbuminuria...
December 14, 2017: Nephron
https://www.readbyqxmd.com/read/29241192/microrna-92a-3p-regulates-aggrecanase-1-and-aggrecanase-2-expression-in-chondrogenesis-and-il-1%C3%AE-induced-catabolism-in-human-articular-chondrocytes
#6
Guping Mao, Peihui Wu, Ziji Zhang, Zhiqi Zhang, Weiming Liao, Yukang Li, Yan Kang
BACKGROUND/AIMS: Aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5) are secreted enzymes belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family that play significant roles in the progression of osteoarthritis (OA). Here, we aimed to determine whether the expression of ADAMTS-4/5 in chondrogenesis and inflammation is regulated by microRNA-92a-3p (miR-92a-3p). METHODS: MiR-92a-3p and ADAMTS-4/5 expressions were determined by quantitative polymerase chain reaction (qPCR)...
November 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29241170/rationale-for-aggressive-resection-and-general-surgical-principles-for-intracranial-gliomas
#7
Ian E McCutcheon, Mikhail F Chernov
Given the infiltrative nature of gliomas, controversy has long persisted over the value of their aggressive surgical removal. Nevertheless, in recent decades, the balance of opinion in neurosurgical oncology has shifted from a more nihilistic view that led to many patients' receiving stereotactic biopsy or very limited debulking of lesions for tissue diagnosis only, to more extensive tumor resections which relieve mass effect, lower intracranial pressure, reduce accompanying brain edema, and attenuate dependence on steroids...
2018: Progress in Neurological Surgery
https://www.readbyqxmd.com/read/29241166/the-clinical-efficacy-of-radium-223-for-bone-metastasis-in-patients-with-castration-resistant-prostate-cancer-an-italian-clinical-experience
#8
Rossella De Luca, Renato Patrizio Costa, Vincenzo Tripoli, Alessandra Murabito, Giuseppe Cicero
BACKGROUND/AIM: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. SUBJECTS AND METHODS: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated...
December 15, 2017: Oncology
https://www.readbyqxmd.com/read/29241141/plasma-exchange-in-severe-acute-relapses-of-multiple-sclerosis-results-from-a-portuguese-cohort
#9
Inês Correia, Joana Jesus Ribeiro, Luís Isidoro, Sónia Batista, Carla Nunes, Carmo Macário, Catarina Borges, Jorge Tomaz, Lívia Sousa
BACKGROUND: Relapses in Multiple Sclerosis (MS) are often associated with significant disability impairment which is resultant from poor response to corticosteroids. In such severe cases, plasma exchange (PLEX) may be used, although only a few studies with MS patients have been reported. Our objective was to evaluate the effectiveness of PLEX in severe relapses of MS. METHODS: Retrospective study of MS patients treated with PLEX in acute relapses. Data regarding EDSS, annualized relapse rate (ARR), treatment with corticosteroids, number of PLEX sessions, adverse events, and gadolinium enhancement in brain MRI were analysed...
December 7, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29241112/chromium-isotope-fractionation-during-cr-vi-reduction-in-a-methane-based-hollow-fiber-membrane-biofilm-reactor
#10
Yong-Ze Lu, Guo-Jun Chen, Ya-Nan Bai, Liang Fu, Li-Ping Qin, Raymond Jianxiong Zeng
Chromium (Cr) isotope fractionation analysis is a promising tool for monitoring Cr(VI) reduction in natural aqueous systems. In addition, large amounts of CH4 in natural aqueous sediments are oxidized to CO2 through methanotrophs, thereby mitigating emissions to the atmosphere. However, the investigations on the Cr(VI) reduction process with methanotrophs, and the associated Cr isotope fractionation patterns are scarce. In this study, we have shown that Cr(VI) reduction can occur in the presence of CH4 as the sole electron donor in a hollow-fiber membrane reactor (HfMBR) after direct bacteria enrichment from sediment samples...
