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https://www.readbyqxmd.com/read/28550810/rigid-aromatic-linking-moiety-in-cationic-lipids-for-enhanced-gene-transfection-efficiency
#1
Bing Wang, Rui-Mo Zhao, Ji Zhang, Yan-Hong Liu, Zheng Huang, Qing-Ying Yu, Xiao-Qi Yu
Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines...
May 17, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28550769/mk-8776-a-novel-chk1-inhibitor-exhibits-an-improved-radiosensitizing-effect-compared-to-ucn-01-by-exacerbating-radiation-induced-aberrant-mitosis
#2
Motofumi Suzuki, Tohru Yamamori, Tomoki Bo, Yuri Sakai, Osamu Inanami
Checkpoint kinase 1 (Chk1) is an evolutionarily conserved serine/threonine kinase that plays an important role in G2/M checkpoint signaling. Here, we evaluate the radiosensitizing effects of a novel selective Chk1 inhibitor MK-8776, comparing its efficacy with a first-generation Chk1 inhibitor UCN-01, and attempt to elucidate the mechanism of radiosensitization. In a clonogenic survival assay, MK-8776 demonstrated a more pronounced radiosensitizing effect than UCN-01, with lower cytotoxicity. Importantly, radiosensitization by MK-8776 can be achieved at doses as low as 2...
May 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28550753/catalase-loaded-cisplatin-prodrug-constructed-liposomes-to-overcome-tumor-hypoxia-for-enhanced-chemo-radiotherapy-of-cancer
#3
Rui Zhang, Xuejiao Song, Chao Liang, Xuan Yi, Guosheng Song, Yu Chao, Yu Yang, Kai Yang, Liangzhu Feng, Zhuang Liu
Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28550296/reducing-mitochondrial-reads-in-atac-seq-using-crispr-cas9
#4
Lindsey Montefiori, Liana Hernandez, Zijie Zhang, Yoav Gilad, Carole Ober, Gregory Crawford, Marcelo Nobrega, Noboru Jo Sakabe
ATAC-seq is a high-throughput sequencing technique that identifies open chromatin. Depending on the cell type, ATAC-seq samples may contain ~20-80% of mitochondrial sequencing reads. As the regions of open chromatin of interest are usually located in the nuclear genome, mitochondrial reads are typically discarded from the analysis. We tested two approaches to decrease wasted sequencing in ATAC-seq libraries generated from lymphoblastoid cell lines: targeted cleavage of mitochondrial DNA fragments using CRISPR technology and removal of detergent from the cell lysis buffer...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550099/viral-delivery-of-c9orf72-hexanucleotide-repeat-expansions-in-mice-lead-to-repeat-length-dependent-neuropathology-and-behavioral-deficits
#5
Saul Herranz-Martin, Jayanth Chandran, Katherine Lewis, Padraig Mulcahy, Adrian Higginbottom, Callum Walker, Isabel Martinez-Pena Y Valenzuela, Ross A Jones, Ian Coldicott, Tommaso Iannitti, Mohammed Akaaboune, Sherif F El-Khamisy, Thomas H Gillingwater, Pamela J Shaw, Mimoun Azzouz
Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two major pathologies stemming from the hexanucleotide RNA expansions (HREs) have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN) dipeptides, though it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here we generated two novel lines of mice that overexpress either 10 pure or 102 interrupted G4C2 repeats mediated by adeno-associated virus (AAV) and characterized relevant pathology and disease-related behavioral phenotypes...
May 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28550049/recovery-of-ethanol-induced-akkermansia-muciniphila-depletion-ameliorates-alcoholic-liver-disease
#6
Christoph Grander, Timon E Adolph, Verena Wieser, Patrick Lowe, Laura Wrzosek, Benedek Gyongyosi, Doyle V Ward, Felix Grabherr, Romana R Gerner, Alexandra Pfister, Barbara Enrich, Dragos Ciocan, Sophie Macheiner, Lisa Mayr, Matthias Drach, Patrizia Moser, Alexander R Moschen, Gabriel Perlemuter, Gyongyi Szabo, Anne Marie Cassard, Herbert Tilg
OBJECTIVE: Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. Akkermansia muciniphila, a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of A. muciniphila administration on the course of ALD. DESIGN: The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal A...
