Signaling Role of Pericytes in Vascular Health and Tissue Homeostasis.

Pericytes are multipotent cells embedded within the vascular system, primarily surrounding capillaries and microvessels where they closely interact with endothelial cells. These cells are known for their intriguing properties due to their heterogeneity in tissue distribution, origin, and multifunctional capabilities. Specifically, pericytes are essential in regulating blood flow, promoting angiogenesis, and supporting tissue homeostasis and regeneration. These multifaceted roles draw on pericytes' remarkable ability to respond to biochemical cues, interact with neighboring cells, and adapt to changing environmental conditions. This review aims to summarize existing knowledge on pericytes, emphasizing their versatility and involvement in vascular integrity and tissue health. In particular, a comprehensive view of the major signaling pathways, such as PDGFß/ PDGFRß, TGF-ß, FOXO and VEGF, along with their downstream targets, which coordinate the behavior of pericytes in preserving vascular integrity and promoting tissue regeneration, will be discussed. In this light, a deeper understanding of the complex signaling networks defining the phenotype of pericytes in healthy tissues is crucial for the development of targeted therapies in vascular and degenerative diseases.

Emerging Roles of Phospholipase C Beta Isozymes as Potential Biomarkers in Cardiac Disorders.

Phospholipase C (PLC) enzymes represent crucial participants in the plasma membrane of mammalian cells, including the cardiac sarcolemmal (SL) membrane of cardiomyocytes. They are responsible for the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) into 1,2-diacylglycerol (DAG) and inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), both essential lipid mediators. These second messengers regulate the intracellular calcium (Ca2+) concentration, which activates signal transduction cascades involved in the regulation of cardiomyocyte activity. Of note, emerging evidence suggests that changes in cardiomyocytes' phospholipid profiles are associated with an increased occurrence of cardiovascular diseases, but the underlying mechanisms are still poorly understood. This review aims to provide a comprehensive overview of the significant impact of PLC on the cardiovascular system, encompassing both physiological and pathological conditions. Specifically, it focuses on the relevance of PLCß isoforms as potential cardiac biomarkers, due to their implications for pathological disorders, such as cardiac hypertrophy, diabetic cardiomyopathy, and myocardial ischemia/reperfusion injury. Gaining a deeper understanding of the mechanisms underlying PLCß activation and regulation is crucial for unraveling the complex signaling networks involved in healthy and diseased myocardium. Ultimately, this knowledge holds significant promise for advancing the development of potential therapeutic strategies that can effectively target and address cardiac disorders by focusing on the PLCß subfamily.

Dissecting human anatomy learning process through anatomical education with augmented reality: AEducAR 2.0, an updated interdisciplinary study.

Anatomical education is pivotal for medical students, and innovative technologies like augmented reality (AR) are transforming the field. This study aimed to enhance the interactive features of the AEducAR prototype, an AR tool developed by the University of Bologna, and explore its impact on human anatomy learning process in 130 second-year medical students at the International School of Medicine and Surgery of the University of Bologna. An interdisciplinary team of anatomists, maxillofacial surgeons, biomedical engineers, and educational scientists collaborated to ensure a comprehensive understanding of the study's objectives. Students used the updated version of AEducAR, named AEducAR 2.0, to study three anatomical topics, specifically the orbit zone, facial bones, and mimic muscles. AEducAR 2.0 offered two learning activities: one explorative and one interactive. Following each activity, students took a test to assess learning outcomes. Students also completed an anonymous questionnaire to provide background information and offer their perceptions of the activity. Additionally, 10 students participated in interviews for further insights. The results demonstrated that AEducAR 2.0 effectively facilitated learning and students' engagement. Students totalized high scores in both quizzes and declared to have appreciated the interactive features that were implemented. Moreover, interviews shed light on the interesting topic of blended learning. In particular, the present study suggests that incorporating AR into medical education alongside traditional methods might prove advantageous for students' academic and future professional endeavors. In this light, this study contributes to the growing research emphasizing the potential role of AR in shaping the future of medical education.

Detection of Cancer Stem Cells in Normal and Dysplastic/Leukemic Human Blood.

The hierarchical organization of the leukemic stem cells (LSCs) is identical to that of healthy counterpart cells. It may be split into roughly three stages: a small number of pluripotent stem cells at the top, few lineage-restricted cells in the middle, and several terminally differentiated blood cells at the bottom. Although LSCs can differentiate into the hematopoietic lineage, they can also accumulate as immature progenitor cells, also known as blast cells. Since blast cells are uncommon in healthy bloodstreams, their presence might be a sign of cancer. For instance, a 20% blast cutoff in peripheral blood or bone marrow is formally used to distinguish acute myeloid leukemia from myelodysplastic neoplasms, which is essential to plan the patients' management. Many techniques may be useful for blast enumeration: one of them is flow cytometry, which can perform analyses on many cells by detecting the expression of cell surface markers. Leukemic and non-leukemic blast cells might indeed be characterized by the same surface markers, but these markers are usually differently expressed. Here we propose to use CD45, in combination with CD34 and other cell surface markers, to identify and immunophenotype blast cells in patient-derived samples.

Nuclear Phosphoinositides as Key Determinants of Nuclear Functions.

Polyphosphoinositides (PPIns) are signalling messengers representing less than five per cent of the total phospholipid concentration within the cell. Despite their low concentration, these lipids are critical regulators of various cellular processes, including cell cycle, differentiation, gene transcription, apoptosis and motility. PPIns are generated by the phosphorylation of the inositol head group of phosphatidylinositol (PtdIns). Different pools of PPIns are found at distinct subcellular compartments, which are regulated by an array of kinases, phosphatases and phospholipases. Six of the seven PPIns species have been found in the nucleus, including the nuclear envelope, the nucleoplasm and the nucleolus. The identification and characterisation of PPIns interactor and effector proteins in the nucleus have led to increasing interest in the role of PPIns in nuclear signalling. However, the regulation and functions of PPIns in the nucleus are complex and are still being elucidated. This review summarises our current understanding of the localisation, biogenesis and physiological functions of the different PPIns species in the nucleus.

Lamin B1 as a key modulator of the developing and aging brain.

Lamin B1 is an essential protein of the nuclear lamina that plays a crucial role in nuclear function and organization. It has been demonstrated that lamin B1 is essential for organogenesis and particularly brain development. The important role of lamin B1 in physiological brain development and aging has only recently been at the epicenter of attention and is yet to be fully elucidated. Regarding the development of brain, glial cells that have long been considered as supporting cells to neurons have overturned this representation and current findings have displayed their active roles in neurogenesis and cerebral development. Although lamin B1 has increased levels during the differentiation of the brain cells, during aging these levels drop leading to senescent phenotypes and inciting neurodegenerative disorders such as Alzheimer's and Parkinson's disease. On the other hand, overexpression of lamin B1 leads to the adult-onset neurodegenerative disease known as Autosomal Dominant Leukodystrophy. This review aims at highlighting the importance of balancing lamin B1 levels in glial cells and neurons from brain development to aging.