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Alternative therapeutic strategies in diabetes management

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World Journal of Diabetes 2024年第6期15卷 1142-1161页

作者： alessia Annicchiarico Barbara Barile Cinzia Buccoliero Grazia Paola Nicchia Giacomina Brunetti Department of Biosciences Biotechnologies and EnvironmentUniversity of Bari Aldo MoroBari 70125Italy

Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreaticβcells,insulin resistance in peripheral tissues,or both,and results in a non-sufficient production of insulin.To adjust blood glucose levels,diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity.With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities,different strategies have been investigated.The first approaches included enhancing endogenousβcell activity or transplanting new islets.The protocol for this kind of intervention has recently been optimized,leading to standardized procedures.It is indicated for diabetic patients with severe hypoglycemia,complicated by impaired hypoglycemia awareness or exacerbated glycemic lability.Transplantation has been associated with improvement in all comorbidities associated with diabetes,quality of life,and survival.However,different trials are ongoing to further improve the beneficial effects of transplantation.Furthermore,to overcome some limitations associated with the availability of islets/pancreas,alternative therapeutic strategies are under evaluation,such as the use of mesenchymal stem cells(MSCs)or induced pluripotent stem cells for transplantation.The cotransplantation of MSCs with islets has been successful,thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms,including exosome release.The use of induced pluripotent stem cells is recent and requires further investigation.The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities,such as wound healing.Despite the number of advantages of the direct injection of MSCs,new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results.In conclusion,this paper offered an overview

关键词： Diabetes Pancreas/islet transplantation Mesenchymal stem cells Induced pluripotent stem cells Exosomes Scaffolds

Enhancing sensitivity of triple-negative breast cancer to DNA-damaging therapy through chemical inhibition of the m6A methyltransferase METTL3

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Cancer Communications 2024年第2期44卷 282-286页

作者： Bianca Cesaro alessia Iaiza Fabio Piscopo Marco Tarullo Eleonora Cesari Dante Rotili Antonello Mai Alberto Diana Michela Londero Luca Del Giacco Riccardo Masetti Alba Di Leone Chiara Naro Silvia Masciarelli Giulia Fontemaggi Claudio Sette Francesco Fazi Alessandro Fatica Department of Anatomical HistologicalForensic&Orthopedic SciencesSection of Histology&Medical EmbryologySapienza University of RomeRomeItaly Department of Biology and Biotechnologies“Charles Darwin” Sapienza University of RomeRomeItaly GSTeP Organoids Research Core Facility Fondazione Policlinico A.Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)RomeItaly Department of Drug Chemistry and Technologies Sapienza University of RomeRomeItaly Pasteur Institute Cenci-Bolognetti FoundationSapienza University of RomeRomeItaly Department of BioSciences University of MilanMilanItaly Multidisciplinary Breast Center Dipartimento Scienze della Salute della Donna e del Bambino e di SanitàPubblicaCatholic University of the Sacred HeartRomeItaly Department of Neuroscience Section of Human AnatomyCatholic University of the Sacred HeartRomeItaly Oncogenomic and Epigenetic Unit IRCCS Regina Elena National Cancer InstituteRomeItaly

Dear Editor,N 6-methyladenosine(m^(6)A)is a critical mRNA modi-fication catalyzed by the enzyme methyltransferase-like 3(METTL3),with implications in RNA metabolism.METTL3 upregulation is associated with cancer progre... 详细信息

关键词： cancer methyltransferase metastasis

A microbial-derived succinylated bile acid to safeguard liver health

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四川生理科学杂志 2024年第5期46卷 1134-1134页

作者： alessia Perino 不详

In this issue of Cell,Nie and co-authors report that the microbe-derived bile acid(BA)3-succinylated cholic acid protects against the progression of metabolic dysfunction-associated liver disease.Intriguingly,its protective mechanism does not involve traditional BA signaling pathways but is instead linked to the proliferation of the commensal microbe Akkermansia muciniphila.

关键词： bile protective liver

Non-toxic, high selectivity process for the extraction of precious metals from waste printed circuit boards

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Frontiers of Environmental Science & Engineering 2023年第10期17卷 65-74页

作者： Giulia Merli Alessandro Becci alessia Amato Francesca Beolchini Department of Life and Environmental Sciences Polytechnic University of MarcheAncona 60131Italy

