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Topic Review
Drug Repositioning of PD-1/PD-L1 Checkpoint
Monoclonal antibodies targeting the PD-1/PD-L1 immune checkpoint have considerably improved the treatment of some cancers, but novel drugs, new combinations, and treatment modalities are needed to reinvigorate immunosurveillance in immune-refractory tumors. An option to elicit antitumor immunity against cancer consists of using approved and marketed drugs known for their capacity to modulate the expression and functioning of the PD-1/PD-L1 checkpoint. Specifically, the repositioning of the approved drugs liothyronine, azelnidipine (and related dihydropyridine calcium channel blockers), niclosamide, albendazole/flubendazole, and a few other modulators of the PD-1/PD-L1 checkpoint (repaglinide, pimozide, fenofibrate, lonazolac, propranolol) is presented. Their capacity to bind to PD-L1 or to repress its expression and function offer novel perspectives for combination with PD-1 targeted biotherapeutics. These known and affordable drugs could be useful to improve the therapy of cancer.
  • 898
  • 22 Jul 2022
Topic Review
Facilitative Sugar Transporters
Facilitative sugar transporters (GLUTs) are passive membrane transporters that are responsible for nearly all of our cells' sugar uptake. They mainly pass glucose and other similar substrates like fructose, mannose, ascorbate, and urate ions. They have been classified into three classes based on structure similarity and substrate affinity.
  • 898
  • 30 Aug 2022
Topic Review
Epithelial Stem Cell Innovation
The field of epithelial stem cell development has been irrevocably shaped by the work of American scientist Howard Green, whose breakthroughs in stem cell culture methods translated to therapeutic practice.
  • 898
  • 20 Mar 2023
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.
  • 897
  • 27 Oct 2021
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.
  • 897
  • 28 Oct 2021
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.
  • 896
  • 05 Jun 2023
Topic Review
Immune System's Role in Liver Biology and Metabolism
The liver is a remarkable organ, which coordinates a multitude of critical functions, whilst retaining the ability to dramatically remodel and regenerate damaged tissue. The liver is composed of four lobes which are subdivided into lobule structures. These are hexagonal in appearance, with each corner displaying the portal triad that consists of the portal vein, bile duct and hepatic artery. Although the liver is an exceptionally regenerative organ, chronic damage may result in scar tissue formation. This does not only have consequences for organ function but is also a major barrier for liver tissue remodeling and regeneration.
  • 895
  • 12 Jun 2023
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.
  • 894
  • 21 Oct 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.
  • 894
  • 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.
  • 893
  • 09 Apr 2021
Topic Review
mtUPR for the Treatment of Mitochondrial Diseases
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich’s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. 
  • 893
  • 19 Dec 2023
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. 
  • 892
  • 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.
  • 890
  • 20 Jan 2021
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.
  • 890
  • 12 Oct 2021
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. 
  • 890
  • 26 Aug 2022
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.
  • 890
  • 15 Nov 2022
Topic Review
AKR1B10 in Physiology and Pathophysiology
AKR1B10 is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the aldo-keto reductase (AKR) 1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α. The enzyme is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. In contrast, AKR1B10 expression is low in other tissues, where the enzyme is upregulated in cancers, as well as in non-alcoholic fatty liver disease and several skin diseases. In addition, the enzyme’s expression is elevated in cancer cells resistant to clinical anti-cancer drugs. Thus, growing evidence supports AKR1B10 as a potential target for diagnosing and treating these diseases. Herein, we reviewed the literature on the roles of AKR1B10 in a healthy gastrointestinal tract, the development and progression of cancers and acquired chemoresistance, in addition to its gene regulation, functions, and inhibitors.
  • 889
  • 24 Jun 2021
Topic Review
Transthyretin: Osteoarticular and Cardiovascular Diseases
Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor.
  • 888
  • 16 Nov 2021
Topic Review
Single-Cell RNA Sequencing in Lymphatic Endothelial Cells
Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. 
  • 888
  • 19 Nov 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. 
  • 888
  • 25 Mar 2022
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