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https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#1
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29342181/optimization-of-mneongreen-for-homo-sapiens-increases-its-fluorescent-intensity-in-mammalian-cells
#2
Emiko Tanida-Miyake, Masato Koike, Yasuo Uchiyama, Isei Tanida
Green fluorescent protein (GFP) is tremendously useful for investigating many cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5-times brighter than GFP and monomeric enhanced GFP and shows high photostability. The maturation half-time of mNeonGreen is about 3-fold faster than that of monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains some codons that are rarely used in Homo sapiens. For better expression of mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the control of the cytomegalovirus promoter...
2018: PloS One
https://www.readbyqxmd.com/read/29342139/structure-and-mutagenesis-reveal-essential-capsid-protein-interactions-for-kshv-replication
#3
Xinghong Dai, Danyang Gong, Hanyoung Lim, Jonathan Jih, Ting-Ting Wu, Ren Sun, Z Hong Zhou
Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer that commonly affects patients with AIDS and which is endemic in sub-Saharan Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome, as are the capsids of the eight other human herpesviruses. Capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. However, herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 Å in diameter-present a formidable challenge to atomic structure determination and functional mapping of molecular interactions...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29341349/peroxiredoxin-4-prdx4-its-critical-in-vivo-roles-in-animal-models-of-metabolic-syndrome-ranging-from-atherosclerosis-to-nonalcoholic-fatty-liver-disease
#4
REVIEW
Sohsuke Yamada, Xin Guo
The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. We generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models...
January 17, 2018: Pathology International
https://www.readbyqxmd.com/read/29340639/biomechanical-rigidity-and-quantitative-proteomics-analysis-of-segmental-regions-of-the-trabecular-meshwork-at-physiologic-and-elevated-pressures
#5
Janice A Vranka, Julia A Staverosky, Ashok P Reddy, Phillip A Wilmarth, Larry L David, Ted S Acott, Paul Russell, Vijay Krishna Raghunathan
Purpose: The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading cause of irreversible blindness worldwide, is associated with changes in the ECM of the TM. The elastic modulus of glaucomatous TM is larger than age-matched normal TM; however, the biomechanical properties of segmental low (LF) and high flow (HF) TM regions and their response to elevated pressure, are unknown. Methods: We perfused human anterior segments at two pressures using an ex vivo organ culture system...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29340222/direct-molecular-fishing-of-new-protein-partners-for-human-thromboxane-synthase
#6
A V Svirid, P V Ershov, E O Yablokov, L A Kaluzhskiy, Yu V Mezentsev, A V Florinskaya, T A Sushko, N V Strushkevich, A A Gilep, S A Usanov, A E Medvedev, A S Ivanov
Thromboxane synthase (TBXAS1) catalyzes the isomerization reaction of prostaglandin H2 producing thromboxane A2, the autocrine and paracrine factor in many cell types. A high activity and metastability by these arachidonic acid derivatives suggests the existence of supramolecular structures that are involved in the regulation of the biosynthesis and directed translocation of thromboxane to the receptor. The objective of this study was to identify TBXAS1 protein partners from human liver tissue lysate using a complex approach based on the direct molecular fishing technique, LC-MS/MS protein identification, and protein-protein interaction validation by surface plasmon resonance (SPR)...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339972/evaluation-of-green-tea-extract-as-a-safe-personal-hygiene-against-viral-infections
#7
Yun Ha Lee, Yo Han Jang, Young-Seok Kim, Jinku Kim, Baik Lin Seong
Background: Viral infections often pose tremendous public health concerns as well as economic burdens. Despite the availability of vaccines or antiviral drugs, personal hygiene is considered as effective means as the first-hand measure against viral infections. The green tea catechins, in particular, epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity. In this study, we evaluated the green tea extract as a safe personal hygiene against viral infections. Results: Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29339744/human-caspase-4-detects-tetra-acylated-lps-and-cytosolic-francisella-and-functions-differently-from-murine-caspase-11
#8
Brice Lagrange, Sacha Benaoudia, Pierre Wallet, Flora Magnotti, Angelina Provost, Fanny Michal, Amandine Martin, Flaviana Di Lorenzo, Bénédicte F Py, Antonio Molinaro, Thomas Henry
Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the lipid moeity of lipopolysaccharide (LPS), to induce the activation of non-canonical inflammasome. Pathogens such as Francisella novicida express an under-acylated lipid A and escape caspase-11 recognition in mice. Here, we show that caspase-4 drives inflammasome responses to F. novicida infection in human macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be recapitulated by transfection of under-acylated LPS from different bacterial species or synthetic tetra-acylated lipid A into cytosol of human macrophage...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339716/to-explore-the-mechanism-of-the-grm4-gene-in-osteosarcoma-by-rna-sequencing-and-bioinformatics-approach
#9
Yunguo Pang, Jinmin Zhao, Mitra Fowdur, Yun Liu, Hao Wu, Maolin He
BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the pathogenesis of osteosarcoma. The objective of this study was to explore the underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19 cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of the highest GRM4 expression were transfected with lentivirus-mediated small interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4 gene silencing were screened through RNA sequencing, and analyzed by bioinformatics...
