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71.
Davide Busato Monica Mossenta Michele Dal Bo Paolo Macor Giuseppe Toffoli 《International journal of molecular sciences》2022,23(18)
Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers, with a 5-year survival rate of 7% and 80% of patients diagnosed with advanced or metastatic malignancies. Despite recent advances in diagnostic testing, surgical techniques, and systemic therapies, there remain limited options for the effective treatment of PDAC. There is an urgent need to develop targeted therapies that are able to differentiate between cancerous and non-cancerous cells to reduce side effects and better inhibit tumor growth. Antibody-targeted strategies are a potentially effective option for introducing innovative therapies. Antibody-based immunotherapies and antibody-conjugated nanoparticle-based targeted therapies with antibodies targeting specific tumor-associated antigens (TAA) can be proposed. In this context, glypican-1 (GPC1), which is highly expressed in PDAC and not expressed or expressed at very low levels in non-malignant lesions and healthy pancreatic tissues, is a useful TAA that can be achieved by a specific antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy. In this review, we describe the main clinical features of PDAC. We propose the proteoglycan GPC1 as a useful TAA for PDAC-targeted therapies. We also provide a digression on the main developed approaches of antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy, which can be used to target GPC1. 相似文献
72.
Maria Antonietta Grignano Stefania Bruno Simona Viglio Maria Antonietta Avanzini Marta Tapparo Marina Ramus Stefania Croce Chiara Valsecchi Eleonora Francesca Pattonieri Gabriele Ceccarelli Federica Manzoni Annalia Asti Carmelo Libetta Vincenzo Sepe Paolo Iadarola Marilena Gregorini Teresa Rampino 《International journal of molecular sciences》2022,23(18)
We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system. 相似文献
73.
Franco Bisceglie Giorgio Pelosi Nicol Orsoni Marianna Pioli Mauro Carcelli Paolo Pelagatti Silvana Pinelli Peter J. Sadler 《International journal of molecular sciences》2022,23(14)
We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N′)L][PF6]2 containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT). 相似文献
74.
Agnese Filippello Stefania Di Mauro Alessandra Scamporrino Sebastiano Alfio Torrisi Gian Marco Leggio Antonino Di Pino Roberto Scicali Maurizio Di Marco Roberta Malaguarnera Francesco Purrello Salvatore Piro 《International journal of molecular sciences》2022,23(14)
Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy. 相似文献
75.
Valentina Doldi Mara Lecchi Silva Ljevar Maurizio Colecchia Elisa Campi Giovanni Centonze Cristina Marenghi Tiziana Rancati Rosalba Miceli Paolo Verderio Riccardo Valdagni Paolo Gandellini Nadia Zaffaroni 《International journal of molecular sciences》2022,23(14)
Prostate cancer (PCa) ranges from indolent to aggressive tumors that may rapidly progress and metastasize. The switch to aggressive PCa is fostered by reactive stroma infiltrating tumor foci. Therefore, reactive stroma-based biomarkers may potentially improve the early detection of aggressive PCa, ameliorating disease classification. Gene expression profiles of PCa reactive fibroblasts highlighted the up-regulation of genes related to stroma deposition, including periostin and sparc. Here, the potential of periostin as a stromal biomarker has been investigated on PCa prostatectomies by immunohistochemistry. Moreover, circulating levels of periostin and sparc have been assessed in a low-risk PCa patient cohort enrolled in active surveillance (AS) by ELISA. We found that periostin is mainly expressed in the peritumoral stroma of prostatectomies, and its stromal expression correlates with PCa grade and aggressive disease features, such as the cribriform growth. Moreover, stromal periostin staining is associated with a shorter biochemical recurrence-free survival of PCa patients. Interestingly, the integration of periostin and sparc circulating levels into a model based on standard clinico-pathological variables improves its performance in predicting disease reclassification of AS patients. In this study, we provide the first evidence that circulating molecular biomarkers of PCa stroma may refine risk assessment and predict the reclassification of AS patients. 相似文献
76.