December 7, 2017: Water Research
https://www.readbyqxmd.com/read/29241110/design-synthesis-and-initial-evaluation-of-affinity-based-small-molecular-probe-for-detection-of-wdr5
#11
Wei-Lin Chen, Dong-Dong Li, Zhi-Hui Wang, Xiao-Li Xu, Xiao-Jin Zhang, Zheng-Yu Jiang, Xiao-Ke Guo, Qi-Dong You
WDR5, a subunit of the SET/MLL complex, plays critical roles in various biological progresses and are abnormally expressed in many cancers. Here we report the design, synthesis, and biochemical characterization of a new chemical tool to capture WDR5 protein. The probe is a biotinylated version of compound 30 that is a potent WDR5 inhibitor we previously reported. Importantly, the probe displayed high affinity to WDR5 protein in vitro binding potency and showed the ability in specifically and real time monitoring WDR5 protein...
November 28, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29241100/the-effect-of-spatial-auditory-landmarks-on-ambulation
#12
Adham M Karim, Kavelin Rumalla, Laurie A King, Timothy E Hullar
The maintenance of balance and posture is a result of the collaborative efforts of vestibular, proprioceptive, and visual sensory inputs, but a fourth neural input, audition, may also improve balance. Here, we tested the hypothesis that auditory inputs function as environmental spatial landmarks whose effectiveness depends on sound localization ability during ambulation. Eight blindfolded normal young subjects performed the Fukuda-Unterberger test in three auditory conditions: silence, white noise played through headphones (head-referenced condition), and white noise played through a loudspeaker placed directly in front at 135 centimeters away from the ear at ear height (earth-referenced condition)...
December 5, 2017: Gait & Posture
https://www.readbyqxmd.com/read/29241091/the-effectiveness-of-group-otago-exercise-program-on-physical-function-in-nursing-home-residents-older-than-65years-a-randomized-controlled-trial
#13
Mirjana Kocic, Zorica Stojanovic, Dejan Nikolic, Milica Lazovic, Rade Grbic, Lidija Dimitrijevic, Marina Milenkovic
AIM: To examine whether the 6-months group-based Otago exercise program is more effective than usual care on physical function and functional independence in nursing home residents older than 65 years. METHODS: An observer-blind randomized controlled study included 77 independently walking, cognitively unimpaired residents aged 78.4±7.6years, of which 66.2% were female. Physical function was assessed at baseline, after 3 and 6months of the Otago exercise program by three performance tests: Berg Balance Scale (BBS), Timed Up and Go (TUG) and Chair Rising Test (CRT), and functional independence by the motor Functional Independence Measure (mFIM)...
December 10, 2017: Archives of Gerontology and Geriatrics
https://www.readbyqxmd.com/read/29241051/determination-of-lipid-profiles-in-serum-of-obese-ponies-before-and-after-weight-reduction-by-using-multi-one-dimensional-thin-layer-chromatography
#14
Ratchada Auyyuenyong, Andrea Henze, Julia Ungru, Florian J Schweigert, Jens Raila, Ingrid Vervuert
Obesity is a key component of equine metabolic syndrome, which is highly associated with laminitis. Feed restriction and/or exercise are known to alleviate the detrimental effects of insulin resistance in obese ponies. However, little is known about changes in the serum lipid patterns due to weight reduction and its association with disease outcomes. Therefore, the lipid patterns in the serum of 14 mature ponies before and after a 14-week body weight reduction program (BWRP) were investigated by multi-one-dimensional thin-layer chromatography (MOD-TLC)...
November 21, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/29241006/toxoid-vaccination-against-bacterial-infection-using-cell-membrane-coated-nanoparticles
#15
Pavimol Angsantikul, Ronnie H Fang, Liangfang Zhang
As nanoparticles exhibit unique properties attractive for vaccine development, they have been progressively implemented as antigen delivery platforms and immune potentiators. Recently, cell membrane-coated nanoparticles have provided a novel approach for intercepting and neutralizing bacterial toxins by leveraging their natural affinity to cellular membranes. Such toxin-nanoparticle assemblies, termed nanotoxoids, allow rapid loading of different types of toxins and have been investigated for their ability to effectively confer protection against bacterial infection...
