Phosphoinositide 3-kinases in platelets, thrombosis and therapeutics

2020 ◽  
Vol 477 (22) ◽  
pp. 4327-4342
Author(s):  
Agnès Ribes ◽  
Antoine Oprescu ◽  
Julien Viaud ◽  
Karim Hnia ◽  
Gaëtan Chicanne ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Second Messenger ◽  
Expression Regulation ◽  
Class I ◽  
Biological Processes ◽  
Class Iii ◽  
Platelet Signaling ◽  
New Perspective ◽  
Made In

Our knowledge on the expression, regulation and roles of the different phosphoinositide 3-kinases (PI3Ks) in platelet signaling and functions has greatly expanded these last twenty years. Much progress has been made in understanding the roles and regulations of class I PI3Ks which produce the lipid second messenger phosphatidylinositol 3,4,5 trisphosphate (PtdIns(3,4,5)P3). Selective pharmacological inhibitors and genetic approaches have allowed researchers to generate an impressive amount of data on the role of class I PI3Kα, β, δ and γ in platelet activation and in thrombosis. Furthermore, platelets do also express two class II PI3Ks (PI3KC2α and PI3KC2β), thought to generate PtdIns(3,4)P2 and PtdIns3P, and the sole class III PI3K (Vps34), known to synthesize PtdIns3P. Recent studies have started to reveal the importance of PI3KC2α and Vps34 in megakaryocytes and platelets, opening new perspective in our comprehension of platelet biology and thrombosis. In this review, we will summarize previous and recent advances on platelet PI3Ks isoforms. The implication of these kinases and their lipid products in fundamental platelet biological processes and thrombosis will be discussed. Finally, the relevance of developing potential antithrombotic strategies by targeting PI3Ks will be examined.

scholarly journals Reacting to the Emergency by Opening Perspectives. Design-driven knit therapy as a adaptable tool to answer the change

2020 ◽  
Vol 13 (3) ◽  
pp. 646-657
Author(s):  
Martina Motta ◽  
Giovanni Maria Conti ◽  
Martina Micheli
Keyword(s):  
Social Media ◽  
Hospital Environment ◽  
Therapeutic Effects ◽  
Small Communities ◽  
Service Creation ◽  
Physical Level ◽  
New Perspective ◽  
Ongoing Project ◽  
Made In

When the COVID-19 emergency raised, the entire world -and small communities with it- had to stop, adapt, find ways to face the big ongoing challenge. The article reports the reaction and the changes undertaken with an ongoing project that was, in February 2020, experimenting, inside the hospital environment, the therapeutic effects of knitting on people with physical and psychological pathologies. The project, driven by scientific studies made in universities, hospitals and research centers worldwide, had the aim to bring the intervention of designers on the topic, to answer the emerged need to promote research in what is considered a low-investigated and high-promising field. Experimental pilot actions, designed and led by designers on-field, were going on when the emergency changed the scenario, limited the environment, shifted the eye on a new, wider target of healthy people, made knitting a tool to face new circumstances and improve everyday-life quality.Observing the newly emerged scenario and the spontaneous initiatives risen on the web (and on social media in particular) to help individuals in spending the forced time at home in meaningful ways, designers involved in the ongoing project identified in knitting an activity that could be beneficial on a psychological and physical level also for quarantined individuals. The project took a new perspective and evolved in the #IOLAVOROAMAGLIA (#IKNIT) social media campaign, linked to the globally spread #STAYHOME campaign, aimed at inviting people to remain home for preventing the diffusion of the infection, while proposing at the same time new solutions for positively living the emergency times. #IOLAVOROAMAGLIA was embraced by many users and it also became a weekly scheduled live virtual workshop, with a direct reference to the workshops in the hospital of XXXX, temporarily stopped during lockdown.The two projects, on-field and online, proved how knitting can be a meaningful solution not only for healthcare, but also for the daily life of people, both in normal times and in emergency situations.Moreover, the role of the designer and of a design driven approach proved to be fundamental, for the product and service creation, improvement and consolidation and for its communication for valorization and promotion.

scholarly journals Recent advances in understanding and managing dystonia

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1124 ◽  
Author(s):  
Stephen Tisch
Keyword(s):  
Focused Ultrasound ◽  
Brain Network ◽  
Imaging Genetics ◽  
Treatment Modalities ◽  
Biological Processes ◽  
New Treatment ◽  
Clinical Advances ◽  
Deep Brain ◽  
Made In

