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Topic Review
Therapeutic Potential of Apoptotic MSCs or MSC-Derived ApoBDs
Mesenchymal stem cells (MSCs) have shown promising therapeutic effects both in preclinical studies (in animal models of a wide range of diseases) and in clinical trials. However, the efficacy of MSC-based therapy is not always predictable. Moreover, despite the large number of studies, the mechanisms underlying the regenerative potential of MSCs are not fully elucidated. It has been reliably established that transplanted MSCs can undergo rapid apoptosis and clearance from the recipient’s body, still exhibiting therapeutic effects, especially those associated with their immunosuppressive/immunomodulating properties. The mechanisms underlying these effects can be mediated by the efferocytosis of apoptotic MSCs by host phagocytic cells.
  • 891
  • 18 Nov 2022
Topic Review
Inhibition of Replication Fork Formation and Progression
Over 1.2 million deaths are attributed to multi-drug-resistant (MDR) bacteria each year. Persistence of MDR bacteria is primarily due to the molecular mechanisms that permit fast replication and rapid evolution. As many pathogens continue to build resistance genes, current antibiotic treatments are being rendered useless and the pool of reliable treatments for many MDR-associated diseases is thus shrinking at an alarming rate. In the development of novel antibiotics, DNA replication initiation and the primosome are still largely underexplored targets.
  • 891
  • 05 Jun 2023
Topic Review
CAR T Cells
Cells are also used as a therapeutic tool. In this type of immunotherapy, the patient’s T cells are genetically engineered ex vivo to express a CAR that recognizes a specific antigen present on the surface of the tumor cells. After reinfusion of these cells in the patient’s circulation, the binding between the CAR T cells and the cancer cells induces a cytotoxic response. One example of this therapy currently being used in clinics is for the treatment of advanced B-cell lymphomas, resulting in complete remission in 30 to 40 % of the patients. Importantly, it needs to be emphasized that CAR T cells are used last in line as a therapeutic strategy to suppress tumor cells. This means that the T cells are often isolated from the patients after various treatments, including chemotherapy that can alter the metabolic phenotype of the T cells (mitochondrial damage and metabolic alterations). Therefore, metabolism is an important aspect in the conception and the anti-tumoral activity of a CAR T cell.
  • 890
  • 29 Mar 2022
Topic Review
IIIG9 in Cancer and Other Pathologies
The identification of new proteins that regulate the function of one of the main cellular phosphatases, protein phosphatase 1 (PP1), is essential to find possible pharmacological targets to alter phosphatase function in various cellular processes, including the initiation and development of multiple diseases. IIIG9 is a regulatory subunit of PP1 initially identified in highly polarized ciliated cells. In addition to its ciliary location in ependymal cells, researchers showed that IIIG9 has extraciliary functions that regulate the integrity of adherens junctions.
  • 888
  • 01 Dec 2022
Topic Review
Rare Neurological Disorders in Zebrafish
Rare diseases are those which affect a small number of people compared to the general population. However, many patients with a rare disease remain undiagnosed, and a large majority of rare diseases still have no form of viable treatment. Approximately 40% of rare diseases include neurologic and neurodevelopmental disorders. In order to understand the characteristics of rare neurological disorders and identify causative genes, various model organisms have been utilized extensively.
  • 888
  • 08 Apr 2022
Topic Review
Pluripotent Stem Cells
Pluripotent stem cells (PSCs) hold great potential both in studies on developmental biology and clinical practice. Mitochondrial metabolism that encompasses pathways that generate ATP and produce ROS significantly differs between PSCs and somatic cells. Correspondingly, for quite a long time it was believed that the redox homeostasis in PSCs is also highly specific due to the hypoxic niche of their origin – within the pre-implantation blastocyst. However, recent research showed that redox parameters of cultivated PSCs have much in common with that of their differentiated progeny cells. Moreover, it has been proven that similar to somatic cells, maintaining the physiological ROS level is critical for the regulation of PSC identity, proliferation, differentiation, and de-differentiation.
  • 886
  • 28 Oct 2021
Topic Review
-Omics Approaches in Studies of Polystyrene MNP Toxicity
The investigation of the toxicity mechanism of micro- and nanoplastics (MNPs) is a topic of major concern for the scientific community. The use of transcriptomics, proteomics, and metabolomics has suggested that the main pathways affected by polystyrene (PS) MNPs are related to energy metabolism, oxidative stress, immune response, and the nervous system, both in fishes and aquatic invertebrates. 
