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Topic Review
Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Breast Cancer
Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Adipose tissue is the major microenvironment of breast cancer. Obesity changes the composition, structure, and function of adipose tissue, which is associated with inflammation and metabolic dysfunction. Interestingly, adipose tissue is rich in ASCs/MSCs, and obesity alters the properties and functions of these cells. As a key component of the mammary stroma, ASCs play essential roles in the breast cancer microenvironment. The crosstalk between ASCs and breast cancer cells is multilateral and can occur both directly through cell–cell contact and indirectly via the secretome released by ASC/MSC, which is considered to be the main effector of their supportive, angiogenic, and immunomodulatory functions. 
  • 904
  • 26 Aug 2022
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. 
  • 904
  • 22 Mar 2024
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.
  • 902
  • 28 Oct 2021
Topic Review
Alternative Splicing Mechanisms in Tumors
Alternative pre-mRNA splicing is a process that allows for the generation of an extremely diverse proteome from a much smaller number of genes. In this process, non-coding introns are excised from primary mRNA and coding exons are joined together. Different combinations of exons give rise to alternative versions of a protein.
  • 902
  • 06 Jun 2023
Topic Review
Targeting Cell Surface GRP78 in Cancer
The 78-kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone that plays a crucial role in protein folding homeostasis by regulating the unfolded protein response (UPR). In tumour cells, GRP78 is present at the cell surface, where it functions as a signalling receptor involved in numerous proapoptotic and apoptotic pathways that contribute to cancer cell proliferation and metastasis. As such, novel therapeutic strategies that target cell surface GRP78 in the treatment of several human cancers is highlighted.
  • 901
  • 01 Jul 2022
Topic Review
Therapeutic Implications for Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a type of cancer that arises in the exocrine glands of the pancreas and comprises over 90% of pancreatic malignancies. Currently the 11th most common cancer worldwide, PDAC is the seventh leading cause of cancer-related deaths and is on track to move to second place by 2030. Despite the high prevalence, therapeutic options remain limited, with only modest improvements in overall survival (OS) occurring over the past 50 years.
  • 900
  • 12 Oct 2021
Topic Review
Torsin AAA+ Proteins
Torsin ATPases are members of the AAA+ (ATPases associated with various cellular activities) superfamily of proteins, which participate in essential cellular processes. While AAA+ proteins are ubiquitously expressed and demonstrate distinct subcellular localizations, Torsins are the only AAA+ to reside within the nuclear envelope (NE) and endoplasmic reticulum (ER) network. Moreover, due to the absence of integral catalytic features, Torsins require the NE- and ER-specific regulatory cofactors, lamina-associated polypeptide 1 (LAP1) and luminal domain like LAP1 (LULL1), to efficiently trigger their atypical mode of ATP hydrolysis. Despite their implication in an ever-growing list of diverse processes, the specific contributions of Torsin/cofactor assemblies in maintaining normal cellular physiology remain largely enigmatic. Resolving gaps in the functional and mechanistic principles of Torsins and their cofactors are of considerable medical importance, as aberrant Torsin behavior is the principal cause of the movement disorder DYT1 early-onset dystonia.
  • 899
  • 30 Jun 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. 
  • 898
  • 08 Oct 2022
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.
  • 897
  • 20 Jan 2021
Topic Review
Pseudophosphatases in Disease
Pseudophosphatases are important regulators, and their proper regulation is important for maintaining homeostasis and preventing diseases.
  • 897
  • 14 Jul 2021
Topic Review
Neuronal Autophagy
Autophagy is a major degradative pathway that plays a key role in sustaining cell homeostasis, integrity, and physiological functions. Macroautophagy, which ensures the clearance of cytoplasmic components engulfed in a double-membrane autophagosome that fuses with lysosomes, is orchestrated by a complex cascade of events. Autophagy has a particularly strong impact on the nervous system, and mutations in core components cause numerous neurological diseases. 
  • 897
  • 19 Jan 2024
Topic Review
Stem-Cell-Based Therapy in Alzheimer’s Disease
Stem cells are a versatile source for cell therapy. Their use is particularly significant for the treatment of neurological disorders for which no definitive conventional medical treatment is available. Neurological disorders are of diverse etiology and pathogenesis. Alzheimer’s disease (AD) is caused by abnormal protein deposits, leading to progressive dementia.
