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https://www.readbyqxmd.com/read/29684708/structural-based-design-synthesis-and-antitumor-activity-of-novel-alloxazine-analogues-with-potential-selective-kinase-inhibition
#1
Waleed H Malki, Ahmed M Gouda, Hamdy E A Ali, Rabaa Al-Rousan, Doaa Samaha, Ashraf N Abdalla, Juan Bustamante, Zakaria Y Abd Elmageed, Hamed I Ali
Protein kinases are promising therapeutic targets for cancer therapy. Here, we applied multiple approaches to optimize the potency and selectivity of our reported alloxazine scaffold. Flexible moieties at position 2 of the hetero-tricyclic system were incorporated to fit into the ATP binding site and extend to the adjacent allosteric site and selectively inhibit protein kinases. This design led to potential selective inhibition of ABL1, CDK1/Cyclin A1, FAK, and SRC kinase by 30-59%. Cytotoxicity was improved by ∼50 times for the optimized lead (10b; IC50  = 40 nM) against breast cancer (MCF-7) cells...
April 17, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29684543/molecular-characterization-of-clostridium-difficile-isolated-from-carriage-and-association-of-its-pathogenicity-to-prevalent-toxic-genes
#2
Abdulwahab Ali Abuderman, Ayesha Mateen, Rabbani Syed, Mustafa Sawsan Aloahd
BACKGROUND: There are reports of non-toxigenic C. difficile strains from asymptomatic carriers are increasing source of transmission. Asymptomatic carriage transmission in the hospital or community settings might have changed over the years. Therefore, we initiated a prospective epidemiological study to define the risk factors and pathogenicity of asymptomatic C. difficile carriage. METHODS: Stools sample from 188 subjects with diarrhoea due to C. difficile toxin and colonization without diarrhoea was subjected to routine microbial culture, molecular characterization for identification of toxin genes and mechanisms of resistance in C...
April 20, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29684455/a-novel-extracellular-copper-zinc-superoxide-dismutase-identified-from-nibea-albiflora-and-its-characteristics-under-ammonia-nitrite-stress
#3
Xiaolong Wang, Qing Song, Zhiyong Wang, Fang Han
The cDNA of EcSOD (designated as NaEcSOD), cloned and characterized from Nibea albiflora for the first time, was 1101 bp in length including 5'-untranslated region (UTR) of 224 bp, 3' UTR of 229 bp, and an open reading frame (ORF) of 648 bp encoding a polypeptide of 215 amino acids. Based on the results of GST pull-down assay and mass spectrometric identifications, a membrane protein (annexin A4) was found to specifically bind with NaEcSOD, indicating that the two proteins might be involved in antagonizing reactive oxygen species (ROS) together...
April 20, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29684359/the-g-protein-coupled-receptor-alx-fpr2-regulates-adaptive-immune-responses-in-mouse-submandibular-glands
#4
Ching-Shuen Wang, Olga J Baker
ALX/FPR2 is a G-protein-coupled receptor that has multiple binding partners, including the endogenous lipid mediators resolvin D1 (RvD1), lipoxin A4 (LXA4 ), and the Ca2+ -dependent phospholipid-binding protein Annexin A1. Previous studies demonstrated that RvD1 activates ALX/FPR2 to resolve salivary gland inflammation in the NOD/ShiLtJ mouse model for Sjögren's syndrome. Moreover, mice lacking the ALX/FPR2 display an exacerbated salivary gland inflammation in response to lipopolysaccharide. Additionally, activation of ALX/FPR2 has been shown to be important for regulating antibody production in B cells...
April 20, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29682763/differential-expression-of-annexin-2-spink1-and-hsp60-predict-progression-of-prostate-cancer-through-bifurcated-who-gleason-score-categories-in-african-american-men
#5
Desta A Beyene, Tammey J Naab, Norma F Kanarek, Victor Apprey, Ashwini Esnakula, Farahan A Khan, Marc R Blackman, Collis A Brown, Tamaro S Hudson
BACKGROUND: Although studies have observed several markers correlate with progression of prostate cancer (PCa), no specific markers have been identified that accurately predict the progression of this disease, even in African American (AA) men who are generally at higher risk than other ethnic groups. The primary goal of this study was to explore whether three markers could predict the progression of PCa. METHOD: We investigated protein expression of Annexin 2 (ANX2), serine peptidase inhibitor, kazal type 1(SPINK1)/tumor-associated trypsin inhibitor (TATI), and heat shock protein 60 (Hsp60) in 79 archival human prostate trans-rectal ultrasound (TRUS) biopsy tissues according to a modified World Health Organization (WHO) classification: normal (WHO1a), Gleason Score (GS6 (WHO1b), GS7 subgroups (WHO2 = 3 + 4, WHO3 = 4 + 3), GS8 (WHO4), and GS9-10 (WHO5)...
