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https://www.readbyqxmd.com/read/28222398/isolation-of-a-new-resorcinolic-lipid-from-mangifera-zeylanica-hook-f-bark-and-its-cytotoxic-and-apoptotic-potential
#1
Meran Keshawa Ediriweera, Kamani Hemamala Tennekoon, Sameera Ranganath Samarakoon, Achyut Adhikari, Ira Thabrew, E Dilip de Silva
Mangifera zeylanica is a plant endemic to Sri Lanka and its bark has been used in traditional medicine to treat some cancers. This study was aimed to isolate potentially cytotoxic compound/s from the hexane extract of the bark of M. zeylanica by bio-activity guided fractionation. The structure of the isolated compound (1) was elucidated using (1)H, (13)C NMR and mass spectrometric techniques. Compound 1 was identified as a new resorcinolic lipid (5-((8Z, 11Z, 14Z)-hexatriaconta-8, 11, 14-trienyl) benzene-1,3-diol)...
February 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28215509/triphenylphosphonium-modified-poly-ethylene-glycol-poly-%C3%AE%C2%B5-caprolactone-micelles-for-mitochondria-targeted-gambogic-acid-delivery
#2
Yingqi Xu, Shengpeng Wang, Hon Fai Chan, Yuling Liu, Hui Li, Chengwei He, Zeyong Li, Meiwan Chen
Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07±11.71nm and an encapsulation efficiency of 80...
February 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28214863/stimulation-of-erythrocyte-cell-membrane-scrambling-by-c-reactive-protein
#3
Majed Abed, Christian Thiel, Syeda T Towhid, Kousi Alzoubi, Sabina Honisch, Florian Lang, Alfred Königsrainer
BACKGROUND: Eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phosphatidylserine-translocation, is triggered by fever and inflammation. Signaling includes increased cytosolic Ca2+-activity ([Ca2+]i), caspase activation, and ceramide. Inflammation is associated with increased plasma concentration of C-reactive protein (CRP). The present study explored whether CRP triggers eryptosis. METHODS: Phosphatidylserine abundance at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance and caspase-3-activity utilizing FITC-conjugated antibodies...
February 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#4
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28197319/structure-based-design-of-non-natural-peptidic-macrocyclic-mcl-1-inhibitors
#5
Jeffrey W Johannes, Stephanie Bates, Carl Beigie, Matthew A Belmonte, John Breen, Shenggen Cao, Paolo A Centrella, Matthew A Clark, John W Cuozzo, Christoph E Dumelin, Andrew D Ferguson, Sevan Habeshian, David Hargreaves, Camil Joubran, Steven Kazmirski, Anthony D Keefe, Michelle L Lamb, Haiye Lan, Yunxia Li, Hao Ma, Scott Mlynarski, Martin J Packer, Philip B Rawlins, Daniel W Robbins, Haidong Shen, Eric A Sigel, Holly H Soutter, Nancy Su, Dawn M Troast, Haiyun Wang, Kate F Wickson, Chengyan Wu, Ying Zhang, Qiuying Zhao, Xiaolan Zheng, Alexander W Hird
Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 μM Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a β-turn conformation, such that the two ends of the peptide were close together...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28196749/recent-insights-into-the-molecular-mechanisms-underlying-pyroptosis-and-gasdermin-family-functions
#6
REVIEW
Robin A Aglietti, Erin C Dueber
Pyroptosis is an inflammatory form of cell death that not only protects multicellular organisms from invading pathogenic bacteria and microbial infections, but can also lead to sepsis and lethal septic shock if overactivated. Here, we present an overview of recent developments within the pyroptosis field, beginning with the discovery of Gasdermin D (GSDMD) as a substrate of caspase-1 and caspase-11 upon detection of cytosolic lipopolysaccharide (LPS). Cleavage releases the N-terminal domain of GSDMD, causing it to form cytotoxic pores in the plasma membrane of cells...
February 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28192510/downregulation-of-sp1-by-minnelide-leads-to-decrease-in-hsp70-and-decrease-in-tumor-burden-of-gastric-cancer
#7
Nivedita Arora, Osama Alsaied, Patricia Dauer, Kaustav Majumder, Shrey Modi, Bhuwan Giri, Vikas Dudeja, Sulagna Banerjee, Daniel Von Hoff, Ashok Saluja
BACKGROUND: Gastric cancer is the third leading cause of cancer related mortality worldwide with poor survival rates. Even though a number of chemotherapeutic compounds have been used against this disease, stomach cancer has not been particularly sensitive to these drugs. In this study we have evaluated the effect of triptolide, a naturally derived diterpene triepoxide and its water soluble pro-drug Minnelide on several gastric adenocarcinoma cell lines both as monotherapy and in combination with CPT-11...