  • 886
  • 22 Mar 2024
Topic Review
Treatment of Intrahepatic Cholangiocarcinoma
Liver metastases are a major management problem; since they occur in tumors of different origin, they are often multiple, difficult to visualize and can lie dormant for many years. Patients with liver metastases usually die of their disease, mostly due to liver failure, since systemic treatments are unable to eradicate micro-metastasis, and interventional loco-regional procedures cannot treat all existing ones. Cholangiocarcinoma (CCA) is the second most common primary liver tumor, showing a poor overall prognosis. When resection is not possible, treatment options include tumor-focused or local ablative therapy, organ-focused or regional therapy and systemic therapy. We reviewed available loco-regional therapeutic options, with particular focus on the CHEMOSAT® Melphalan/Hepatic Delivery System (CS-HDS), which is uniquely positioned to perform a percutaneous hepatic perfusion (PHP), in order to treat the entire liver as a standalone or as complementary therapy. This system isolates the liver circulation, delivers a high concentration of chemotherapy (melphalan), filters most chemotherapy out of the blood and is a repeatable procedure. Most CS-HDS benefits are demonstrated in liver-predominant diseases, like liver metastasis from uveal melanoma (UM), hepatocarcinoma (HCC) and CCA. More than 650 procedures have been performed in Europe to date, mostly to treat liver metastases from UM. In CCA, experience is still limited, but retrospective analyses have been reported, while phase II and III studies are closed, waiting for results or ongoing.
  • 885
  • 20 Jan 2021
Topic Review
Impact of Endoplasmic Reticulum Stress for Type-1-Diabetes
Type-1-diabetes (T1D) is a multifactorial disorder with a global incidence of about 8.4 million individuals in 2021. It is primarily classified as an autoimmune disorder, where the pancreatic β-cells are unable to secrete sufficient insulin. This leads to elevated blood glucose levels (hyperglycemia). The development of T1D is an intricate interplay between various risk factors, such as genetic, environmental, and cellular elements. Here, the focus is on cellular elements such as ER stress leading to defects in insulin secretion and β-cell destruction.
  • 884
  • 03 Nov 2022
Topic Review
Tissue Renin-Angiotensin System
Tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1–7/MasReceptor axis.
  • 883
  • 09 Apr 2021
Topic Review
TP53
TP53 tumor suppressor gene is a key player for cellular homeostasis.
  • 881
  • 02 Feb 2021
Topic Review
GPR15 in Vascular Tissue
GPR15 as a member of the Class A (rhodopsin) orphan G protein-coupled receptor (GPCR) family  has been recently deorphanized by identification of two endogenous receptor-activating ligands in human. Interestingly, in vascular tissue they interact apparently with different cell types. While one ligand triggers a cytoprotective effect on endothelial cells from the luminal site of vessels, the other ligand is rather responsible for the homing of GPR15-expressing lymphocytes into the colon. Thus, in addition to the role of GPR15 as a co-receptor for the human immunodeficiency virus (HIV) or to the expansion of GPR15-expressing lymphocytes in blood by chronic smoking this review will summarize findings to the role of GPR15 for vascular tissue based on new described receptor-ligand interactions.
  • 881
  • 21 Oct 2021
Topic Review
STxB in Mucosal Vaccination
One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells. 
  • 881
  • 25 Mar 2022
Topic Review
Fibrin Glue and MSCs to Regenerate Nerve Injuries
Cell-based therapy is a promising treatment to favor tissue healing through less invasive strategies. Mesenchymal stem cells (MSCs) highlighted as potential candidates due to their angiogenic, anti-apoptotic and immunomodulatory properties, in addition to their ability to differentiate into several specialized cell lines. Cells can be carried through a biological delivery system, such as fibrin glue, which acts as a temporary matrix that favors cell-matrix interactions and allows local and paracrine functions of MSCs. MSCs favored axonal regeneration, remyelination of nerve fibers, as well as promoted an increase in the number of myelinated fibers, myelin sheath thickness, number of axons and expression of growth factors, with significant improvement in motor function recovery. Fibrin glue combined with MSCs has the potential to regenerate nervous system lesions.
