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Topic Review
Enteric Glial Cells and Their Involvement in PD
The brain–gut axis has been identified as an important contributor to the physiopathology of Parkinson’s disease (PD).  In this pathology, inflammation is thought to be driven by the damage caused by aggregation of α-synuclein in the brain. Activation and reactive gliosis are associated to the neurodegeneration produced by Parkinson’s disease in the enteric nervous system.
  • 520
  • 26 Jan 2024
Topic Review
Extracellular Vesicles in the Central Nervous System
Communication in the central nervous system (CNS) is fundamental for different biological functions including brain development, homeostasis preservation, and neural circuit formation. Indeed, the crosstalk between glia and neurons is critical in the CNS for a variety of biological functions, such as brain development, neural circuit maturation, and homeostasis maintenance. Glia cells are involved in different processes including inflammatory responses to infections or diseases, neurotrophic support, and synaptic remodelling and pruning. In addition to the traditional direct cell-to-cell contact, glial cell can also communicate with neurons through the paracrine action of secreted molecules, or by the release and reception of extracellular vesicles (EVs). EVs, which are subdivided into three subtypes: microvesicles, exosomes, and apoptotic bodies, are a major constituent of the cell secretome. EVs have the ability to circulate in the extracellular body fluid and modulate several biological processes and their associated pathways. EVs cross the blood–brain barrier (BBB) bidirectionally from the bloodstream to the brain parenchyma and vice versa. They play an important role in brain–periphery communication in physiology and pathophysiology. According to the current literature, although EVs cross the BBB, it is unclear how, where, and when they can overcome this tightly controlled cellular barrier.
  • 517
  • 30 Jan 2024
Topic Review
PTHrP-Related Signatures in Adipogenesis and Transdifferentiation
Parathyroid-hormone-related protein (PTHrP) is a protein hormone of 139, 141, or 173 amino acids, which may be cleaved into smaller bioactive forms, comprising amino terminus, mid-region, and carboxy terminus peptides, active as key controllers of viability, proliferation, and differentiation in diverse normal and pathological cell and tissue model systems via the reprogramming of gene expression and intracellular signalization.
  • 514
  • 12 Jul 2023
Topic Review
Getting Sugar Coating Right—Role of Golgi Trafficking Machinery
The Golgi is the central organelle of the secretory pathway and it houses the majority of the glycosylation machinery, which includes glycosylation enzymes and sugar transporters. Correct compartmentalization of the glycosylation machinery is achieved by retrograde vesicular trafficking as the secretory cargo moves forward by cisternal maturation. The vesicular trafficking machinery which includes vesicular coats, small GTPases, tethers and SNAREs, play a major role in coordinating the Golgi trafficking thereby achieving Golgi homeostasis. Glycosylation is a template-independent process, so its fidelity heavily relies on appropriate localization of the glycosylation machinery and Golgi homeostasis. Mutations in the glycosylation enzymes, sugar transporters, Golgi ion channels and several vesicle tethering factors cause congenital disorders of glycosylation (CDG) which encompass a group of multisystem disorders with varying severities.
  • 511
  • 31 Mar 2023
Topic Review
Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma
Cholangiocarcinoma (CCA) is a fatal tumor, accounting for 2% of all cancer-related mortalities worldwide yearly due to its high aggressiveness and poor response to current therapies. Furthermore, over the past few decades, CCA mortality has increased globally.
  • 511
  • 12 Jan 2024
Topic Review
Inflammatory Burden and Immunomodulative Therapeutics of Cardiovascular Diseases
Besides traditional risk factors, accumulated evidence suggested that a high inflammatory burden has emerged as a key characteristic modulating both the pathogenesis and progression of cardiovascular diseases, inclusive of atherosclerosis and myocardial infarction. To mechanistically elucidate the correlation, signalling pathways downstream to Toll-like receptors, nucleotide oligomerisation domain-like receptors, interleukins, tumour necrosis factor, and corresponding cytokines were raised as central mechanisms exerting the effect of inflammation. Other remarkable adjuvant factors include oxidative stress and secondary ferroptosis. These molecular discoveries have propelled pharmaceutical advancements. Statin was suggested to confer cardiovascular benefits not only by lowering cholesterol levels but also by attenuating inflammation. Colchicine was repurposed as an immunomodulator co-administered with coronary intervention. Novel interleukin-1β and −6 antagonists exhibited promising cardiac benefits in the recent trials as well. Moreover, manipulation of gut microbiota and associated metabolites was addressed to antagonise inflammation-related cardiovascular pathophysiology. The gut-cardio-renal axis was therein established to explain the mutual interrelationship.