2017: PloS One
https://www.readbyqxmd.com/read/28184331/verticillin-a-inhibits-leiomyosarcoma-and-malignant-peripheral-nerve-sheath-tumor-growth-via-induction-of-apoptosis
#8
A Zewdu, G Lopez, D Braggio, C Kenny, D Constantino, H K Bid, K Batte, O H Iwenofu, N H Oberlies, C J Pearce, A M Strohecker, D Lev, R E Pollock
OBJECTIVE: The heterogeneity of soft tissue sarcoma (STS) represents a major challenge for the development of effective therapeutics. Comprised of over 50 different histology subtypes of various etiologies, STS subsets are further characterized as either karyotypically simple or complex. Due to the number of genetic anomalies associated with genetically complex STS, development of therapies demonstrating potency against this STS cluster is especially challenging and yet greatly needed...
November 2016: Clinical & Experimental Pharmacology
https://www.readbyqxmd.com/read/28167474/regulatory-effect-of-caspase-11-on-interleukin-1%C3%AE-in-the-fungal-keratitis
#9
Keke Zhu, Hongmei Mu, Baimu Pi
Caused by fungus, fungal keratitis is a kind of infections corneal disease with high rate of blindness, which patients are mainly farmers in developing countries. Interleukin, as important proinflammatory cytokines, involve in immune defense process against fungal infection of cornea. The expression of interleukin in the pathogenesis of fungal keratitis, especially the main source of its cells, is not clear and the cell signaling pathways which regulate the synthesis and modification of interleukin is still unknown...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28161069/interleukin-11-induces-preterm-birth-and-modulates-decidual-inflammasome-gene-expression-in-mice
#10
Amy Winship, Evdokia Dimitriadis
Decidual inflammation and inflammasome activation contribute to the pathogenesis of preterm birth (PTB). Interleukin-(IL)11 exerts complex regulatory effects on inflammation and IL-11 protein is elevated in PTB decidua. We aimed to determine a functional role for IL-11 in parturition or PTB. IL-11 administration during middle-late gestation pregnancy induced preterm birth in 87.5% of mice versus saline controls. Litters from IL-11-treated mothers had reduced offspring weight and numbers of live pups. IL-11 up-regulated decidual gene expression of key components of the inflammasome including IL-1β, Caspase-1 and ASC...
February 2017: Placenta
https://www.readbyqxmd.com/read/28129885/renoprotective-chemical-constituents-from-an-edible-mushroom-pleurotus-cornucopiae-in-cisplatin-induced-nephrotoxicity
#11
Seoung Rak Lee, Dahae Lee, Hae-Jeung Lee, Hyung Jun Noh, Kiwon Jung, Ki Sung Kang, Ki Hyun Kim
Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12)...
January 19, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28117938/non-canonical-inflammasomes-antimicrobial-defense-that-doesn-t-play-by-the-rules
#12
REVIEW
Shauna M Crowley, Bruce A Vallance, Leigh A Knodler
While much research has focused on defining the actions of caspase-1 containing canonical inflammasomes in promoting host defense, non-canonical inflammasomes have received comparatively little attention. Exciting new concepts have recently emerged detailing their atypical mechanism of activation, importance in defending against cytosolic Gram-negative pathogens and role in innate immune defenses of non-myeloid cells, which has revamped interest in the study of non-canonical inflammmasomes. Here we will discuss these latest findings about caspase-4, -5 and -11 containing inflammasomes in the context of their role in pathogen elimination in mice and humans...
January 24, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28116423/-roles-of-curcumin-combined-with-paclitaxel-on-growth-inhibition-and-apoptosis-of-oral-squamous-cell-carcinoma-cell-line-cal27-in-vitro
#13
Min Liu, Jun Zhang, Jun-Fu Li, Xu-Xia Wang
PURPOSE: To investigate the effects of curcumin and paclitaxel on proliferation and apoptosis of human oral squamous carcinoma cell line CAL27. METHODS: CAL27 cells were cultured and treated with different concentrations of curcumin and paclitaxel separately or in combination for 24, 48 and 72 h. The cell proliferation was evaluated by MTT assay, and cell apoptosis was detected by Tunel staining. Expression of Bcl-2, Bax, and active caspase-3 were analyzed by Western blot...
October 2016: Shanghai Kou Qiang Yi Xue, Shanghai Journal of Stomatology
https://www.readbyqxmd.com/read/28110393/nitric-oxide-production-in-the-striatum-and-cerebellum-of-a-rat-model-of-preterm-global-perinatal-asphyxia
#14
M Barkhuizen, W D J Van de Berg, J De Vente, C E Blanco, A W D Gavilanes, H W M Steinbusch
Encephalopathy due to perinatal asphyxia (PA) is a major cause of neonatal morbidity and mortality in the period around birth. Preterm infants are especially at risk for cognitive, attention and motor impairments. Therapy for this subgroup is limited to supportive care, and new targets are thus urgently needed. Post-asphyxic excitotoxicity is partially mediated by excessive nitric oxide (NO) release. The aims of this study were to determine the timing and distribution of nitric oxide (NO) production after global PA in brain areas involved in motor regulation and coordination...