  • 880
  • 24 Jan 2022
Topic Review
Aging of Human Hematopoietic Stem and Progenitor Cells
In human blood and immune system, aging is characterized by a decline of innate immunity and regenerative potential of hematopoietic stem cells. This decline is defined at a molecular level in the  hematopoietic stem and progenitor cells (HSPC) compartment. A series of studies have demonstrated that aging of HSPC is induced by an accumulation of senescent cells in the HSPC compartment of the aging human bone marrow. Multi-omics studies have provided evidence that senescent cells are characterized by elevated central carbon metabolism. This property has rendered an enrichment of senescent HSPC for in depth mechanistic studies possible, and in addition has provided novel targets for senolysis therapy strategies. 
  • 880
  • 02 Apr 2022
Topic Review
Aging and Bone Marrow
The aging of bone marrow (BM) remains a very imperative and alluring subject, with an ever-increasing interest among fellow scientists. A considerable amount of progress has been made in this field with the established ‘hallmarks of aging’ and continued efforts to investigate the age-related changes observed within the BM. Inflammaging is considered as a low-grade state of inflammation associated with aging, and whilst the possible mechanisms by which aging occurs are now largely understood, the processes leading to the underlying changes within aged BM remain elusive. The ability to identify these changes and detect such alterations at the genetic level are key to broadening the knowledgebase of aging BM. Next-generation sequencing (NGS) is an important molecular-level application presenting the ability to not only determine genomic base changes but provide transcriptional profiling (RNA-seq), as well as a high-throughput analysis of DNA–protein interactions (ChIP-seq). Utilising NGS to explore the genetic alterations occurring over the aging process within alterative cell types facilitates the comprehension of the molecular and cellular changes influencing the dynamics of aging BM.
  • 878
  • 15 Nov 2021
Topic Review
GPCRs In Intracellular Compartments: Implications For Drug Discovery
The architecture of eukaryotic cells is defined by extensive membrane-delimited compartments, which entails separate metabolic processes that would otherwise interfere with each other, leading to functional differences between cells. G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors, and their signal transduction is traditionally viewed as a chain of events initiated from the plasma membrane. Furthermore, their intracellular trafficking, internalization, and recycling were considered only to regulate receptor desensitization and cell surface expression. On the contrary, accumulating data strongly suggest that GPCRs also signal from intracellular compartments. GPCRs localize in the membranes of endosomes, nucleus, Golgi and endoplasmic reticulum apparatuses, mitochondria, and cell division compartments. Importantly, from these sites they have shown to orchestrate multiple signals that regulate different cell pathways. 
  • 876
  • 08 Oct 2022
Topic Review
Radiotracers Available for Cancer and Disease
Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake.
  • 876
  • 10 Feb 2023
Topic Review
Cytoplasmic Actins in Endothelial Cell
The primary function of the endothelial cells (EC) lining the inner surface of all vessels is to regulate permeability of vascular walls and to control exchange between circulating blood and tissue fluids of organs. The EC actin cytoskeleton plays a crucial role in maintaining endothelial barrier function. Actin cytoskeleton reorganization result in EC contraction and provides a structural basis for the increase in vascular permeability, which is typical for many diseases. Actin cytoskeleton in non-muscle cells presented two actin isoforms: non-muscle β-cytoplasmic and γ-cytoplasmic actins (β-actins and γ-actins), which are encoded by ACTB and ACTG1 genes, respectively. They are ubiquitously expressed in the different cells in vivo and in vitro and the β/γ-actin ratio depends on the cell type. Both cytoplasmic actins are essential for cell survival, but they perform various functions in the interphase and cell division and play different roles in neoplastic transformation. 
  • 875
  • 09 Aug 2021
Topic Review
VAV Proteins
The VAV GEF family has been traditionally linked to protumorigenic actions in cancer. This idea was reinforced by the use of both cancer cell lines and mouse models demonstrating the proactive role of VAV proteins in the development of different types of tumors, such as skin and breast cancer. However, given the presence of structural domains that facilitate the interaction with a large number of protein partners and the particular features of some of the VAV-dependent pathways, it is conceivable that VAV proteins might antagonize cell transformation in certain in vivo contexts.
  • 875
  • 27 Oct 2021
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