Within the field of movement disorders, the conceptual understanding of dystonia has continued to evolve. Clinical advances have included improvements in recognition of certain features of dystonia, such as tremor, and understanding of phenotypic spectrums in the genetic dystonias and dystonia terminology and classification. Progress has also been made in the understanding of underlying biological processes which characterize dystonia from discoveries using approaches such as neurophysiology, functional imaging, genetics, and animal models. Important advances include the role of the cerebellum in dystonia, the concept of dystonia as an aberrant brain network disorder, additional evidence supporting the concept of dystonia endophenotypes, and new insights into psychogenic dystonia. These discoveries have begun to shape treatment approaches as, in parallel, important new treatment modalities, including magnetic resonance imaging-guided focused ultrasound, have emerged and existing interventions such as deep brain stimulation have been further refined. In this review, these topics are explored and discussed.

scholarly journals Wnt signaling in lung development, regeneration, and disease progression

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cody J. Aros ◽  
Carla J. Pantoja ◽  
Brigitte N. Gomperts
Keyword(s):  
Wnt Signaling ◽  
Disease Progression ◽  
Lung Development ◽  
Wnt Signaling Pathway ◽  
Directed Differentiation ◽  
Biological Processes ◽  
Airway Conductance ◽  
Made In

AbstractThe respiratory tract is a vital, intricate system for several important biological processes including mucociliary clearance, airway conductance, and gas exchange. The Wnt signaling pathway plays several crucial and indispensable roles across lung biology in multiple contexts. This review highlights the progress made in characterizing the role of Wnt signaling across several disciplines in lung biology, including development, homeostasis, regeneration following injury, in vitro directed differentiation efforts, and disease progression. We further note uncharted directions in the field that may illuminate important biology. The discoveries made collectively advance our understanding of Wnt signaling in lung biology and have the potential to inform therapeutic advancements for lung diseases.

scholarly journals The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Paz Nombela ◽  
Borja Miguel-López ◽  
Sandra Blanco
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Therapeutic Potential ◽  
Biological Processes ◽  
Rna Modifications ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
Made In

AbstractRNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

The Role of Morning Plasma Cortisol in Obesity: A Bi-directional Mendelian Randomization Study

2022 ◽  
Author(s):  
Xiaohui QI ◽  
Bin CUI ◽  
Min CAO
Keyword(s):  
Genetic Variants ◽  
Plasma Cortisol ◽  
Mendelian Randomization ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Reverse Causality ◽  
Obese People ◽  
Obesity Class

Abstract Context Cortisol, an important hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is associated with obesity. However, it is unclear whether the relationship between cortisol and obesity is causal or could be explained by reverse causality. Objective This work aims to assess the role of morning plasma cortisol in clinical classes of obesity. Methods In this bi-directional two-sample Mendelian Randomization (MR) study, cortisol-associated genetic variants were obtained from the CORtisol NETwork consortium (n = 12,597). The primary outcomes were obesity class I (BMI ≥ 30 kg/m 2), class II (BMI ≥ 35 kg/m 2), and class III (BMI ≥ 40kg/m 2). Inverse variance weighting (IVW) method was used as the main analysis, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, genetic variants predicting clinical classes of obesity were applied to the cortisol GWAS. Results Genetically predicted cortisol was associated with reduced risk of obesity class I (OR = 0.905; 95% CI, 0.865-0.946; p < 0.001). Evidence from bi-directional MR showed that obesity class II and class III were associated with lower cortisol levels ((class II-cortisol OR = 0.953; 95% CI, 0.923-0.983; p = 0.002); (class III-cortisol OR = 0.955; 95% CI, 0.942-0.967; p < 0.001)), indicating reverse causality between cortisol and obesity. Conclusions This study demonstrates that cortisol is negatively associated with obesity and vice versa. Together, these findings suggest that blunted morning plasma cortisol secretion may be responsible for severe obesity. Regulating morning plasma secretion might be a prevention measure for obese people.

scholarly journals Distinct roles of class I and class III phosphatidylinositol 3-kinases in phagosome formation and maturation

2001 ◽  
Vol 155 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Otilia V. Vieira ◽  
Roberto J. Botelho ◽  
Lucia Rameh ◽  
Saskia M. Brachmann ◽  
Tsuyoshi Matsuo ◽  
...  
Keyword(s):  
Functional Role ◽  
Fluorescent Proteins ◽  
Class I ◽  
Class Iii ◽  
Phosphatidylinositol 3 Kinase ◽  
Intracellular Parasites ◽  
Selective Ablation ◽  
Phagosomal Membrane ◽  
Phosphatidylinositol 3

Phagosomes acquire their microbicidal properties by fusion with lysosomes. Products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for phagosome formation, but their role in maturation is unknown. Using chimeric fluorescent proteins encoding tandem FYVE domains, we found that phosphatidylinositol 3-phosphate (PI[3]P) accumulates greatly but transiently on the phagosomal membrane. Unlike the 3′-phosphoinositides generated by class I PI 3-kinases which are evident in the nascent phagosomal cup, PI(3)P is only detectable after the phagosome has sealed. The class III PI 3-kinase VPS34 was found to be responsible for PI(3)P synthesis and essential for phagolysosome formation. In contrast, selective ablation of class I PI 3-kinase revealed that optimal phagocytosis, but not maturation, requires this type of enzyme. These results highlight the differential functional role of the two families of kinases, and raise the possibility that PI(3)P production by VPS34 may be targeted during the maturation arrest induced by some intracellular parasites.

