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Topic Review
Conformationally Constrained Peptides
Constrained Peptides are peptides whose conformation is restricted to the one that the ligand assumes upon target binding (or to a subset of structures occupied by a flexible parent peptide). This is typically achieved by macrocyclization of the peptide chain. Structure regidification is highly advantageous with regard to attaining increased affinity and can also affect proteolytic stability.
  • 1.2K
  • 25 Feb 2021
Topic Review
Peripheral Muscle Fatigue
Muscle fatigue is defined as a decrease in maximal force or power generated in response to contractile activity, and it is a risk factor for the development of musculoskeletal injuries. One of the many stressors imposed on skeletal muscle through exercise is the increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which intensifies as a function of exercise intensity and duration. The progressive reduction in muscle fibers’ ability to generate force originates at different levels of the motor system and can be categorized into two types, namely, central and peripheral fatigue. Peripheral mechanisms of fatigue refer to activity-induced mechanical failure through processes at or distal to neuromuscular junctions, so they can be attributed to neuromuscular transmission and excitation–contraction coupling.
  • 1.2K
  • 10 Mar 2023
Topic Review
Adipogenic Transcription Factors
Adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBPα), C/EBP beta (C/EBPβ) and peroxisome proliferator-associated receptor gamma (PPARγ) are also expressed by osteoclastogenic cells. However, in contrast to MSCs, activation of these adipogenic transcription factors in HSCs promotes the differentiation of osteoclast precursors into mature osteoclasts. Herein, we discuss the molecular mechanisms that link adipogenic transcription factors to the osteoclast differentiation program.
  • 1.2K
  • 28 Oct 2020
Topic Review
Tissue Inhibitor of Metalloproteases 3
The proteolytical cleavage of transmembrane proteins with subsequent release of their extracellular domain, so-called ectodomain shedding, is a post-translational modification that plays an essential role in several biological processes, such as cell communication, adhesion and migration. Metalloproteases are major proteases in ectodomain shedding, especially the disintegrin metalloproteases (ADAMs) and the membrane-type matrix metalloproteases (MT-MMPs), which are considered to be canonical sheddases for their membrane-anchored topology and for the large number of proteins that they can release. The unique ability of tissue inhibitor of metalloproteases 3 (TIMP-3) to inhibit different families of metalloproteases, including the canonical sheddases (ADAMs and MT-MMPs), renders it a master regulator of ectodomain shedding. 
  • 1.2K
  • 16 Mar 2022
Topic Review
IL-10 in Neurodegenerative Diseases
IL-10, an immunosuppressive cytokine, is considered an important anti-inflammatory modulator of glial activation, preventing inflammation-mediated neuronal degeneration under pathological conditions. In this narrative review, we summarize recent insights about the role of IL-10 in the neurodegeneration associated with neuroinflammation, in diseases such as Multiple Sclerosis, Traumatic Brain Injury, Amyotrophic lateral sclerosis, Alzheimer's Disease, and Parkinson's Disease, focusing on the contribution of this cytokine not only in terms of protective action, but also as possibly responsible for clinical worsening. The knowledge of this double face of the same coin, regarding the biological role of the IL-10, could aid the development of targeted therapies useful for limiting neurodegenerative processes.
  • 1.2K
  • 17 Jul 2020
Topic Review
Bisphenol A-Induced Male Infertility
Bisphenol A (BPA) is a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, which negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic-pituitary-gonadal axis and inducing oxidative stress in the testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestradiol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, normal morphology and sperm DNA damage.
  • 1.2K
  • 01 Apr 2021
Topic Review
Vascular Endothelial Glycocalyx
Vascular endothelial cells are a monolayer of cells that comprise the innermost layer of cells in the vascular system, including arteries, veins, and capillaries, and serve a barrier function for the blood vessels surrounding all organs and in direct contact with the blood flowing through the vascular lumen.
  • 1.2K
  • 30 Dec 2020
Topic Review
Modular CAR T Platforms
The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells.
  • 1.2K
  • 25 Feb 2021
Topic Review
Nuclear domains 10 (ND10)
Nuclear domains 10 (ND10), a.k.a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses.
  • 1.2K
  • 25 Mar 2021
Topic Review
Casein Kinase 1α
Wnt signaling regulates numerous cellular processes during embryonic development and adult tissue homeostasis. Underscoring this physiological importance, deregulation of the Wnt signaling pathway is associated with many disease states, including cancer. Here, we review pivotal regulatory events in the Wnt signaling pathway that drive cancer growth. We then discuss the roles of the established negative Wnt regulator, casein kinase 1α (CK1α), in Wnt signaling. Although the study of CK1α has been ongoing for several decades, the bulk of such research has focused on how it phosphorylates and regulates its various substrates. We focus here on what is known about the mechanisms controlling CK1α, including its putative regulatory proteins and alternative splicing variants. Finally, we describe the discovery and validation of a family of pharmacological CK1α activators capable of inhibiting Wnt pathway activity. One of the important advantages of CK1α activators, relative to other classes of Wnt inhibitors, is their reduced on-target toxicity, overcoming one of the major impediments to developing a clinically relevant Wnt inhibitor. Therefore, we also discuss mechanisms that regulate CK1α steady-state homeostasis, which may contribute to the deregulation of Wnt pathway activity in cancer and underlie the enhanced therapeutic index of CK1α activators. 