  • 509
  • 29 Jan 2022
Topic Review
Dental Follicle Cells Driving Osteogenic Differentiation
When research on osteogenic differentiation in dental follicle cells (DFCs) began, projects focused on bone morphogenetic protein (BMP) signaling. The BMP pathway induces the transcription factor DLX3, whichh in turn induces the BMP signaling pathway via a positive feedback mechanism. However, this BMP2/DLX3 signaling pathway only seems to support the early phase of osteogenic differentiation, since simultaneous induction of BMP2 or DLX3 does not further promote differentiation. Data showed that inhibition of classical protein kinase C (PKCs) supports the mineralization of DFCs and that osteogenic differentiation is sensitive to changes in signaling pathways, such as protein kinase B (PKB), also known as AKT. Small changes in the lipidome seem to confirm the participation of AKT and PKC in osteogenic differentiation. 
  • 508
  • 01 Nov 2023
Topic Review
Autophagy in Cardiac Differentiation
Autophagy is a critical biological process in which cytoplasmic components are sequestered in autophagosomes and degraded in lysosomes. This highly conserved pathway controls intracellular recycling and is required for cellular homeostasis, as well as the correct functioning of a variety of cellular differentiation programs, including cardiomyocyte differentiation. By decreasing oxidative stress and promoting energy balance, autophagy is triggered during differentiation to carry out essential cellular remodeling, such as protein turnover and lysosomal degradation of organelles. When it comes to controlling cardiac differentiation, the crosstalk between autophagy and other signaling networks such as fibroblast growth factor (FGF), Wnt, Notch, and bone morphogenetic proteins (BMPs) is essential, yet the interaction between autophagy and epigenetic controls remains poorly understood. Numerous studies have shown that modulating autophagy and precisely regulating it can improve cardiac differentiation, which can serve as a viable strategy for generating mature cardiac cells. 
  • 507
  • 07 Jul 2023
Topic Review
3D Culture Models of Exosomes in Breast Cancer
Breast cancer comes in different types, making it hard to treat effectively. One particularly aggressive type, called triple-negative breast cancer, is tough to target with current treatments. Scientists use advanced methods like 3D cultures, which mimic human tissue better than traditional lab methods, to study breast cancer. These 3D cultures help understand how tiny communication structures called exosomes affect cancer growth, spread, and response to therapy. Exosomes are like messengers between cells and can influence cancer’s behavior and response to therapy.
  • 506
  • 28 Feb 2024
Topic Review
EMP/EMT-Dependent Fibrosis
Fibrosis represents a process characterized by excessive deposition of extracellular matrix (ECM) proteins. It often represents the evolution of pathological conditions, causes organ failure, and can, in extreme cases, compromise the functionality of organs to the point of causing death.
  • 504
  • 08 Mar 2024
Topic Review
Influence of Extracellular Vesicles on Lung Stromal Components
One of the common locations for breast cancer metastasis is the lung, which is associated with significant morbidity and mortality. Several studies have demonstrated that breast cancer-derived extracellular vesicles secreted from the primary breast tumor play a key role in establishing the lung pre-metastatic niche to support colonization of metastatic tumor cells. 
  • 503
  • 27 Jul 2023
Topic Review
Oligodendroglial Epigenetics
Oligodendroglial cells are the myelinating cells of the central nervous system. From neural stem cells to mature oligodendrocytes, their specification and then differentiation are regulated by the dynamic expression of transcription factors, which control the expression of lineage-specific genes (e.g., Ascl1, Olig1, Sox10) or myelinating genes (e.g., Yy1, Myrf). While these transcriptional events are tightly orchestrated, environmental cues are also critical in this process. The integration of external cues, such as neuronal activity, into intrinsic signals is mediated by epigenetic modifications, which are known to control chromatin organization and, in turn, regulate gene expression. In particular, chromatin condensation and accessibility are regulated by DNA methylation, histone modifications, and chromatin remodelers, which interact with long non-coding RNA (lncRNA) and microRNA (miRNA), as well as nuclear organization via lamins. Recently, the methylation of mRNA has also been described as an epigenetic modification, resulting in gene expression regulation at the translational level.
  • 498
  • 04 Mar 2021
Topic Review
Receptor Complexes Involving Dopamine Receptors
Dopamine (DA) is a catecholamine, that is, an ethylamine with an attached catechol group (a phenyl group with two hydroxyl groups in meta- and para positions). DA-producing neurons were first identified and mapped in animals by Dahlström and Fuxe in 1964, indicating the existence of neuronal circuits using DA as a neurotransmitter.