April 22, 2018: Prostate
https://www.readbyqxmd.com/read/29680844/utilizing-the-nanosecond-pulse-technique-to-improve-antigen-intracellular-delivery-and-presentation-to-treat-tongue-squamous-cell-carcinoma
#6
C Gao, X Zhang, J Chen, J Zhao, Y Liu, J Zhang, J Wang
BACKGROUND: Tongue squamous cell carcinoma is the most common squamous cell carcinoma of the head and neck. Immunotherapy has great potential in the treatment of tongue squamous cell carcinoma because of its unique advantages. However, the efficacy of immunotherapy is limited by the efficiency of antigen phagocytosis by immune cells. MATERIAL AND METHODS: We extracted dendritic cells (DCs) from human peripheral blood. Utilizing a nanosecond pulsed electric field (nsPEF), we deliver the tumour lysate protein into DCs and then incubate the DCs with PBMCs to obtain specific T cells to kill tumour cells...
April 22, 2018: Medicina Oral, Patología Oral y Cirugía Bucal
https://www.readbyqxmd.com/read/29680228/downregulation-of-cyclin-b1-mediated-nagilactone-e-induced-g2-phase-cell-cycle-arrest-in-non-small-cell-lung-cancer-cells
#7
Le-Le Zhang, Zhe-Ling Feng, Min-Xia Su, Xiao-Ming Jiang, Xiuping Chen, Yitao Wang, Ao Li, Li-Gen Lin, Jin-Jian Lu
Non-small cell lung cancer (NSCLC) is one of most common forms and leading causes of cancer-related mortality worldwide, and discovery of new effective drugs still remains imperative to improve the survival rate. Nagilactone E (NLE) is a natural product isolated from Podocarpus nagi seeds, which has been used as raw materials for edible oil and industrial oil extraction. This study aimed to investigate the anticancer potential of NLE against NSCLC A549 and NCI-H1975 cells. MTT assay revealed that NLE inhibited the proliferation of A549 and NCI-H1975 cells with IC50 s of 5...
April 19, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29679904/tanshinone-iia-protects-murine-chondrogenic-atdc5-cells-from-lipopolysaccharide-induced-inflammatory-injury-by-down-regulating-microrna-203a
#8
Luan Luan, Zhiyuan Liang
BACKGROUND: Osteoarthritis is the most common bone-joint disease in middle and older people all over the world. Tanshinone IIA (Tan IIA) is the main lipophilic diterpenoid isolated from the root of Salvia miltiorrhiza Bunge (Lamiaceae). This study analyzed the protective effects of Tan IIA on lipopolysaccharide (LPS)-induced murine chondrogenic ATDC5 cell inflammatory injury model. METHODS: Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Cell apoptosis was detected using Annexin V-FITC/PI staining...
April 18, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29677533/proresolving-protein-annexin-a1-the-role-in-type-2-diabetes-mellitus-and-obesity
#9
Nathalia T Pietrani, Cláudia N Ferreira, Kathryna F Rodrigues, Luiza O Perucci, Fernanda S Carneiro, Adriana A Bosco, Marina C Oliveira, Solange S Pereira, Antônio L Teixeira, Jacqueline I Alvarez-Leite, Adaliene V Ferreira, Lirlândia P Sousa, Karina B Gomes
BACKGROUND: Annexin A1 (AnxA1) is a protein involved in inflammation resolution that might be altered in obesity-associated type 2 diabetes mellitus (DM), which is a chronic inflammatory disease. The aim of this study was to evaluate AnxA1 serum levels in individuals with and without DM stratified according to the body mass index (BMI), and the dynamic of AnxA1 expression in adipose tissue from humans with obesity and non-obesity. METHODS: Serum samples were obtained from 41 patients with DM (lean, overweight and obese) and 40 controls, and adipose tissue samples were obtained from 16 individuals with obesity (with or without DM), and 15 controls...
