Sulfoglycolipids analogues as new molecules for tumor treatment

The sulfoglycolipids sulfoquinovosylacylglycerols(SQAG) are abundant sulfur-containing glycerolipids that are associated with photosynthetic organisms especially with a large number of marine algae. Their main structural feature is the anionic head group constituent sulfoquinovose, a derivative of glucose in which the 6-hydroxyl is replaced by a sulfonate group, \uf061-linked to the sn-3 position of a diacylglycerol1. Recently reported biological activities of SQAGs, including inhibitory effects on HIV-reverse transcriptase, and mammalian DNA polymerase, proliferation of some cancer cell lines, angiogenesis (especially when coupled with tumor radiotherapy), and apoptosis induction, make these compounds very attractive for their potential in cancer therapy. Also, extractive SQAG mixtures are known to inhibit in vitro TPA induced tumor promotion stage. To obtain new active compounds for cancer therapy by structural modification of natural SQAGs, SQAG analogues have been synthesized in which the sulfoquinovose moiety is linked to the 2 position of glycerol carrying acyl chains of different length. Similar compounds in fact, with a 6\u2019-hydroxyl instead of a 6\u2019-sulfonate (namely some glycoglycerolipid analogues), are known to be active as anti-tumor-promoters in TPA promoted carcinogenesis in vitro and in vivo experiments. A synthetic strategy has been used to selectively insert the proper chemical functionalities (i.e. sulfonate and acyl chains) at the desired positions of the previously prepared glucosylglycerol skeleton to obtain the target compounds. Biological evaluation of anti-tumor activities will be performed including the study of their chemopreventing potential

Chemoenzymatic synthesis of sulfoquinovosylmonoacylglycerols (SQMG) as anti-tumor-promoters

During our search for new glycoglycerolipids active in cancer chemoprevention, in recent years we have synthesized a number of esters of 2-O-beta-D-glycosylglycerols in which the length, shape, number and position of the acyl chain, and the type of sugar (alpha\uf020and beta glucose or galactose) were varied. These compounds were found to be very active in inhibiting the tumor-promoting activity of the phorbol ester TPA both in in vitro and in in vivo tests, being such activities mainly influenced by the changes of the acyl chains length. Sulfoquinovosylacylglycerols are acylated sulfoglycolipids in which sulfoquinovose (6-deoxy-6-sulfo-glucose) is alpha-linked to the sn-3 position of glycerol. These compounds exhibit noteworthy biological activities, that make them very attractive for their use in cancer therapy. Here we report the synthesis of 6\u2019-sulfo-derivatives (SQMG) based on the skeleton of 2-O-beta-D-glucosylglycerol to which previously synthesized biologically active glucoglycerolipid analogues are related. A chemoenzymatic strategy has been used to selectively insert the proper chemical functionalities (i.e. acyl chain) at the desired position of glucosylglycerol to obtain the target compounds. Their potential as anti-tumor-promoters will be also discussed

Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region

Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, >200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 201

Editorial: Congenital and perinatal infections: How to prevent sequelaes in neonates and children

The current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmingly absorbed attention and health resources for 2 years, allowing us to reflect that infections are a permanent health and social problem, causing morbidity and mortality. They require organization, important prevention measures, and containment. This is particularly true in the neonatal age, where infections remain a complex problem with serious consequences

LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases

DTM generation through UAV survey with a Fisheye camera on a vineyard

Precision agriculture recommends a sustainable employment of nutrients and water, according to the site-specific crop requirements. In this context, the knowledge of soil characteristics allows to appropriately manage resources. Even the topography can influence the spatial distribution of the water on a field. This work focuses on the production of high-resolution Digital Terrain Model (DTM) in agriculture by photogrammetric processing fisheye images, acquired with very light Unmanned Aerial Vehicle (UAV). Particular attention is given to the data processing procedures and to the assessment of the quality of the results, considering the peculiarity of the acquired images. An experimental test has been carried out on a vineyard located in Monzambano, Northern Italy, through photogrammetric survey with Parrot Bebop 2 UAV. It has been realized at the end of the vegetation season, to investigate the ground without any impediment due to the presence of leaves or branches. In addition, the survey has been used for evaluating the performance of Bebop fisheye camera in viticulture. Different flight strategies have been tested, together with different Ground Control Points (GCPs) and Check Points (CPs) configurations and software packages. The computed DTMs have been compared with a reference model obtained through Kriging interpolation of GNSS-RTK measurements. Residuals on CPs are of the order of 0.06 m, for all the considered scenarios, that for agricultural applications is by far sufficient. The photogrammetric DTMs show a good agreement with the reference one

Long non-coding RNAs in B-cell malignancies: a comprehensive overview

B-cell malignancies constitute a large part of hematological neoplasias. They represent a heterogeneous group of diseases, including Hodgkin's lymphoma, most non-Hodgkin's lymphomas (NHL), some leukemias and myelomas. B-cell malignancies re\uef\uac\u82ect de\uef\uac\u81ned stages of normal B-cell differentiation and this represents the major basis for their classification. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides, for which many recent studies have demonstrated a function in regulating gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including hematological malignancies. The involvement of lncRNAs in cancer initiation and progression and their attractive features both as biomarker and for therapeutic research are becoming increasingly evident. In this review, we summarize the recent literature to highlight the status of the knowledge of lncRNAs role in normal B-cell development and in the pathogenesis of B-cell tumors

Mechanisms of immune evasion in multiple myeloma: Open questions and therapeutic opportunities

Multiple myeloma (MM) is the second most common hematologic malignancy, charac-terized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immuno-suppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients

Replacement of miR-155 elicits tumor suppressive activity and antagonizes bortezomib resistance in multiple myeloma

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given the lower miR-155 levels in bortezomib-resistant as compared to sensitive MM cells, we analyzed the possible involvement of miR-155 in bortezomib resistance. Importantly, miR-155 replacement enhanced bortezomib anti-tumor activity both in vitro and in vivo in a xenograft model of human MM. In primary MM cells, we observed an inverse correlation between miR-155 and the mRNA encoding the proteasome subunit gene PSMβ5, whose dysregulation has been largely implicated in bortezomib resistance, and we validated PSMβ5 30UTR mRNA targeting, along with reduced proteasome activity, by miR-155. Collectively, our findings demonstrate that miR-155 elicits anti-MM activity, likely via proteasome inhibition, providing the framework for miR-155-based anti-MM therapeutic strategies