Nanomedicine: Photo-activated nanostructured titanium dioxide, as a promising anticancer agent.

The multivariate condition of cancer disease has been approached in various ways, by the scientific community. Recent studies focus on individualized treatments, minimizing the undesirable consequences of the conventional methods, but the development of an alternative effective therapeutic scheme remains to be held. Nanomedicine could provide a solution, filling this gap, exploiting the unique properties of innovative nanostructured materials. Nanostructured titanium dioxide (TiO2) has a variety of applications of daily routine and of advanced technology. Due to its biocompatibility, it has also a great number of biomedical applications. It is now clear that photo-excited TiO2 nanoparticles, induce generation of pairs of electrons and holes which react with water and oxygen to yield reactive oxygen species (ROS) that have been proven to damage cancer cells, triggering controlled cellular processes. The aim of this review is to provide insights into the field of nanomedicine and particularly into the wide context of TiO2-NP-mediated anticancer effect, shedding light on the achievements of nanotechnology and proposing this nanostructured material as a promising anticancer photosensitizer.

Antibody-mediated rejection with the presence of glomerular crescents in a pediatric kidney transplant recipient: A case report.

Glomerular crescents in kidney transplantation are indicative of severe glomerular injury and constitute a hallmark of RPGN. Their concurrence with ABMR has been rarely described only in adult patients. We report a case of 10-year-old boy with compound heterozygous Fin-major Finnish-type congenital nephrotic syndrome, who had received a deceased-donor kidney transplant 5 years before onset of acute kidney injury and nephrotic range proteinuria without hematuria. Kidney allograft biopsy illustrated 6 glomeruli with global sclerosis and 6 with remarkable circumferential or segmental cellular crescents. Negative glomerular immunofluorescence for immune-complex deposits and the absence of serum ANCA eliminated the presence of immune-mediated and ANCA-positive pauci-immune crescentic glomerulonephritis. Diagnosis of ABMR was based on the high levels of HLA class II DSA and the histological evidence of glomerulitis, peritubular capillaritis, and acute tubular injury with positive linear peritubular capillary C4d staining. The patient despite plasmapheresis and enhanced immunosuppressive treatment progressed to end-stage renal disease. We conclude that glomerular crescents may represent a finding of AMBR and possibly a marker of poor allograft prognosis in pediatric patients.

Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing.

The cyclin-dependent kinase inhibitor p21(WAF1/CIP1) (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4-CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery-an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs.

Apoptosis or senescence? Which exit route do epithelial cells and fibroblasts preferentially follow?

Senescence and apoptosis constitute types of cellular responses that normally ensure homeostasis, when endogenous or exogenous signals occur. Their deregulation is often observed in various pathologies, such as age and non-age related diseases including cancer. Although epithelial cells and fibroblasts are capable to exert both functions, under a plethora of insults, the fact that they exhibit notable intrinsic differences in cell/tissue homeostasis properties, might be a crucial determinant of the mode of response to a certain stress signal. Sparse evidence in the literature reveals that in the same tissue/organ context and under the same conditions, the cell type seems to drive the differential counteraction between epithelia and fibroblasts. Based on the above notion we propose that, upon stress insults, human fibroblasts seem to predominantly respond via senescence, while epithelial cells prefer to exert apoptosis. We suggest that considering the tissue as a whole (epithelium and stroma) would benefit research into new therapeutic strategies for chronic diseases and cancer.

Modulation of hepatic microsomal triglyceride transfer protein (MTP) induced by S-nitroso-N-acetylcysteine in ob/ob mice.

We evaluated the effects of a potent NO donor, S-nitroso-N-acetylcysteine (SNAC), on microsomal triglyceride transfer protein (MTP) expression in ob/ob mice. NAFLD was induced in male ob/ob mice using a methionine-choline deficient diet (MCD) concomitantly with oral SNAC fed solution (n=5) or vehicle (control; n=5) by gavage daily for 4 weeks. Livers were collected for histology and for assessing MTP by RT-qPCR, Western blot, immunohistochemistry and immunogold electron microscopy analyses. Histological analysis showed diffuse macro and microvesicular steatosis, moderate hepatocellular ballooning and moderate inflammatory infiltrate in ob/ob mice fed the MCD diet. With SNAC, mice showed a marked reduction in liver steatosis (p<0.01), in parenchymal inflammation (p=0.02) and in MTP protein immunoexpression in zone III (p=0.05). Moreover, SNAC caused reduction of MTP protein in Western blot analysis (p<0.05). In contrast, MTP mRNA content was significantly higher (p<0.05) in mice receiving SNAC. Immuno-electron microscopy showed MTP localized in the rough endoplasmic reticulum of hepatocytes in both treated and untreated groups. However with SNAC treatment, MTP was also observed surrounding fat globules. Histological improvement mediated by a nitric oxide donor is associated with significantly altered expression and distribution of MTP in this animal model of fatty liver disease. Further studies are in progress to examine possible mechanisms and to develop SNAC as a possible therapy for human fatty liver disease.