1,722,115 research outputs found
La mosaïque romaine de Cirone (Espagne)
No full textLaurière Jules de. La mosaïque romaine de Cirone (Espagne). In: Bulletin Monumental, tome 53, année 1887. pp. 235-251
ZnCl2 sustains the adriamycin-induced cell death inhibited by high glucose
No full textHyperglycemia, the condition of high blood glucose, is typical of diabetes and obesity and represents a significant clinical problem. The relationship between hyperglycemia and cancer risk has been established by several studies. Moreover, hyperglycemia has been shown to reduce cancer cell response to therapies, conferring resistance to drug-induced cell death. Therefore, counteracting the negative effects of hyperglycemia may positively improve the cancer cell death induced by chemotherapies. Recent studies showed that zinc supplementation may have beneficial effects on glycemic control. Here we aimed at evaluating whether ZnCl2 could counteract the high-glucose (HG) effects and consequently restore the drug-induced cancer cell death. At the molecular level we found that the HG-induced expression of genes known to be involved in chemoresistance (such as HIF-1α, GLUT1, and HK2 glycolytic genes, as well as NF-ΚB activity) was reduced by ZnCl2 treatment. In agreement, the adryamicin (ADR)-induced apoptotic cancer cell death was significantly impaired by HG and efficiently re-established by ZnCl2 cotreatment. Mechanistically, the ADR-induced c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) phosphorylation, inhibited by HG, was efficiently restored by ZnCl2. The JNK involvement in apoptotic cell death was assessed by the use of JNK dominant-negative expression vector that indeed impaired the ZnCl2 ability to restore drug-induced cell death in HG condition. Altogether, these findings indicate that ZnCl2 supplementation efficiently restored the drug-induced cancer cell death, inhibited by HG, by both sustaining JNK activation and counteracting the glycolytic pathway. © The Author(s) 2016
Women’s march on London: The importance of sister marches
No full textAli Cirone, LSE Fellow in Political Economy in the Department of Government, reflects on the Women’s March on London which took place on the 21 January 2017
EBV and KSHV Infection Dysregulates Autophagy to Optimize Viral Replication, Prevent Immune Recognition and Promote Tumorigenesis
No full textAutophagy is a catabolic process strongly involved in the immune response, and its dysregulation contributes to the onset of several diseases including cancer. The human oncogenic gammaherpesviruses, Epstein—Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), manipulate autophagy, either during the de novo infection or during the lytic reactivation, in naturally latently-infected lymphoma cells. In particular, the gammaherpesvirus infection reduces autophagy in immune cells, such as monocytes, resulting in the impairment of cell survival and cell differentiation into dendritic cells (DCs), which are essential for initiating and regulating the immune response. In the case of EBV, the reduction of autophagy in these cells, leading to p62 accumulation, activated the p62-NRF2-antioxidant response, reducing ROS, and further inhibiting autophagy. KSHV inhibits autophagy in monocytes by de-phosphorylating JNK2, altering the calpains⁻calpastatin balance and increasing the calpain activity responsible for the cleavage of ATG5. To further impair the immune response, KSHV also inhibits autophagy in differentiated DCs by hyper-phosphorylating STAT3. Conversely, when the lytic cycle is induced in vitro in latently-infected lymphoma B cells, both EBV and KSHV promote autophagy to enhance their replication, although the final autophagic steps are blocked through the down-regulation of Rab7. This strategy allows viruses to avoid the destructive environment of lysosomes, and to exploit the autophagic machinery for intracellular transportation. EBV and KSHV encode for proteins that may either inhibit or promote autophagy and, in addition, they can modulate the cellular pathways that control this process. In this review we will discuss the findings that indicate that autophagy is dysregulated by gammaherpesvirus to promote immune suppression, facilitate viral replication and contribute to the onset and maintenance of gammaherpesvirus-associated malignancies
ER Stress, UPR Activation and the Inflammatory Response to Viral Infection
No full textThe response to invading pathogens such as viruses is orchestrated by pattern recognition receptor (PRR) and unfolded protein response (UPR) signaling, which intersects and converges in the activation of proinflammatory pathways and the release of cytokines and chemokines that harness the immune system in the attempt to clear microbial infection. Despite this protective intent, the inflammatory response, particularly during viral infection, may be too intense or last for too long, whereby it becomes the cause of organ or systemic diseases itself. This suggests that a better understanding of the mechanisms that regulate this complex process is needed in order to achieve better control of the side effects that inflammation may cause while potentiating its protective role. The use of specific inhibitors of the UPR sensors or PRRs or the downstream pathways activated by their signaling could offer the opportunity to reach this goal and improve the outcome of inflammation-based diseases associated with viral infections
Research Productivity Among Canadian First Year Dermatology Residents: A 15 Year Analysis
No full textA retrospective review was conducted to obtain names of the residents that began training in Canadian dermatology residency programs between 2008 and 2022. Metrics reflective of research productivity (publication count, dermatology publications, authorship position, and H-index) were obtained from Scopus and trends were identified and evaluated using descriptive, univariate, and bivariate statistics. From the 10 Canadian residency programs, 371 dermatology residents producing 828 publications, of which 329 were dermatology-related were identified. Overall, 56% of residents had a minimum of one publication at the time of the match, with a mean of 2.23 + 4.27 publications and H-index of 1.36 + 2.23. A significant increase in all research productivity metrics was observed during the 2018 – 2022 period. Over the past 15 years, the amount of publications authored by incoming dermatology residents has increased significantly which may suggest an increased emphasis placed on medical research by medical students and residency programs
Cancer cells dysregulate PI3K/AKT/mTOR pathway activation to ensure their survival and proliferation: mimicking them is a smart strategy of gammaherpesviruses
No full textThe serine/threonine kinase mammalian target of rapamycin (mTOR) is the catalytic subunit of two complexes, mTORC1 and mTORC2, which have common and distinct subunits that mediate separate and overlapping functions. mTORC1 is activated by plenty of nutrients, and the two complexes can be activated by PI3K signaling. mTORC2 acts as an upstream regulator of AKT, and mTORC1 acts as a downstream effector. mTOR signaling integrates both intracellular and extracellular signals, acting as a key regulator of cellular metabolism, growth, and survival. A dysregulated activation of mTOR, as result of PI3K pathway or mTOR regulatory protein mutations or even due to the presence of cellular or viral oncogenes, is a common finding in cancer and represents a central mechanism in cancerogenesis. In the final part of this review, we will focus on the PI3K/AKT/mTOR activation by the human gammaherpesviruses EBV and KSHV that hijack this pathway to promote their-mediated oncogenic transformation and pathologies
Perturbation of bulk and selective macroautophagy, abnormal UPR activation and their interplay pave the way to immune dysfunction, cancerogenesis and neurodegeneration in ageing
No full textA plethora of studies has indicated that ageing is characterized by an altered proteostasis, ROS accumulation and a status of mild/chronic inflammation, in which macroautophagy reduction and abnormal UPR activation play a pivotal role. The dysregulation of these inter-connected processes favors immune dysfunction and predisposes to a variety of several apparently unrelated pathological conditions including cancer and neurodegeneration. Given the progressive ageing of the population, a better understanding of the mechanisms regulating autophagy, UPR and their interplay is needed in order to design new therapeutic strategies able to counteract the effects of ageing and concomitantly restrain the onset/progression of age-related diseases that represent a private and public health problem
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