Antonio Camurri Paolo Franchi Francesca Gandolfo Renato Zaccaria 《Journal of Intelligent and Robotic Systems》1993,8(1):99-123
In this paper, we propose a class of algorithms for the sub-optimal solution of a particular class of problems of process scheduling, particularly focusing on a case study in the area of flexible manufacturing systems (FMSs). The general class of problems we face in our approach is characterized as follows: there is a set of concurrent processes, each formed by a number of temporally related tasks (segments). Tasks are executable by alternate resource sets, different both in performance and costs. Processes and tasks are characterized by release times, due dates, and deadlines. Time constraints are also present in the availability of each resource in resource sets. It has been proven that such a problem does not admit an algorithm for an optimal solution in polynomial time. Our proposed algorithm finds a sub-optimal schedule according to a set of optimization criteria, based on task and process times (earliness, tardiness), and/or time independent costs of resources. Our approach to process scheduling is based on Timed Coloured Petri Nets. We describe the structure of the coordination and scheduling algorithms, concentrating on (i) the general-purpose component, and (ii) the application-dependent component. In particular, the paper focuses on the following issues: (i) theautomatic synthesis of Petri net models of the coordination subsystem, starting from the problem knowledge base; (ii) the dynamic behavior of the coordination subsystem, whose kernel is a High Level Petri net executor, a coordination process based on an original, general purpose algorithm; (iii) the structure of the real-time scheduling subsystem, based on particular heuristic sub-optimal multi-criteria algorithms. Furthermore, the paper defines the interaction mechanisms between the coordination and scheduling subsystems. Our approach clearly distinguishes the mechanism of the net execution from the decision support system. Two conceptually distinct levels, which correspond to two different, interacting implementation modules in the prototype CASE tool, have been defined: theexecutor and thescheduler levels. One of the outstanding differences between these levels is that the executor is conceived as a fast, efficient coordination process, without special-purpose problem-solving capabilities in case of conflicts. The scheduler, on the other hand, is the adaptive, distributed component, whose behavior may heavily depend on the problem class. If the scheduler fails, the executor is, in any case, able to proceed with a general-purpose conflict resolution strategy. Experimental results on the real-time performance of the kernel of the implemented system are finally shown in the paper. The approach described in this paper is at the basis of a joint project with industrial partners for the development of a CASE tool for the simulation of blast furnaces. 相似文献
77.
Claudio Rocchini Paolo Cignoni Fabio Ganovelli Claudio Montani Paolo Pingi Roberto Scopigno 《The Visual computer》2004,20(2-3):149-164
A new algorithm for the integration of partially overlapping range images into a triangular mesh is presented. The algorithm consists of three main steps: it locates the intersections between the range surfaces and a reference grid chosen by the user, then merges all nearly coincident and redundant intersections according to a proximity criterion, and, finally, reconstructs the merged surface(s) from the filtered intersection set.
Compared with previous methods, which adopt a volumetric approach, our algorithm shows lower computational costs and improves the accuracy of the surfaces produced. It takes into account the quality of the input measurements and is able to patch small holes corresponding to the parts of the 3D scanned object that were not observed by the acquisition device.
The algorithm has been tested on several datasets of range maps; graphical and numeric results are reported. 相似文献
78.
Paolo Ria Antonio De Pascalis Anna Zito Silvia Barbarini Marcello Napoli Antonietta Gigante Gian Pio Sorice 《International journal of molecular sciences》2023,24(1)
Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy. 相似文献
79.
Francesco Borgia Paolo Custurone Federica Li Pomi Mario Vaccaro Clara Alessandrello Sebastiano Gangemi 《International journal of molecular sciences》2023,24(1)
Interleukin (IL)-37 and IL-33 are among the latest cytokines identified, playing a role in several inflammatory conditions, spanning from systemic conditions to tumors to localized diseases. As newly discovered interleukins, their role is still scarcely understood, but their potential role as therapeutic targets or disease activity markers suggests the need to reorganize the current data for a better interpretation. The aim of this review is to collect and organize data produced by several studies to create a complete picture. The research was conducted on the PubMed database, and the resulting articles were sorted by title, abstract, English language, and content. Several studies have been assessed, mostly related to atopic dermatitis and immunologic pathways. Collective data demonstrates a pro-inflammatory role of IL-33 and an anti-inflammatory one for IL-37, possibly related to each other in an IL-33/IL-37 axis. Although further studies are needed to assess the safety and plausibility of targeting these two interleukins for patients affected by skin conditions, the early results indicate that both IL-33 and IL-37 represent markers of disease activity. 相似文献
80.
Aniello Maiese Alice Chiara Manetti Naomi Iacoponi Eleonora Mezzetti Emanuela Turillazzi Marco Di Paolo Raffaele La Russa Paola Frati Vittorio Fineschi 《International journal of molecular sciences》2022,23(13)
The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were “wound”, “lesion”, “vitality”, “evaluation”, “immunohistochemistry”, “proteins”, “electrolytes”, “mRNAs”, and “miRNAs” in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation. 相似文献