May 26, 2017: Gut
https://www.readbyqxmd.com/read/28549377/biocompatibility-of-liposome-nanocarriers-in-the-rat-inner-ear-after-intratympanic-administration
#7
Jing Zou, Hao Feng, Rohit Sood, Paavo K J Kinnunen, Ilmari Pyykko
Liposome nanocarriers (LPNs) are potentially the future of inner ear therapy due to their high drug loading capacity and efficient uptake in the inner ear after a minimally invasive intratympanic administration. However, information on the biocompatibility of LPNs in the inner ear is lacking. The aim of the present study is to document the biocompatibility of LPNs in the inner ear after intratympanic delivery. LPNs with or without gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) were delivered to the rats through transtympanic injection...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28548949/dietary-grape-seed-proanthocyanidins-inactivate-regulatory-t-cells-by-promoting-ner-dependent-dna-repair-in-dendritic-cells-in-uvb-exposed-skin
#8
Mudit Vaid, Ram Prasad, Tripti Singh, Santosh K Katiyar
Ultraviolet B (UVB) radiation induces regulatory T cells (Treg cells) and depletion of these Treg cells alleviates immunosuppression and inhibits photocarcinogenesis in mice. Here, we determined the effects of dietary grape seed proanthocyanidins (GSPs) on the development and activity of UVB-induced Treg cells. C3H/HeN mice fed a GSPs (0.5%, w/w)-supplemented or control diet were exposed to UVB (150 mJ/cm2) radiation, sensitized to 2,4-dinitrofluorobenzene (DNFB) and sacrificed 5 days later. FACS analysis indicated that dietary GSPs decrease the numbers of UVB-induced Treg cells...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#9
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548877/role-of-osgin1-in-mediating-smoking-induced-autophagy-in-the-human-airway-epithelium
#10
Guoqing Wang, Haixia Zhou, Yael Strulovici-Barel, Mohammed Al-Hijji, Xuemei Ou, Jacqueline Salit, Matthew S Walters, Michelle R Staudt, Robert J Kaner, Ronald G Crystal
Enhanced macroautophagy/autophagy is recognized as a component of the pathogenesis of smoking-induced airway disease. Based on the knowledge that enhanced autophagy is linked to oxidative stress and the DNA damage response, both of which are linked to smoking, we used microarray analysis of the airway epithelium to identify smoking upregulated genes known to respond to oxidative stress and the DNA damage response. This analysis identified OSGIN1 (oxidative stress induced growth inhibitor 1) as significantly upregulated by smoking, in both the large and small airway epithelium, an observation confirmed by an independent small airway microarray cohort, TaqMan PCR of large and small airway samples and RNA-Seq of small airway samples...
May 26, 2017: Autophagy
https://www.readbyqxmd.com/read/28548569/thyroxine-increases-collagen-type-ii-expression-and-accumulation-in-scaffold-free-tissue-engineered-articular-cartilage
#11
G Adam Whitney, Thomas J Kean, Russell J Fernandes, Stephen D Waldman, M Yat Tse, Stephen C Pang, Joseph M Mansour, James E Dennis
Low collagen accumulation in the extra-cellular matrix is a pressing problem in cartilage tissue engineering, leading to a low collagen-to-glycosaminoglycan (GAG) ratio and poor mechanical properties in neo-cartilage. Soluble factors have been shown to increase collagen content, but may result in a more pronounced increase in GAG content. Thyroid hormones have been reported to stimulate collagen and GAG production, but reported outcomes, including which specific collagen types are affected, are variable throughout the literature...
May 26, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28548177/specific-dna-sequences-allosterically-enhance-protein-protein-interaction-in-a-transcription-factor-through-modulation-of-protein-dynamics-implications-for-specificity-of-gene-regulation
#12
Abhishek Mazumder, Subrata Batabyal, Manas Mondal, Tanumoy Mondol, Susobhan Choudhury, Raka Ghosh, Tanaya Chatterjee, Dhananjay Bhattacharyya, Samir Kumar Pal, Siddhartha Roy
Most genes are regulated by multiple transcription factors, often assembling into multi-protein complexes in the gene regulatory region. Understanding of the molecular origin of specificity of gene regulatory complex formation in the context of the whole genome is currently inadequate. A phage transcription factor λ-CI forms repressive multi-protein complexes by binding to multiple binding sites in the genome to regulate the lifecycle of the phage. The protein-protein interaction between two DNA-bound λ-CI molecules is stronger when they are bound to the correct pair of binding sites, suggesting allosteric transmission of recognition of correct DNA sequences to the protein-protein interaction interface...