January 17, 2018: Medical Science Monitor Basic Research
https://www.readbyqxmd.com/read/29339444/light-hvem-signaling-in-keratinocytes-controls-development-of-dermatitis
#10
Rana Herro, Jr-Wen Shui, Sonja Zahner, Daniel Sidler, Yuko Kawakami, Toshiaki Kawakami, Koji Tamada, Mitchell Kronenberg, Michael Croft
Dermatitis is often associated with an allergic reaction characterized by excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal lymphopoietin (TSLP) are thought to be instrumental for the development of this type of skin disorder, other cytokines may be critical. Here, we show that the tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes) is required for experimental atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and production of periostin, a matricellular protein that contributes to the clinical features of atopic dermatitis as well as other skin diseases such as scleroderma...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29339308/antibiotic-resistance-and-virulence-traits-of-bacterial-pathogens-from-infected-freshwater-fish-labeo-rohita
#11
Dharmaraj Ramesh, Sami Souissi
Bacterial infectious diseases are a main dangerous problem in Aquaculture farming. It causes multiple diseases in fish as well as in human being and it has considerable virulence potential. In this connection, the moot of study focus to discriminate bacterial isolates recovered from naturally diseased Labeo rohita fish and their virulent characteristics. Based on the β-haemolysis factor, four isolates (KADR11, KADR12, KADR13 and KADR14) were selected for further delineation. These bacterial isolates showed high similarity with Providencia rettgeri, Aeromonas sp...
January 12, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29339228/stability-and-plasmatic-protein-binding-of-novel-zidovudine-prodrugs-targeting-site-ii-of-human-serum-albumin
#12
Esteban M Schenfeld, Sergio R Ribone, Mario A Quevedo
Despite its vastly demonstrated clinical efficacy, zidovudine (AZT) exhibits several suboptimal pharmacokinetic properties. In particular, its short plasmatic half-life (t1/2 ~ 1 h) is related to its low bound fraction to whole plasmatic proteins and in particular to human serum albumin (HSA). The design of prodrugs constitutes a promising strategy to enhance AZT pharmacokinetic properties, including its affinity for HSA. Recently, we reported the synthesis and chemical stability evaluation of three novel prodrugs of AZT obtained by derivatization with dicarboxylic acids (1-3)...
January 12, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29339058/carboxylic-group-riched-graphene-oxide-based-disposable-electrochemical-immunosensor-for-cancer-biomarker-detection
#13
Sajid Rauf, Geetesh K Mishra, Jahanzaib Azhar, Rupesh K Mishra, K Yugender Goud, Muhammad Azhar Hayat Nawaz, Jean Louis Marty, Akhtar Hayat
In this work, we have developed for the first time a carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection using methylene blue (MB). The developed immunosensor is highly sensitive for detection of biomarker Mucin1 (MUC1) in human serum samples. Development of this disposable electrochemical immunosensor was premeditated by applying specific monoclonal antibodies against MUC1. In this method, we explored highly conductive surface of carboxylic group (-COOH-) rich graphene oxide (GO) on screen-printed carbon electrodes (SPCE)...
January 12, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29338562/targeted-microbubbles-with-ultrasound-irradiation-and-pd-1-inhibitor-to-increase-antitumor-activity-in-b-cell-lymphoma
#14
Shiya Zheng, Dan Song, Xiaoxiao Jin, Haijun Zhang, Mohanad Aldarouish, Yan Chen, Cailian Wang
AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro-environment become main obstacles for the effective treatment of B-cell lymphoma. In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs) were designed for exploring a combination approach of targeted microbubbles with ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells...
