Search results for "Repair"

2020

Abstract One of the most abundant DNA lesions induced by oxidative stress is the highly mutagenic 8-oxoguanine (8-oxoG), which is specifically recognized by 8-oxoguanine DNA glycosylase 1 (OGG1) to initiate its repair. How DNA glycosylases find small non-helix-distorting DNA lesions amongst millions of bases packaged in the chromatin-based architecture of the genome remains an open question. Here, we used a high-throughput siRNA screening to identify factors involved in the recognition of 8-oxoG by OGG1. We show that cohesin and mediator subunits are required for re-localization of OGG1 and other base excision repair factors to chromatin upon oxidative stress. The association of OGG1 with e…

The sharedneoantigen landscape of MSI cancers reflects immunoediting during tumor evolution

2019

AbstractThe immune system can recognize and attack cancer cells, especially those with a high load of mutation-inducedneoantigens. Suchneoantigens are particularly abundant in DNA mismatch repair (MMR)-deficient, microsatellite-unstable (MSI) cancers. MMR deficiency leads to insertion/deletion (indel) mutations at coding microsatellites (cMS) and toneoantigen-inducing translational frameshifts. The abundance of mutationalneoantigens renders MSI cancers sensitive to immune checkpoint blockade. However, the neoantigen landscape of MMR-deficient cancers has not yet been systematically mapped. In the present study, we used a novel tool to monitorneoantigen-inducing indel mutations in MSI colore…

Flipping of alkylated DNA damage bridges base and nucleotide excision repair

2009

Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer chemotherapy target O6-alkylguanine-DNA alkyltransferase (AGT) and paradoxically protect cells from the biological effects of DNA alkylation damage, despite lacking the reactive cysteine and alkyltransferase activity of AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with damaged DNA containing the endogenous lesion O6-methylguanine or cigarette-smoke-derived O6-4-(3-pyridyl)-4-oxobutylguanine. These results reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and binding pocket size compared to AGT. Our analysis of lesion-binding site conservation identifies new A…

Nanodesign of new self-assembling core-shell gellan-transfersomes loading baicalin and in vivo evaluation of repair response in skin

2017

Gellan nanohydrogel and phospholipid vesicles were combined to incorporate baicalin in new self-assembling core-shell gellan-transfersomes obtained by an easy, scalable method. The vesicles were small in size (~107 nm) and monodispersed (P.I. ≤ 0.24), forming a viscous system (~24 mPa/s) as compared to transfersomes (~1.6 mPa/s), as confirmed by rheological studies. Gellan was anchored to the bilayer domains through cholesterol, and the polymer chains were distributed onto the outer surface of the bilayer, thus forming a core-shell structure, as suggested by SAXS analyses. The optimal carrier ability of core-shell gellan-transfersomes was established by the high deposition of baicalin in th…

In Vivo Reprogramming for Brain and Spinal Cord Repair.

2015

AbstractCell reprogramming technologies have enabled the generation of various specific cell types including neurons from readily accessible patient cells, such as skin fibroblasts, providing an intriguing novel cell source for autologous cell transplantation. However, cell transplantation faces several difficult hurdles such as cell production and purification, long-term survival, and functional integration after transplantation. Recently,in vivoreprogramming, which makes use of endogenous cells for regeneration purpose, emerged as a new approach to circumvent cell transplantation. There has been evidence forin vivoreprogramming in the mouse pancreas, heart, and brain and spinal cord with …

Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells

2015

Abstract Background Cancer is a complex disease with multiple genetic and epigenetic alterations. Since decades, the hallmark of cancer therapy is chemotherapy. Cytotoxic drugs erase rapidly dividing cells without sufficient differentiation between normal and cancerous cells resulting in severe side effects in normal tissues. Recently, strategies for cancer treatment focused on targeting specific proteins involved in tumor growth and progression. The present study was designed to investigate the cytotoxicity of 65 crude extracts from 35 Sudanese medicinal plants towards various cancer cell lines expressing molecular mechanisms of resistance towards classical chemotherapeutics (two ATP-bindi…

Abdominal Compartment Syndrome (ACS) After Surgical Abdominal Aortic Aneurysm (AAA) Repair

2009

Hypotensive Hemostasis in Patients Presenting with Ruptured Aortic Aneurysm

2017

Hypotensive hemostasis in aortic rupture has been showed to be feasible and advantageous, especially in trauma patients. To date, there are no randomized studies on hypotensive hemostasis in patients with ruptured abdominal aortic aneurysm (rAAA), but observational studies indicate similar advantages when hypotensive hemostasis is used for endovascular aneurysm repair (EVAR) as in trauma patients. Actually, in EVAR for rAAA, a target systolic blood pressure of 90 mmHg or even lower is considered safe in conscious patients. Fluids should be administrated judiciously with the sole aim of maintaining adequate cardiac output and tissue oxygenation, whereas vasoactive pressors or dilatators may …

Achilles tendon rupture: percutaneous repairing

2011

Active repair technology applied to delaminated composite structures

2009

The main target of the present paper is represented by the fracture mechanics charac-terization of delaminated composite structures actively repaired through piezoelectric patches. A boundary element code, formulated for anisotropic piezoelectric solids, including, as limiting case, the applicability to linear elastic anisotropic materials has been then imple-mented. The modeling of the delaminated composite structures as well as of the assembled structures, made of the damaged components and the patches, has been achieved through the multidomain technique. Moreover, to take into account for the adhesive layer between the host structures and the piezoelectric patches, a "spring-model" has b…