Carrier multiplication between interacting nanocrystals for fostering silicon-based photovoltaics

Being a source of clean and renewable energy, the possibility to convert solar radiation in electric current with high efficiency is one of the most important topics of modern scientific research. Currently the exploitation of interaction between nanocrystals seems to be a promising route to foster the establishment of third generation photovoltaics. Here we adopt a fully ab-initio scheme to estimate the role of nanoparticle interplay on the carrier multiplication dynamics of interacting silicon nanocrystals. Energy and charge transfer-based carrier multiplication events are studied as a function of nanocrystal separation showing benefits induced by the wavefunction sharing regime. We prove the relevance of these recombinative mechanisms for photovoltaic applications in the case of silicon nanocrystals arranged in dense arrays, quantifying at an atomistic scale which conditions maximize the outcome.Comment: Supplementary materials are freely available onlin

Drug-DNA interaction protocols

In a paper published by Jurgen Drews on the march 17, 2000 issue of Science a figure reporting molecular targets of drug therapy, classified according to biochemical criteria, showed that only 2% of drugs were directed to DNA. Presently, the number of DNA targeting molecules, primarily for Cancer treatment, is increasing along with the number of applications in medicine. The design of such molecules relies on the quantitative assessment of the binding strength of small molecules to DNA. For this purpose various techniques suitable to work in the subnanomolar range have been developed.....

Targeting dementias through cancer kinases inhibition

The failures in Alzheimer's disease (AD) therapy strongly suggest the importance of reconsidering the research strategies analyzing other mechanisms that may take place in AD as well as, in general, in other neurodegenerative dementias. Taking into account that in AD a variety of defects result in neurotransmitter activity and signaling efficiency imbalance, neuronal cell degeneration and defects in damage/repair systems, aberrant and abortive cell cycle, glial dysfunction, and neuroinflammation, a target may be represented by the intracellular signaling machinery provided by the kinome. In particular, based on the observations of a relationship between cancer and AD, we focused on cancer kinases for targeting neurodegeneration, highlighting the importance of targeting the intracellular pathways at the intersection between cell metabolism control/duplication, the inhibition of which may stop a progression in neurodegeneration

Lactate Upregulates the Expression of DNA Repair Genes, Causing Intrinsic Resistance of Cancer Cells to Cisplatin

Intrinsic or acquired drug resistance is one of the major problems compromising the success of antineoplastic treatments. Several evidences correlated some therapeutic failures with changes in cell metabolic asset and in line with these findings, hindering the glycolytic metabolism of cancer cells via lactate dehydrogenase (LDH) inhibition was found to overcome the resistance to chemotherapeutic agents. Lactate, the product of LDH reaction, was shown to be involved in epigenetic regulation of gene expression. The experiments described in this paper were aimed at highlighting a possible direct effect of lactate in modifying the response of cancer cells to a chemotherapeutic treatment. To discriminate between the effects potentially caused by glycolytic metabolism from those directly referable to lactate, we selected cancer cell lines able to grow in glucose deprived conditions and evaluated the impact of lactate on the cellular response to cisplatin-induced DNA damage. In lactate-exposed cells we observed a reduced efficacy of cisplatin, which was associated with reduced signatures of DNA damage, enhanced DNA recombination competence and increased expression of a panel of genes involved in DNA repair. The identified genes take part in mismatch and nucleotide excision repair pathways, which were found to contribute in restoring the cisplatin-induced DNA damage. The obtained results suggest that this metabolite could play a role in reducing the efficacy of antineoplastic treatments

insights into the definition of terms in european medical device regulation

ABSTRACTIntroduction: Medical devices comprise apparatus/instruments, software, and materials with therapeutic activities obtained by principal mechanisms of action different from pharmacological, immunological and metabolic, which are proper of medicinal products. In this context the key for the distinction between medicinal products and devices lies in the correct interpretation of these terms, which, although defined in a guideline, are still not univocally interpreted.Areas covered: This article discusses the definitions of pharmacological and non-pharmacological mechanisms of action, such as the chemical and physical means. The aim is to give insights on the correct definition these terms in order to contribute to build the desired synergy between scientific and regulatory fields and promote a correct interpretation of the European regulatory framework as well as sustainable health and innovation.Expert commentary: We propose a series of definitions and a method to interpret those definitions within ..

Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?

p53 transcriptional activity depends mainly on posttranslational modifications and protein/protein interaction. Another important mechanism that controls p53 function is its conformational stability since p53 is an intrinsically unstable protein. An altered conformational state of p53, independent from point mutations, has been reported in tissues from patients with Alzheimer's disease (AD), leading to an impaired and dysfunctional response to stressors. Recent evidence shows that one of the activators that induces p53 posttranslational modification and wild-type conformational stability is homeodomain interacting protein kinase 2 (HIPK2). Hence, conditions that induce HIPK2 deregulation would result in a dysfunctional response to stressors by affecting p53 activity. Discovering the mechanisms of HIPK2 activation/inhibition and the ways to manipulate HIPK2 activity are an interesting option to affect several biological pathways, including those underlying AD. Soluble beta-amyloid peptides have recently been involved in HIPK2 degradation, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus, before triggering the amyloidogenic cascade. Here we discuss about these findings and the potential relevance of HIPK2 as a target for AD and highlight the existence of a novel amyloid-based mechanism in AD potentially leading to the survival of injured dysfunctional cells

The activation of lactate dehydrogenase induced by mTOR drives neoplastic change in breast epithelial cells

mTOR kinase and the A isoform of lactate dehydrogenase (LDH-A) are key players controlling the metabolic characteristics of cancer cells. By using cultured human breast cells as a \u201cmetabolic tumor\u201d model, we attempted to explore the correlation between these two factors. \u201cMetabolic tumors\u201d are defined as neoplastic conditions frequently associated with features of the metabolic syndrome, such as hyper-insulinemia and hyper-glycemia. MCF-7 cells (a well differentiated carcinoma) and MCF-10A cells (a widely used model for studying normal breast cell transformation) were used in this study. These cells were exposed to known factors triggering mTOR activation. In both treated cultures, we evaluated the link between mTOR kinase activity and the level of LDH expression / function. Furthermore, we elaborated the metabolic changes produced in cells by the mTOR-directed LDH-A up-regulation. Interestingly, we observed that in the non-neoplastic MCF-10A culture, mTOR-directed up-regulation of LDH-A was followed by a reprogramming of cell metabolism, which showed an increased dependence on glycolysis rather than on oxidative reactions. As a consequence, lactate production appeared to be enhanced and cells began to display increased self-renewal and clonogenic power: signals suggestive of neoplastic change. Enhanced clono-genicity of cells was abolished by rapamycin treatment, and furthermore heavily reduced by LDH enzymatic inhibition. These results highlighted a mechanistic link between metabolic alterations and tumorigenesis, whereby suggesting LDH inhibition as a possible chemo-preventive measure to target the metabolic alterations driving neoplastic change

LDH inhibition impacts on heat shock response and induces senescence of hepatocellular carcinoma cells

In normal cells, heat shock response (HSR) is rapidly induced in response to a variety of harmful conditions and represents one of the most efficient defense mechanism. In cancer tissues, constitutive activation converts HSR into a life-threatening process, which plays a major role in helping cell survival and proliferation. Overexpression of heat shock proteins (HSPs) has been widely reported in human cancers and was found to correlate with tumor progression. Hepatocellular carcinoma is one of the conditions in which HSR activation was shown to have the highest clinical significance. Transcription of HSPs is induced by HSF-1, which also activates glycolytic metabolism and increases the expression of LDH-A, the master regulator of the Warburg effect. In this paper, we tried to explore the relationship between HSR and LDH-A. In cultured hepatocellular carcinoma cells, by using two enzyme inhibitors (oxamate and galloflavin), we found that the reduction of LDH-A activity led to decreased level and function of the major HSPs involved in tumorigenesis. Galloflavin (a polyphenol) also inhibited the ATPase activity of two of the examined HSPs. Finally, hindering HSR markedly lowered the alpha-fetoprotein cellular levels and induced senescence. Specific inhibitors of single HSPs are currently under evaluation in different neoplastic diseases. However, one of the effects usually observed during treatment is a compensatory elevation of other HSPs, which decreases treatment efficacy. Our results highlight a connection between LDH and HSR and suggest LDH inhibition as a way to globally impact on this tumor promoting process

Hyaluronic acid enhance polynucleotides effect on cultured dermal fibroblasts

Polynucleotides (PNs) and Hyaluronic Acid (HA) are compounds widely used to promote tissue regeneration, mainly in cutis and cartilage. PNs efficacy has been demonstrated in vitro on cultured dermal fibroblasts and osteoblasts, and in animal models where it has been demonstrated to increase dermal regeneration. PNs effects are mediated mainly through the activation of P2P purinergic receptors, which are expressed on fibroblasts and on mesenchymal-derived cells. HA, the most abundant and non solphorate glycosaminoglycan (GAG) produced by fibroblasts, is envolved in several biological effects which are different in response of the sizes of HA molecules. When used as non fragmented, (about 2 Kd) HA has both an anti-inflammatory and antiapoptotic effects and it stimulates cell migration. In this study we have analyzed the effect of a mixture of PNs and HA, in order to verify a possible synergic effect, on human dermal fibroblasts. Effects on cell proliferation were evaluated with MTT assay and cell culture protein content. Dose-response curves showed higher effects on cell proliferation when PNs were used in the presence of HA. In particular we observed that, the addiction of HA determined a peak of activity with a reduction of of about a third of PNs dose. These preliminary data are suggesting for a joint use of HA and PN in tissue regeneration, mainly in clinical situation, like for example cutaneous burn in with the presence of PN induce a more rapid regeneration by means of more rapid cell ingrowth, collagen and VEGF production. At the same time HA support cell migration and contribute to reduce inflammatory processes