scholarly journals Digestive Inflammation: Role of Proteolytic Dysregulation

2021 ◽  
Vol 22 (6) ◽  
pp. 2817
Author(s):  
Vincent Mariaule ◽  
Aicha Kriaa ◽  
Souha Soussou ◽  
Soufien Rhimi ◽  
Houda Boudaya ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Inflammatory Response ◽  
Serine Proteases ◽  
Matrix Metalloproteases ◽  
Potential Contribution ◽  
Biological Processes ◽  
Bacterial Origin ◽  
Made In

Dysregulation of the proteolytic balance is often associated with diseases. Serine proteases and matrix metalloproteases are involved in a multitude of biological processes and notably in the inflammatory response. Within the framework of digestive inflammation, several studies have stressed the role of serine proteases and matrix metalloproteases (MMPs) as key actors in its pathogenesis and pointed to the unbalance between these proteases and their respective inhibitors. Substantial efforts have been made in developing new inhibitors, some of which have reached clinical trial phases, notwithstanding that unwanted side effects remain a major issue. However, studies on the proteolytic imbalance and inhibitors conception are directed toward host serine/MMPs proteases revealing a hitherto overlooked factor, the potential contribution of their bacterial counterpart. In this review, we highlight the role of proteolytic imbalance in human digestive inflammation focusing on serine proteases and MMPs and their respective inhibitors considering both host and bacterial origin.

scholarly journals Role of PI3‐kinase in Angiotensin II‐induced Cardiac Hypertrophy: Shift from Class III to Class I

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Tiecheng Zhong ◽  
Lirong Guo ◽  
Stephen T. O'Rourke ◽  
Chengwen Sun
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pi3 Kinase ◽  
Class I ◽  
Class Iii

scholarly journals PERAN PEMBIMBING KEMASYARAKATAN SEBAGAI PENEGAK HUKUM DALAM PENCEGAHAN PENGULANGAN TINDAK PIDANA PADA BALAI PEMASYARAKATAN KELAS 1 MAKASSAR

2021 ◽  
Vol 2 (2) ◽  
pp. 126-130
Author(s):  
I Tri Umbara ◽  
Ruslan Renggong ◽  
Abd. Haris Hamid
Keyword(s):  
Class I ◽  
Normative Approach ◽  
Inhibiting Factors ◽  
Statutory Regulation ◽  
Made In ◽  
Community Counselors

Penelitian ini bertujuan untuk mengetahui peran Pembimbing Kemasyarakatan sebagai penegak hukum dalam melakukan bimbingan terhadap Klien Pemasyarakatan serta mengetahui faktor-faktor penghambat yang dihadapi Pembimbing Kemasyarakatan terkait pelaksanaan tugas dalam hal mencegah pengulangan tindak pidana oleh Klien Pemasyarakatan. Observasi yang dilakukan dalam penelitian ini adalah di Kantor Balai Pemasyarakatan (BAPAS) Kelas I Kota Makassar. Metode yang digunakan penulis adalah pendekatan normatif empiris. Maksudnya pendekatan yang dilakukan untuk menganalisa tentang sejauhmanakah suatu peraturan perundang-undangan atau hukum yang sedang berlaku secara efektif dalam masyarakat mengenai peran Pembimbing Kemasyarakatan sebagai penegak hukum serta mengamati tingkah laku para narapidana dan pembimbing kemasyarakatan di dalam Kantor Balai Pemasyarakatan Kelas I Makassar. Hasil penelitian ini menunjukkan bahwa pelaksanaan peran pembimbing kemasyarakatan sebagai penegak hukum sangat penting dalam pencegahan pengulangan tindak pidana bagi klien yang ditandai dengan berkurangnya jumlah residivis dalam dua tahun terakhir. This study aims to determine the role of Community Supervisors as law enforcers in conducting counseling to Correctional Clients and to find out the inhibiting factors faced by Community Supervisors related to the implementation of tasks in terms of preventing the repetition of criminal acts by Correctional Clients. The observations made in this study were in the Penitentiary Class I Makassar. The method used by the author is an empirical normative approach. The purpose of the approach taken is to analyze the extent to which a statutory regulation or law that is effectively applied in society regarding the role of Community Supervisors as law enforcers as well as observing the behavior of prisoners and community counselors in the Penitentiary Class I Makassar. The results of this study indicate that the implementation of the role of social counselors as law enforcers is very important in preventing the repetition of criminal acts for clients which is marked by the reduced number of recidivists in the last two years.

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