April 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29675370/effect-of-senescence-marker-protein-30-on-the-proliferation-and-apoptosis-of-human-lens-epithelial-cells-sra01-04
#10
Xi Chen, Song-Man Li, Yan-Wei Li, Zi-Hao Han, Hao Liang
AIM: To study the effect of senescence marker protein 30 (SMP30) on the proliferation and apoptosis of human lens epithelial cell (HLEC) SRA01/04. METHODS: SMP30 overexpression (OE) and knock down (KD) type cell lines were cultivated by using two groups regucalcin (RGN; SMP30) lentiviral vectors (LV-RGN, LV-RGN-RNAi) and the respective negative control virus infect SRA01/04 cells. Western blot and real-time quantitative polymerase chain reaction (q-PCR) analysis were used to determine RGN overexpression and knock down efficiency...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29674236/sub-lethal-ultraviolet-b-irradiation-and-poly-i-c-treatment-synergistically-induced-apoptosis-of-hacat-cells-through-nf-%C3%AE%C2%BAb-pathway
#11
Wuxiyar Otkur, Weiwei Liu, Jinda Wang, Xingfan Jia, Dianchao Huang, Fang Wang, Toshihiko Hayashi, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
Ultraviolet B (UVB) irradiation exerts multiple effects on skin cells, inducing apoptosis, senescence and carcinogenesis. Toll-like receptor 3, a member of pattern recognition receptors, is reported to initiate inflammation by recognizing double-strand RNA (dsRNA) released from UVB-irradiated cells. It has not been studied, however, whether apoptosis induction in UVB irradiation is attributed to TLR3 activation. Here, we report on the pro-apoptotic role of TLR3 in UVB-irradiated epidermal cells. Poly I:C, an analogue of dsRNA that activates TLR3, was used in combination with sub-lethal UVB (4...
April 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29673196/annexins-in-glaucoma
#12
REVIEW
Timothy E Yap, Benjamin Michael Davis, Li Guo, Eduardo M Normando, Maria Francesca Cordeiro
Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis...
April 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29672621/imbalance-between-endothelial-damage-and-repair-capacity-in-chronic-obstructive-pulmonary-disease
#13
Jéssica García-Lucio, Victor I Peinado, Lluís de Jover, Roberto Del Pozo, Isabel Blanco, Cristina Bonjoch, Núria Coll-Bonfill, Tanja Paul, Olga Tura-Ceide, Joan Albert Barberà
BACKGROUND: Circulating endothelial microparticles (EMPs) and progenitor cells (PCs) are biological markers of endothelial function and endogenous repair capacity. The study was aimed to investigate whether COPD patients have an imbalance between EMPs to PCs compared to controls and to evaluate the effect of cigarette smoke on these circulating markers. METHODS: Circulating EMPs and PCs were determined by flow cytometry in 27 nonsmokers, 20 smokers and 61 COPD patients with moderate to severe airflow obstruction...
2018: PloS One
https://www.readbyqxmd.com/read/29672315/microrna-10b-promotes-apoptosis-via-jnk-pathway-in-clear-cell-renal-cell-carcinoma
#14
Jianyang Qin, Jia Zhou, Ling Teng, Ying Han
BACKGROUND/AIMS: To investigate the downregulation of microRNA (miR)-10b in clear cell renal cell carcinoma (ccRCC) and its mechanistic involvement in tumourigenesis. METHODS: The relative expression of miR-10b in ccRCC samples were determined by real-time PCR. Exogenous expression and knockdown of endogenous miR-10b were performed by transfection with indicated plasmids into 786-0 cells. Cell proliferation was evaluated using Cell Counting Kit-8 assay. Cell apoptosis was analyzed by Annexin V/propidium iodide staining...