January 17, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29338033/intermittent-low-dose-carbon-monoxide-exposure-enhances-survival-and-dopaminergic-differentiation-of-human-neural-stem-cells
#15
Nanna Dreyer-Andersen, Ana Sofia Almeida, Pia Jensen, Morad Kamand, Justyna Okarmus, Tine Rosenberg, Stig Düring Friis, Alberto Martínez Serrano, Morten Blaabjerg, Bjarne Winther Kristensen, Troels Skrydstrup, Jan Bert Gramsbergen, Helena L A Vieira, Morten Meyer
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species...
2018: PloS One
https://www.readbyqxmd.com/read/29337653/safety-and-immunogenicity-of-a-meningococcal-b-recombinant-vaccine-when-administered-with-routine-vaccines-to-healthy-infants-in-taiwan-a-phase-3-open-label-randomized-study
#16
Nan-Chang Chiu, Li-Min Huang, Arnold Willemsen, Chiranjiwi Bhusal, Ashwani Kumar Arora, Zenaida Reynoso Mojares, Daniela Toneatto
Neisseria meningitidis is associated with high mortality and morbidity in infants and children worldwide. This phase 3 study (NCT02173704) evaluated safety and immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total, 225 healthy infants were randomized (2:1) to receive 4CMenB and routine vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and 12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal, hepatitis B, measles-mumps-rubella and varicella vaccines...
January 16, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29337647/compositional-assessment-of-human-tracheal-cartilage-by-infrared-spectroscopy
#17
Gary Linkov, Arash Hanifi, Farzad Yousefi, Derrick Tint, Sudheer Bolla, Nathanial Marchetti, Ahmed M S Soliman, Nancy Pleshko
Objectives To assess the potential of infrared fiber-optic spectroscopy to evaluate the compositional properties of human tracheal cartilage. Study Design Laboratory-based study. Methods Twenty human cadaveric distal tracheas were harvested (age range 20-78 years; 6 females, 14 males) for compositional analysis. Histologic staining, Fourier transform infrared imaging spectroscopy data on collagen and proteoglycan (PG) content, and near-infrared (NIR) fiber-optic probe spectroscopic data that reflect protein and water content were evaluated...
January 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29337305/host-expression-of-pd-l1-determines-efficacy-of-pd-l1-pathway-blockade-mediated-tumor-regression
#18
Heng Lin, Shuang Wei, Elaine M Hurt, Michael D Green, Lili Zhao, Linda Vatan, Wojciech Szeliga, Ronald Herbst, Paul W Harms, Leslie A Fecher, Pankaj Vats, Arul M Chinnaiyan, Christopher D Lao, Theodore S Lawrence, Max Wicha, Junzo Hamanishi, Masaki Mandai, Ilona Kryczek, Weiping Zou
Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337120/deriving-dorsal-spinal-sensory-interneurons-from-human-pluripotent-stem%C3%A2-cells
#19
Sandeep Gupta, Daniel Sivalingam, Samantha Hain, Christian Makkar, Enrique Sosa, Amander Clark, Samantha J Butler
Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29334656/activated-protein-c-suppresses-osteoclast-differentiation-via-endothelial-protein-c-receptor-protease-activated-receptor-1-sphingosine-1-phosphate-receptor-and-apolipoprotein-e-receptor-2
#20
Kakunoshin Yoshida, Nobuyuki Akita, Takayuki Okamoto, Kunihiro Asanuma, Atsumasa Uchida, Akihiro Sudo, Motomu Shimaoka, Koji Suzuki, Tatsuya Hayashi
INTRODUCTION: Bone remodeling relies on a delicate balance between formation and resorption of bone tissues, processes in which bone-forming osteoblasts and bone-resorbing osteoclasts play central roles. Recently, we reported that anticoagulant activated protein C (APC) promotes osteoblast proliferation, but the role of the blood coagulation system in bone remodeling remains unclear. In this study, to further elucidate the relationship between bone remodeling and blood coagulation, we investigated the effect of APC on osteoclast differentiation...
January 3, 2018: Thrombosis Research
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