The work presented here focused on the extraction of gold (Au), silver (Ag) and palladium (Pd) from electronic waste using a solution of ammonium thiosulfate. Thiosulfate was used as a valid alternative to cyanide for precious metal extractions, due to its non-toxicity and high selectivity. The interactions between sodium thiosulfate, total ammonia/ammonium, precious metal concentrations and the particle size of the waste printed circuit boards (WPCBs) were studied by the response surface methodology (RSM) and the principal component analysis (PCA) to maximize precious metal mobilization. Au extraction reached a high efficiency with a granulometry of less than 0.25 mm, but the consumption of reagents was high. On the other hand, Ag extraction depended neither on thiosulfate/ammonia concentration nor granulometry of WPCBs and it showed efficiency of 90% also with the biggest particle size (0.50 < Ø < 1.00 mm). Pd extraction, similarly to Au, showed the best efficiency with the smallest and the medium WPCB sizes, but required less reagents compared to Au. The results showed that precious metal leaching is a complex process (mainly for Au, which requires more severe conditions in order to achieve high extraction efficiencies) correlated with reagent concentrations, precious metal concentrations and WPCB particle sizes. These results have great potentiality, suggesting the possibility of a more selective recovery of precious metals based on the different granulometry of the WPCBs. Furthermore, the high extraction efficiencies obtained for all the metals bode well in the perspective of large-scale applications.

关键词： Thiosulfate Printed circuit boards Precious metals Leaching Hydrometallurgy

Empowering digital twins with eXtended reality collaborations

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Virtual Reality & Intelligent Hardware 2022年第6期4卷 487-505页

作者： Lorenzo STACCHIO alessia ANGELI Gustavo MARFIA Department for Life Quality Studies University of BolognaItaly Department of Computer Science and Engineering University of BolognaItaly Department of the Arts University of BolognaItaly

Background The advancements of Artificial Intelligence,Big Data Analytics,and the Internet of Things paved the path to the emergence and use of Digital Twins(DTs)as technologies to“twin”the life of a physical entity in different fields,ranging from industry to healthcare.At the same time,the advent of eXtended Reality(XR)in industrial and consumer electronics has provided novel paradigms that may be put to good use to visualize and interact with DTs.XR technologies can support human-to-human interactions for training and remote assistance and could transform DTs into collaborative intelligence tools.Methods We here present the Human Collaborative Intelligence empowered Digital Twin framework(HCLINT-DT)integrating human annotations(e.g.,textual and vocal)to allow the creation of an all-in-one-place resource to preserve such knowledge.This framework could be adopted in many fields,supporting users to learn how to carry out an unknown process or explore others’past experiences.Results The assessment of such a framework has involved implementing a DT supporting human annotations,reflected in both the physical world(Augmented Reality)and the virtual one(Virtual Reality).Con-clusions The outcomes of the interface design assessment confirm the interest in developing HCLINT-DT-based applications.Finally,we evaluated how the proposed framework could be translated into a manufacturing context.

关键词： Digital twin eXtended reality Human collaborative intelligence

Catania flatfoot score:A diagnostic-therapeutic evaluation tool in children

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World Journal of Orthopedics 2023年第10期14卷 755-762页

作者： Andrea Vescio Gianluca Testa alessia Caldaci Marco Sapienza Vito Pavone Department of General Surgery and Medical Surgical Specialties Section of Orthopaedics and TraumatologyA.O.U.Policlinico“Rodolico-San Marco”University of CataniaCatania 95123Italy

BACKGROUND Flexible flatfoot(FFF)is a very common condition in children,but no evidencebased guidelines or assessment tools exist.Yet,surgical indication is left to the surgeon’s experience and preferences.AIM To develop a functional clinical score for FFF[Catania flatfoot(CTF)score]and a measure of internal consistency;to evaluate inter-observer and intra-observer reliability of the CTF Score;to provide a strong tool for proper FFF surgical indication.METHODS CTF is a medically compiled score of four main domains for a total of twelve items:Patient features,Pain,Clinical Parameters,and Functionality.Each item refers to a specific rate.Five experienced observers answered 10 case reports according to the CTF.To assess inter-and intra-observer reliability of the CTF score,the intra-class correlation coefficients’(ICCs)statistics test was performed,as well as to gauge the correlation between the CTF score and the surgical or conservative treatment indication.Values of 75%were chosen as the score cut-off for surgical indication.Sensitivity,specificity,positive likelihood ratio(PLHR),negative likelihood ratio(NLHR),positive predictive value(PPV),and negative predictive value(NPV).RESULTS Overall interobserver reliability ICC was 0.87[95%confidence interval(CI):0.846-0.892;P<0.001].Overall intra-observer reliability ICC was 0.883(95%CI:0.854-0.909;P<0.001).A direct correlation between the CTF score and surgical treatment indication[Pearson correlation coefficient=0.94(P<0.001)]was found.According to the 75%cut-off,the sensitivity was 100%(95%CI:83.43%-100%),specificity was 85.71%(95%CI:75.29%-92.93%),PLHR was 7(95%CI:3.94-12.43),NLHR was 0(95%CI:0-0),PPV was 75%(95%CI:62.83%-84.19%)and NPV was 100%(95%CI:100%-100%).CONCLUSION CTF represents a useful tool for orthopedic surgeons in the FFF evaluation.The CTF score is a quality questionnaire to reproduce suitable clinical research,survey studies,and clinical practice.Moreover,the 75%cutoff is an important threshold for surgical indication and helps in the decision-making