  • 896
  • 15 Nov 2022
Topic Review
Golgi Proteostasis
The Golgi apparatus is a central hub for cellular protein trafficking and signaling. Golgi structure and function is tightly coupled and undergoes dynamic changes in health and disease. A crucial requirement for maintaining Golgi homeostasis is the ability of the Golgi to target aberrant, misfolded, or otherwise unwanted proteins to degradation. Recent studies have revealed that the Golgi apparatus may degrade such proteins through autophagy, retrograde trafficking to the ER for ER-associated degradation (ERAD), and locally, through Golgi apparatus-related degradation (GARD).
  • 895
  • 02 Mar 2022
Topic Review
EVs–PEG–cECMH Product
The combination of cardiosphere-derived extracellular vesciles (EVs), polyethylene glycol (PEG), and cardiac extracellular matrix hydrogel (cECMH), EVs–PEG–cECMH, is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.
  • 894
  • 14 Sep 2021
Topic Review
Purinergic Signaling in Colorectal Cancer
Colorectal cancer is a leading cause of cancer-related death. Activated immune cells have the potential to eliminate tumor cells, but cancers gain the ability to suppress immune cell functions and escape immune attack. The researchers explored one mechanism that cancers use to evade immune cells in colorectal cancer. This mechanism alters levels of molecules known as purines. Purines are key players in cellular energetics and many cellular processes and can also lead to immune suppression in cancer.
  • 894
  • 21 Nov 2022
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. 
  • 892
  • 09 Aug 2021
Topic Review
Membrane Lipids in Light-Activation of Drosophila TRP Channels
Transient Receptor Potential (TRP) channels constitute a large superfamily of polymodal channel proteins with diverse roles in many physiological and sensory systems that function both as ionotropic and metabotropic receptors. From the early days of TRP channel discovery, membrane lipids were suggested to play a fundamental role in channel activation and regulation. A prominent example is the Drosophila TRP and TRP-like (TRPL) channels, which are predominantly expressed in the visual system of Drosophila. Light activation of the TRP and TRPL channels, the founding members of the TRP channel superfamily, requires activation of phospholipase Cβ (PLC), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into Diacylglycerol (DAG) and Inositol 1, 4,5-trisphosphate (IP3).
  • 891
  • 19 Apr 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. 
  • 891
  • 02 Apr 2022
Topic Review
Mammalian Circadian Rhythms and Ubiquitin Ligases
Circadian clocks evolved to enable organisms to anticipate and prepare for periodic environmental changes driven by the day–night cycle. This internal timekeeping mechanism is built on autoregulatory transcription–translation feedback loops that control the rhythmic expression of core clock genes and their protein products. The levels of clock proteins rise and ebb throughout a 24-h period through their rhythmic synthesis and destruction. In the ubiquitin–proteasome system, the process of polyubiquitination, or the covalent attachment of a ubiquitin chain, marks a protein for degradation by the 26S proteasome. The process is regulated by E3 ubiquitin ligases, which recognize specific substrates for ubiquitination.
  • 891
  • 21 Sep 2022
Topic Review
Chemokine uptake in Endothelial Cells
The chemokines CCL5 and CXCL4 are deposited by platelets onto endothelial cells, inducing monocyte arrest. Here, the fate of CCL5 and CXCL4 after endothelial deposition was investigated. Human umbilical vein endothelial cells (HUVECs) and EA.hy926 cells were incubated with CCL5 or CXCL4 for up to 120 min, and chemokine uptake was analyzed by microscopy and by ELISA. Intracellular calcium signaling was visualized upon chemokine treatment, and monocyte arrest was evaluated under laminar flow. Whereas CXCL4 remained partly on the cell surface, all of the CCL5 was internalized into endothelial cells. Endocytosis of CCL5 and CXCL4 was shown as a rapid and active process that primarily depended on dynamin, clathrin, and G protein-coupled receptors (GPCRs), but not on surface proteoglycans. Intracellular calcium signals were increased after chemokine treatment. Confocal microscopy and ELISA measurements in cell organelle fractions indicated that both chemokines accumulated in the nucleus. Internalization did not affect leukocyte arrest, as pretreatment of chemokines and subsequent washing did not alter monocyte adhesion to endothelial cells. Endothelial cells rapidly and actively internalize CCL5 and CXCL4 by clathrin and dynamin-dependent endocytosis, where the chemokines appear to be directed to the nucleus. These findings expand our knowledge of how chemokines attract leukocytes to sites of inflammation.
  • 890
  • 22 Sep 2021
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