  • 1.2K
  • 26 Oct 2020
Topic Review
Mitochondrial Carriers
Mitochondrial carriers play a fundamental role in cellular metabolism, connecting mitochondrial with cytosolic reactions. By transporting substrates across the inner membrane of mitochondria, they contribute to many processes that are central to cellular function. The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, most of which have been functionally characterized.
  • 1.2K
  • 23 Sep 2021
Topic Review
Endogenous Opioid Peptides
There exist three main types of endogenous opioid peptides, enkephalins, dynorphins and β-endorphin, all of which are derived from their precursors. These endogenous opioid peptides act through opioid receptors, including mu opioid receptor (MOR), delta opioid receptor (DOR) and kappa opioid receptor (KOR), and play important roles not only in analgesia, but also many other biological processes such as reward, stress response, feeding and emotion. 
  • 1.2K
  • 08 May 2021
Topic Review
The Mitochondrial Genome
Mitochondria are powerhouses of the cell and implement oxidative phosphorylation processes. Similar to plastids, mitochondria are endosymbionts of a pro-eukaryotic cell, have their own genome, and their own transcriptional and translational machinery.
  • 1.2K
  • 12 Jan 2023
Topic Review
Molecular Progression of Prostate Cancer
We have witnessed noteworthy progress in our understanding of prostate cancer over the past decades. This basic knowledge has been translated into efficient diagnostic and treatment approaches leading to the improvement in patient survival. However, the molecular pathogenesis of prostate cancer appears to be complex, and histological findings often do not provide an accurate assessment of disease aggressiveness and future course. Moreover, we also witness tremendous racial disparity in prostate cancer incidence and clinical outcomes necessitating a deeper understanding of molecular and mechanistic bases of prostate cancer. Biological research heavily relies on model systems that can be easily manipulated and tested under a controlled experimental environment. Over the years, several cancer cell lines have been developed representing diverse molecular subtypes of prostate cancer. In addition, several animal models have been developed to demonstrate the etiological molecular basis of the prostate cancer. In recent years, patient-derived xenograft and 3-D culture models have also been created and utilized in preclinical research. This review is an attempt to succinctly discuss existing information on the cellular and molecular progression of prostate cancer. We also discuss available model systems and their tested and potential utility in basic and preclinical prostate cancer research.
  • 1.2K
  • 24 Sep 2020
Topic Review
TGF-β Signaling in Tumor Microenvironment
Transforming growth factor-β (TGF-β) signaling triggers diverse biological actions in inflammatory diseases. In tissue fibrosis, it acts as a key pathogenic regulator for promoting immunoregulation via controlling the activation, proliferation, and apoptosis of immunocytes. In cancer, it plays a critical role in tumor microenvironment (TME) for accelerating invasion, metastasis, angiogenesis, and immunosuppression. Increasing evidence suggest a pleiotropic nature of TGF-β signaling as a critical pathway for generating fibrotic TME, which contains numerous cancer-associated fibroblasts, extracellular matrix proteins, and remodeling enzymes. Better understanding the underlying mechanisms may uncover novel therapeutic targets for cancer.
  • 1.2K
  • 28 Jul 2021
Topic Review
Plasmid DNA for Therapeutic Applications in Cancer
Plasmid DNA can be developed to treat different diseases, such as infections and cancer. In most cancers, the immune system is limited or suppressed, allowing cancer cells to grow. DNA vaccination has demonstrated its capacity to stimulate the immune system to fight against cancer cells.
  • 1.2K
  • 15 Sep 2022
Topic Review
Natural Compounds in Thromboembolism Treatment
Venous thromboembolism (VTE) refers to deep vein thrombosis (DVT), whose consequence may be a pulmonary embolism (PE). Thrombosis is associated with significant morbidity and mortality and is the third most common cardiovascular disease after myocardial infarction and stroke. DVT is associated with the formation of a blood clot in a deep vein in the body. Thrombosis promotes slowed blood flow, hypoxia, cell activation, and the associated release of many active substances involved in blood clot formation. All thrombi which adhere to endothelium consist of fibrin, platelets, and trapped red and white blood cells.
  • 1.2K
  • 11 Nov 2020
Topic Review
Microbial Enzyme Applied to Plastic Depolymerization
The accumulation of synthetic plastic waste in the environment has become a global concern. Microbial enzymes (purified or as whole-cell biocatalysts) represent emerging biotechnological tools for waste circularity; they can depolymerize materials into reusable building blocks, but their contribution must be considered within the context of present waste management practices. 
  • 1.2K
  • 28 Feb 2023
Topic Review
NMR-Based Metabolomics in Metal-Based Drug Research
Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. Due to the low work-up required, high data reproducibility, and high throughput, NMR spectroscopy is an optimal detection technique in metabolomics studies.  The use of NMR-based metabolomic approaches in the investigation of a metal drug action mechanism or for assessing tumour response to anticancer metal agents is a recent, fast-growing tool. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. The future perspectives are even more interesting.  The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments. Moreover, NMR-based metabolomics could also play an important role in clinical trials, preventing or reducing unwanted side effects of metal anticancer drugs by the early detection of metabolic dysfunctions in bio-fluids. 
  • 1.2K
  • 15 Feb 2021
Topic Review
Combining Experimental and Computational Methods
The integration of experimental and computational methods can assist and enrich the interpretation of the experimental results, providing new detailed molecular understanding of the systems.
  • 1.2K
  • 14 Jan 2021
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