January 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28109721/inflammasome-priming-in-sterile-inflammatory-disease
#15
REVIEW
Meghana N Patel, Richard G Carroll, Silvia Galván-Peña, Evanna L Mills, Robin Olden, Martha Triantafilou, Amaya I Wolf, Clare E Bryant, Kathy Triantafilou, Seth L Masters
The inflammasome is a cytoplasmic protein complex that processes interleukins (IL)-1β and IL-18, and drives a form of cell death known as pyroptosis. Oligomerization of this complex is actually the second step of activation, and a priming step must occur first. This involves transcriptional upregulation of pro-IL-1β, inflammasome sensor NLRP3, or the non-canonical inflammasome sensor caspase-11. An additional aspect of priming is the post-translational modification of particular inflammasome constituents...
January 18, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28108625/combined-parthenolide-and-balsalazide-have-enhanced-antitumor-efficacy-through-blockade-of-nf-%C3%AE%C2%BAb-activation
#16
Se-Lim Kim, Seong Hun Kim, Young Ran Park, Yu-Chuan Liu, Eun-Mi Kim, Hwan-Jeong Jeong, Yo Na Kim, Seung Young Seo, In Hee Kim, Seung Ok Lee, Soo Teik Lee, Sang-Wook Kim
: Balsalazide is a colon-specific prodrug of 5-aminosalicylate that is associated with a reduced risk of colon cancer in patients with ulcerative colitis. Parthenolide, a strong NF-κB inhibitor, has recently been demonstrated to be a promising therapeutic agent, promoting apoptosis of cancer cells. In the current study, the antitumor effect of balsalazide combined with parthenolide in human colorectal cancer cells and colitis-associated colon cancers (CAC) was investigated. The results demonstrate that the combination of balsalazide and parthenolide markedly suppress proliferation, nuclear translocation of NF-κB, IκB-α phosphorylation, NF-κB DNA binding, and expression of NF-κB targets...
November 14, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28071583/anticancer-activities-of-new-n-hetaryl-2-cyanoacetamide-derivatives-incorporating-4-5-6-7-tetrahydrobenzo-b-thiophene-moiety
#17
Magda F Mohamed, Yasmin M Attia, Samia A Shouman, Ismail A Abdelhamid
Novel series of N-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives are synthesized. The structure of these compounds was elucidated using different spectral tools. Compounds were evaluated for their cytotoxic activities against different types of human cancer cell lines including, breast (MCF-7, T47D, MDA MB231); liver (HEPG-2); colon (HCT116); prostate (PC3); and cervix (HELA) cells. In this study, we used compounds 11 and 12 that showed the highest cytotoxicity on PC3 and HEPG2 cells, to explore their effects on apoptosis, invasion ampamp; metastasis and angiogenesis...
January 10, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28067534/molecular-cloning-alternative-splicing-and-mrna-expression-analysis-of-magi1-and-its-correlation-with-laying-performance-in-geese
#18
S Yu, M Xia, M A Alsiddig, H Liu, W Wei, J Chen
1. In a previous study, a laying-related single nucleotide polymorphism (SNP) Record-106975 (A-G) was found in the intron of Membrane-associated Guanylate Kinase with Inverted Domain Structure-1 gene (MAGI1) by restriction site-associated DNA sequencing. This study was performed to further identify the function of MAGI1 on laying performance in Yangzhou geese. 2. The complete MAGI1 cDNA sequence was cloned from the ovary of the Yangzhou goose. A total of 4 alternative splice variants were identified, and the characterisation of their nucleic acid and amino acid sequences were analysed...
January 9, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28032341/nlrp3-inflammasome-mediates-il-1%C3%AE-production-in-immune-cells-in-response-to-acinetobacter-baumannii-and-contributes-to-pulmonary-inflammation-in-mice
#19
Min-Jung Kang, Sung-Gang Jo, Dong-Jae Kim, Jong-Hwan Park
Acinetobacter baumannii is a multi-drug resistant gram-negative bacteria, and infection with this organism is one of the major causes of mortality in intensive care units. Inflammasomes are multiprotein oligomers that include caspase-1, and their activation is required for maturation of IL-1β. Inflammasome signaling is involved in host defenses against various microbial infection, but the precise mechanism by which A. baumannii activates inflammasomes and the roles of relevant signals in host defense against pulmonary A...
December 29, 2016: Immunology
https://www.readbyqxmd.com/read/28027901/fungicide-bac8c-triggers-attenuation-of-mitochondrial-homeostasis-and-caspase-dependent-apoptotic-death
#20
Heejeong Lee, Dong Gun Lee
Bac8c (RIWVIWRR-NH2), an 8-mer peptide modified from amino acids 4-11 of Bac2a, shows broad-spectrum activity against pathogenic bacteria and yeast, and it has been the focus of attention owing to its low cost of synthesis. Although Bac8c is effective against Candida albicans, its mode of action needs to be investigated further. Bac8c causes yeast cell death in a dose-dependent manner by eliciting the production of reactive oxygen species, thereby attenuating the antioxidant defense system. It is also involved in Ca(2+) signaling, and produces apoptotic features, such as phosphatidylserine externalization and DNA fragmentation...
February 2017: Biochimie
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