April 19, 2018: Nephron
https://www.readbyqxmd.com/read/29671338/inhibition-of-mir-182-5p-protects-cardiomyocytes-from-hypoxia-induced-apoptosis-by-targeting-ciapin1
#15
Yunsong Zhang, Jun Fang, Huiwen Ma
Myocardial infarction (MI), a type of ischemic heart disease, is generally accompanied by cardiomyocytes apoptosis. MiRNAs play the vital roles in the development and physiology of MI. Here, we established a downregulation model of miR-182-5p in H9c2 cells under hypoxia condition for investigating the potential molecular mechanism of miR-182-5p in hypoxia-induced cardiomyocytes apoptosis (HICA). RT-qPCR indicated that miR-182-5p level exhibited a time-dependent manner increase in hypoxia-induced cells. The results of MTT and LDH assays indicated that cardiomyocytes injury was markedly amplified after hypoxia treatment...
April 19, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29669502/synthetic-diethyl-2-6-dimethyl-1-4-dihydropyridine-3-5-dicarboxylates-induce-apoptosis
#16
Seunghyun Ahn, Youngshim Lee, Jihyun Park, Junho Lee, Soon Young-Shin, Young Han Lee, Dongsoo Koh, Yoongho Lim
BACKGROUND: The Hantzsch ester, diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, has been used as a hydride donor and its various biological effects have been reported. To identify chemotherapeutic agents with apoptotic effects, 21 diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates were designed and synthesized; they have not been reported as apoptosis inducers thus far. Their structure-cytotoxicity relationships were investigated. Further biological experiments were performed on the title compound...
April 18, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29669353/cinobufagin-induces-apoptosis-in-osteosarcoma-cells-via-the-mitochondria-mediated-apoptotic-pathway
#17
Guo Dai, Di Zheng, Weichun Guo, Jian Yang, An-Yuan Cheng
BACKGROUND/AIMS: Osteosarcoma is a common primary malignant bone tumor that mainly occurs in childhood and adolescence. Despite developments in the diagnosis and treatment of osteosarcoma, the prognosis is still very poor. Cinobufagin is an active component in the anti-tumor Chinese medicine called "Chan Su", and we previously revealed that cinobufagin induced apoptosis and reduced the viability of osteosarcoma cells; however, the underlying mechanism remains to be elucidated...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29667627/propofol-inhibits-hela-cells-by-impairing-autophagic-flux-via-amp-activated-protein-kinase-ampk-activation-and-endoplasmic-reticulum-stress-regulated-by-calcium
#18
Xi Chen, Kai Li, Guoqing Zhao
BACKGROUND Propofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated. MATERIAL AND METHODS We treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29667067/a-first-in-class-inhibitor-mln4924-pevonedistat-induces-cell-cycle-arrest-senescence-and-apoptosis-in-human-renal-cell-carcinoma-by-suppressing-ube2m-dependent-neddylation-modification
#19
Bo Xu, Yuyou Deng, Ran Bi, Haoran Guo, Chang Shu, Neelam Kumari Shah, Junliang Chang, Guanchen Liu, Yujun Du, Wei Wei, Chunxi Wang
PURPOSE: MLN4924 is a second-generation inhibitor that targets ubiquitin-proteasome system by inhibiting neddylation activation enzyme (NAE), and subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs), which leads to the accumulation of CRLs substrates and hence, suppressing diverse tumor development. In this study, we investigated the potential application of this first-in-class inhibitor MLN4924 in the treatment of human renal cell carcinoma both in vitro and in vivo...
April 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29665918/-inhibitory-effect-of-histone-deacetylase-inhibitor-saha-on-proliferation-of-mouse-multiple-myeloma-cell-line-sp2-0-in-vitro-and-in-vivo
#20
Lei Huo, Chen-Yu Zhang, Yi-Fang Dang, Wan-Jun Zhang, Man-Man Liu, Lu-She Liu, Zun-Min Zhu, Na Fang, Shao-Ping Ji, Kai Sun
OBJECTIVE: To explore the anti-myeloma effect of suberoylanilide hydroxamic acid (SAHA) and on mouse myeloma cell line SP2/0 in vitro and in vivo and its mechanism. METHODS: The inhibitory effect of SAHA on SP2/0 cells was measured by CCK-8 assay,and the apoptosis and cell cycle were analyzed by flow cytometry FACS. The protein expression of Caspase-3 and p53 of SP2/0 cells treated with SAHA were examined by Western blot. Annexin V/7-AAD double staining was performed to detect the apoptosis of SP2/0 induced by SAHA in vitro...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
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