  • 496
  • 11 Oct 2023
Topic Review
Marginal Zone Precursor-Like in the Context of HIV
Marginal zone (MZ) B-cells are innate-like, and possess a polyreactive B-cell receptor (BCR) and several pattern recognition receptors (PRR) [1,2]. They are known to generate low-affinity first-line antibody responses against invading pathogens such as encapsulated bacteria.
  • 486
  • 18 Apr 2022
Topic Review
The Interaction between Melanoma Cells and Tumor Microenvironment
Malignant melanoma is a very aggressive skin cancer, characterized by a heterogeneous nature and high metastatic potential. The incidence of melanoma is continuously increasing worldwide, and it is one of the most common cancers in young adults. The understanding of melanoma biology has increased profoundly, and disease management for patients with disseminated disease has improved due to the emergence of immunotherapy and targeted therapy. However, a significant fraction of patients relapse or do not respond adequately to treatment. This can partly be explained by the complex signaling between the tumor and its microenvironment, giving rise to melanoma phenotypes with different patterns of disease progression.
  • 486
  • 06 Oct 2023
Topic Review
EVs’ Mechanisms of HSP Transmission among TME Cells
From an evolutive perspective, tumor cells endure successive turnover upon stress conditions and pressure to adapt to new environments. These cells use exceptional communication skills to share biological information to “survive upon every metabolic cost”. The tumor microenvironment (TME) is a miscellaneous collection of cells, factors, and extracellular vesicles (EVs). EVs are small lipid bilayer-delimited particles derived from cells with sizes ranging from 100 to 1000 nm. Exosomes (<160 nm) are the minor subtype of EVs, originating from the endosomal pathways. The TME also contains “giant” vesicles, microvesicles (100–1000 nm, MV), originated from membrane blebbing. EVs can act as intercellular communication mediators, contributing to many biological processes, by carrying different biomolecules, such as proteins, lipids, nucleic acids, and metabolites. EV secretion can promote either tumor cell survival or manage their stress to death. Tumor-derived EVs transfer adaptative stress signaling to recipient cells, reprograming these cells. Heat shock proteins (HSP) are prominent stress response regulators, specifically carried by exosomes. HSP-loaded EVs reprogram tumor and TME cells to acquire mechanisms contributing to tumor progression and therapy resistance. The intercellular communication mediated by HSP-loaded EVs favors the escape of tumor cells from the endoplasmic reticulum stress, hypoxia, apoptosis, and anticancer therapies. Extracellular HSPs activate and deactivate the immune response, induce cell differentiation, change vascular homeostasis, and help to augment the pre-metastatic niche formation.
  • 486
  • 18 Jan 2024
Topic Review
P2X7R and Microglia
P2X receptors are a family of seven ATP-gated ion channels that trigger physiological and pathophysiological responses in various cells. Five of the family members are sensitive to low concentrations of extracellular ATP, while the P2X6 receptor has an unknown affinity. The last subtype, the P2X7 receptor, is unique in requiring millimolar concentrations to activate in humans fully. This low sensitivity imparts the agonist with the ability to act as a damage-associated molecular pattern that triggers the innate immune response in response to the elevated extracellular ATP levels accompanying inflammation and tissue damage.
  • 486
  • 29 Jan 2024
Topic Review
Diagnosis and Treatment of Endometrial Cancer
The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost–benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of The Cancer Genome Atlas (TCGA) provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient’s needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies.
  • 481
  • 27 Jun 2023
Topic Review
Cell Death Pathways in Oral Cancer
Oral squamous cell carcinoma (OSCC) is the most common and lethal type of head and neck cancer in the world. Variable response and acquisition of resistance to traditional therapies show that it is essential to develop novel strategies that can provide better outcomes for the patient. Activation of cell death pathways, such as the emerging forms of non-apoptotic programmed cell death, including ferroptosis, pyroptosis, necroptosis, NETosis, parthanatos, mitoptosis and paraptosis, may represent clinically relevant novel therapeutic opportunities. 
  • 478
  • 29 Feb 2024
Topic Review
Vitamin D and Resveratrol Performances in COVID-19
A variety of observational epidemiological studies have reported that vitamin D deficiency is often a crucial factor in many inflammatory diseases and autoimmune diseases, as well as the susceptibility to contract infectious diseases, including acute respiratory infections. Similarly, resveratrol regulates immunity, modifying the gene expression and the release of proinflammatory cytokines in the immune cells. Therefore, it plays an immunomodulatory role that can be beneficial in the prevention and development of non-communicable diseases associated with inflammation. Since both vitamin D and resveratrol also act as immunomodulators in inflammatory pathologies, many studies have paid particular attention to an integrated treatment of either vitamin D or resveratrol in the immune reaction against SARS-CoV-2 infections.
  • 477
  • 28 Jun 2023
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