关键词： Pes planus Score Assessment Clinic Surgery Outcome Reparability

Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT):An open-source behavioral apparatus for intertemporal choice testing in rodents

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Animal Models and Experimental Medicine 2023年第6期6卷 619-626页

作者： Andrea Stefano Moro Daniele Saccenti alessia Seccia Mattia Ferro Antonio Malgaroli Jacopo Lamanna Department of Psychology Sigmund Freud UniversityMilanItaly Center for Behavioral Neuroscience and Communication(BNC) Vita-Salute San Raffaele UniversityMilanItaly Transcranial Magnetic Stimulation Unit Italian Psychotherapy ClinicsMilanItaly Faculty of Psychology Vita-Salute San Raffaele UniversityMilanItaly San Raffaele Turro IRCCS Ospedale San RaffaeleMilanItaly

Advancements in neuroscience research present opportunities and challenges,requiring substantial resources and funding.To address this,we describe here“Poke And Delayed Drink Intertemporal Choice Task(POKE-ADDICT)”,an open-source,versatile,and cost-effective apparatus for intertemporal choice testing in rodents.This allows quantification of delay discounting(DD),a cross-species phenomenon observed in decision making which provides valuable insights into higher-order cognitive functioning.In DD,the subjective value of a delayed reward is reduced as a function of the delay for its receipt.Using our apparatus,we implemented an effective intertemporal choice paradigm for the quantification of DD based on an adjusting delayed amount(ADA)algorithm using mango juice as a reward.Our paradigm requires limited training,a few 3D-printed parts and inexpensive electrical components,including a Raspberry Pi control unit.Furthermore,it is compatible with several in vivo procedures and the use of nose pokes instead of levers allows for faster task learning.Besides the main application described here,the apparatus can be further extended to implement other behavioral tests and protocols,including standard operant conditioning.In conclusion,we describe a versatile and cost-effective design based on Raspberry Pi that can support research in animal behavior,decision making and,more specifically,delay discounting.

关键词： decision making delay discounting intertemporal choice open source

AdipoRon and Pancreatic Ductal Adenocarcinoma:a future perspective in overcoming chemotherapyinduced resistance?

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Cancer Drug Resistance 2022年第3期5卷 625-636页

作者： Luigi Sapio Angela Ragone Annamaria Spina alessia Salzillo Silvio Naviglio Department of Precision Medicine University of Campania“Luigi Vanvitelli”Naples 80138Italy

The latest scientific knowledge has provided additional insights accountable for the worst prognosis for pancreatic ductal adenocarcinoma(PDAC).Among the causative factors,the aptitude to develop resistance towards approved medications denotes the master key for understanding the lack of improvement in PDAC survival over the years.Even though several compounds have achieved encouraging results at preclinical stage,no new adjuvant agents have reached the bedside of PDAC patients lately.The adiponectin receptor agonist AdipoRon is emerging as a promising anticancer drug in different cancer models,particularly in PDAC.Building on the existing findings,we recently reinforced its candidacy in PDAC cells,proposing AdipoRon either as a suitable partner in gemcitabinebased treatment or as an effective drug in resistant cells.Crossing the current state-of-the-art,herein we provide a critical perspective on AdipoRon to figure out whether this receptor agonist can potentially be considered a future therapeutic choice in overcoming chemotherapy-induced resistance,expressly in PDAC.

关键词： PDAC AdipoRon gemcitabine resistance

Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells:Potential implications for their clinical use

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World Journal of Stem Cells 2023年第5期15卷 400-420页

作者： Vitale Miceli Giovanni Zito Matteo Bulati alessia Gallo Rosalia Busà Gioacchin Iannolo Pier Giulio Conaldi Department of Research IRCCS ISMETT(Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione)Palermo 90127Italy

Mesenchymal stromal/stem cells(MSCs)have shown significant therapeutic potential,and have therefore been extensively investigated in preclinical studies of regenerative medicine.However,while MSCs have been shown to be safe as a cellular treatment,they have usually been therapeutically ineffective in human diseases.In fact,in many clinical trials it has been shown that MSCs have moderate or poor efficacy.This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs.Recently,specific priming strategies have been used to improve the therapeutic properties of MSCs.In this review,we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs.We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes.Particularly,while hypoxic priming can be used primarily for the treatment of acute diseases,inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders.The shift in approach from regeneration to inflammation implies,in MSCs,a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways.The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

关键词： Mesenchymal stromal/stem cells Mesenchymal stromal/stem cell therapeutic properties Mesenchymal stromal/stem cell paracrine effects Mesenchymal stromal/stem cell priming Pro-inflammatory priming Hypoxic priming,3D culture priming