May 26, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28547133/hsf1-acetylation-decreases-its-transcriptional-activity-and-enhances-glucolipotoxicity-induced-apoptosis-in-rat-and-human-beta-cells
#13
Indri Purwana, Jun J Liu, Bernard Portha, Jean Buteau
AIMS/HYPOTHESIS: Heat shock factor protein 1 (HSF1) is a transcription factor that regulates the expression of key molecular chaperones, thereby orchestrating the cellular response to stress. This system was recently implicated in the control of insulin sensitivity and is therefore being scrutinised as a novel therapeutic avenue for type 2 diabetes. However, the regulation and biological actions of HSF1 in beta cells remain elusive. Herein, we sought to investigate the regulation of HSF1 in pancreatic beta cells and to study its potential role in cell survival...
May 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28547116/groove-binding-of-vanillin-and-ethyl-vanillin-to-calf-thymus-dna
#14
Kaixin Xia, Guowen Zhang, Song Li, Deming Gong
Vanillin (VAN) and ethyl vanillin (EVA) are widely used food additives as flavor enhancers, but may have a potential security risk. In this study, the properties of binding of VAN or EVA with calf thymus DNA (ctDNA) were characterized by multi-spectroscopic methods, multivariate curve resolution-alternating least-squares (MCR-ALS) algorithm and molecular simulation. The concentration profiles for the components (VAN or EVA, ctDNA and VAN-ctDNA or EVA-ctDNA complex) by the MCR-ALS analysis showed that VAN or EVA interacted with ctDNA and formed VAN-ctDNA or EVA-ctDNA complex...
May 25, 2017: Journal of Fluorescence
https://www.readbyqxmd.com/read/28546713/current-concepts-of-epigenetics-in-testicular-cancer
#15
REVIEW
Alfredo Harb-De la Rosa, Meenakkshy Manoharan, Ahmed Saeed Goolam
Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure...
June 2017: Indian Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28546518/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#16
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28546133/tissue-engineered-trachea-regeneration-using-decellularized-trachea-matrix-treated-with-laser-micropore-technique
#17
Yong Xu, Dan Li, Zongqi Yin, Aijuan He, Miaomiao Lin, Gening Jiang, Xiao Song, Xuefei Hu, Yi Liu, Jinpeng Wang, Xiaoyun Wang, Liang Duan, Guangdong Zhou
Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth...
May 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28545975/quinazolinone-derivatives-as-inhibitors-of-homologous-recombinase-rad51
#18
Ambber Ward, Lilong Dong, Jonathan M Harris, Kum Kum Khanna, Fares Al-Ejeh, David P Fairlie, Adrian P Wiegmans, Ligong Liu
RAD51 is a vital component of the homologous recombination DNA repair pathway and is overexpressed in drug-resistant cancers, including aggressive triple negative breast cancer (TNBC). A proposed strategy for improving therapeutic outcomes for patients is through small molecule inhibition of RAD51, thereby sensitizing tumor cells to DNA damaging irradiation and/or chemotherapy. Here we report structure-activity relationships for a library of quinazolinone derivatives. A novel RAD51 inhibitor (17) displays up to 15-fold enhanced inhibition of cell growth in a panel of TNBC cell lines compared to compound B02, and approximately 2-fold increased inhibition of irradiation-induced RAD51 foci formation...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28545672/enhancement-of-apoptotic-activities-on-brain-cancer-cells-via-the-combination-of-%C3%AE-tocotrienol-and-jerantinine-a
#19
Ibrahim Babangida Abubakar, Kuan-Hon Lim, Toh-Seok Kam, Hwei-San Loh
BACKGROUND: γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28545464/c10orf10-depp-mediated-ros-accumulation-is-a-critical-modulator-of-foxo3-induced-autophagy
#20
S Salcher, M Hermann, U Kiechl-Kohlendorfer, M J Ausserlechner, P Obexer
BACKGROUND: Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance. We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification...
May 25, 2017: Molecular Cancer
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