December 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29240978/biomimicry-of-volatile-based-microbial-control-for-managing-emerging-fungal-pathogens
#16
REVIEW
Kyle T Gabriel, Joseph D Sexton, Christopher T Cornelison
Volatile organic compounds (VOCs) are known to be produced by a wide range of microorganisms and for a number of purposes. Volatile-based microbial inhibition in environments such as soil is well-founded, with numerous antimicrobial VOCs having been identified. Inhibitory VOCs are of interest as microbial control agents, as low concentrations of gaseous VOCs can elicit significant antimicrobial effects. Volatile organic compounds are organic chemicals typically characterized as having low molecular weight, low solubility in water, and high vapor pressure...
December 14, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29240968/monitoring-of-spoilage-associated-microbiota-on-modified-atmosphere-packaged-beef-and-differentiation-of-psychrophilic-and-psychrotrophic-strains
#17
Maik Hilgarth, Jürgen Behr, Rudi F Vogel
AIMS: This study aimed to explore the discriminatory power of MALDI-TOF MS as a high-throughput method to monitor growth dynamics of meat-spoiling bacteria on modified atmosphere packaged (MAP) beef and to differentiate psychrophilic and psychrotrophic spoilage-associated strains. METHODS AND RESULTS: MAP beef steaks were incubated for 21 days at constant 4 and 10 °C. Development of headspace gas composition, pH, CFU and spoilage-associated microbial composition were monitored...
December 14, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29240955/pine-wilt-disease-causes-cavitation-around-the-resin-canals-and-irrecoverable-xylem-conduit-dysfunction
#18
Kenichi Yazaki, Takuma Takanashi, Natsumi Kanzaki, Masabumi Komatsu, Delphis F Levia, Daisuke Kabeya, Hiroyuki Tobita, Mitsutoshi Kitao, Atsushi Ishida
Physiological mechanisms of irreversible hydraulic dysfunction in seedlings infected with pine wilt disease (PWD) are still unclear. We employed cryo-scanning electron microscopy (cryo-SEM) to investigate the temporal and spatial changes in water distribution within the xylem of the main stem of 2-year-old Japanese black pine seedlings infested by pine wood nematodes (PWNs). Our experiment was specifically designed to compare the water relations among seedlings subjected to the following water treatment and PWN combinations: (i) well-watered versus prolonged drought (no PWNs); and (ii) well-watered with PWNs versus water-stressed with PWNs (four treatments in total)...
December 12, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29240947/a-fth1-gene-pseudogene-microrna-network-regulates-tumorigenesis-in-prostate-cancer
#19
Jia Jia Chan, Zhi Hao Kwok, Xiao Hong Chew, Bin Zhang, Chao Liu, Tuck Wah Soong, Henry Yang, Yvonne Tay
Non-coding RNAs play a vital role in diverse cellular processes. Pseudogenes, which are non-coding homologs of protein-coding genes, were once considered non-functional evolutional relics. However, recent studies have shown that pseudogene transcripts can regulate their parental transcripts by sequestering shared microRNAs (miRNAs), thus acting as competing endogenous RNAs (ceRNAs). In this study, we utilize an unbiased screen to identify the ferritin heavy chain 1 (FTH1) transcript and multiple FTH1 pseudogenes as targets of several oncogenic miRNAs in prostate cancer (PCa)...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29240940/state-of-the-art-in-eukaryotic-nitrogenase-engineering
#20
Stefan Burén, Luis M Rubio
Improving the ability of plants and plant-associated organisms to fix and assimilate atmospheric nitrogen has inspired plant biotechnologists for decades, not only to alleviate negative effects on nature from increased use and availability of reactive nitrogen, but also because of apparent economic benefits and opportunities. The combination of recent advances in synthetic biology and increased knowledge about the biochemistry and biosynthesis of the nitrogenase enzyme has made the seemingly remote and for long unreachable dream more possible...
December 12, 2017: FEMS Microbiology Letters
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