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Topic Review
Human PCNA
Proliferating cell nuclear antigen (PCNA) is an essential factor in DNA replication and repair. It forms a homotrimeric ring that embraces the DNA and slides along it, anchoring DNA polymerases and other DNA editing enzymes. It also interacts with regulatory proteins through a sequence motif known as PCNA Interacting Protein box (PIP-box). We here review the latest contributions to knowledge regarding the structure-function relationships in human PCNA, particularly the mechanism of sliding, and of the molecular recognition of canonical and non-canonical PIP motifs. The unique binding mode of the oncogene p15 is described in detail, and the implications of the recently discovered structure of PCNA bound to polymerase δ are discussed. The study of the post-translational modifications of PCNA and its partners may yield therapeutic opportunities in cancer treatment, in addition to illuminating the way PCNA coordinates the dynamic exchange of its many partners in DNA replication and repair.
  • 790
  • 08 Jun 2021
Topic Review
Functional Nanomaterials in Visualization of Cardiovascular Injury
Acute myocardial infarction is a major global health problem, and the repair of damaged myocardium is still a major challenge. Myocardial injury triggers an inflammatory response: immune cells infiltrate into the myocardium while activating myofibroblasts and vascular endothelial cells, promoting tissue repair and scar formation. Fragments released by cardiomyocytes become endogenous “danger signals”, which are recognized by cardiac pattern recognition receptors, activate resident cardiac immune cells, release thrombin factors and inflammatory mediators, and trigger severe inflammatory responses. Inflammatory signaling plays an important role in the dilation and fibrosis remodeling of the infarcted heart, and is a key event driving the pathogenesis of post-infarct heart failure. At present, there is no effective way to reverse the inflammatory microenvironment in injured myocardium, so it is urgent to find new therapeutic and diagnostic strategies. Nanomedicine, the application of nanoparticles for the prevention, treatment, and imaging of disease, has produced a number of promising applications. 
  • 789
  • 24 Apr 2022
Topic Review
The Phenomenon of Ash Dieback
Common ash F. excelsior is a species with demanding soil requirements, needing fertile, moist sites with neutral pH. For many years, common ash was considered a species resistant to diseases, including pathogenic oomycetes of the genus Phytophthora. 
  • 789
  • 15 Nov 2023
Topic Review
Modeling of Old Scars
Severe skin scars (i.e., hypertrophic and keloid) induce physical and emotional discomfort and functional disorders such as contractures and body part deformations. Scar’s response to treatment depends on “maturity”, which increases with time but is not merely proportional to it. When “fresh”, scars are relatively more treatable by conservative methods, while the treatment is only partially efficient. In contrast, surgery is a preferred approach for the older scars, but it is associated with a risk of the scar regrowth and worsening after excision if unrecognized immature scar tissue remains in the operated lesion. Therefore, to develop better treatment and diagnostics of scars, understanding of the scar maturation is essential. This requires biologically accurate experimental models of skin scarring. The current models only mimic the early stages of skin scar development. They are useful for testing new scar-preventing approaches while not addressing the problem of the older scars that exist for years. 
  • 788
  • 20 Apr 2021
Topic Review
Gene-Editing Technology of Zebrafish
As a vertebrate model, zebrafish (Danio rerio) plays a vital role in the field of life sciences. Recently, gene-editing technology has become increasingly innovative, significantly promoting scientific research on zebrafish. However, the implementation of these methods in a reasonable and accurate manner to achieve efficient gene-editing remains challenging.
  • 787
  • 08 Sep 2021
Topic Review
Wet Stormwater Ponds
Stormwater ponds, especially wet stormwater ponds, are a common way to handle stormwater and are used to retain pollutants through sedimentation. The ponds resemble small natural lakes and will be colonized by flora and fauna.
  • 784
  • 10 Nov 2021
Topic Review
TP53 in Germ Cell Tumours
The cure rate of germ cell tumours (GCTs) has significantly increased from the late 1970s since the introduction of cisplatin-based therapy. The exquisite cisplatin sensitivity has been mainly explained by the over-expression in GCTs of wild-type TP53 protein and the lack of TP53 somatic mutations; however, several other mechanisms seem to be involved, many of which remain still elusive. The findings about the role of TP53 in platinum-sensitivity and resistance, as well as the reported evidence of second cancers (SCs) in GCT patients treated only with surgery, suggesting a spectrum of cancer predisposing syndromes, highlight the need for a deepened understanding of the role of TP53 in GCTs. 
  • 783
  • 27 Jul 2021
Topic Review
Histone Modifiers and p53 in Regulating Gene Expression
Chromatin structure plays a fundamental role in regulating gene expression, with histone modifiers shaping the structure of chromatin by adding or removing chemical changes to histone proteins. The p53 transcription factor controls gene expression, binds target genes, and regulates their activity. While p53 has been extensively studied in cancer research, specifically in relation to fundamental cellular processes, including gene transcription, apoptosis, and cell cycle progression, its association with histone modifiers has received limited attention.  
  • 782
  • 24 Jul 2023
Topic Review
Effects of Melatonin on Cryopreservation-Induced Oxidative Stress
It is widely accepted that oxidative stress (OS) coming from a wide variety of causes has detrimental effects on male fertility. Antioxidants could have a significant role in the treatment of male infertility, and the systematic research on the role of melatonin to ameliorate OS clearly shows that improvement of semen parameters follows melatonin supplementation.
  • 780
  • 18 Oct 2023
Topic Review
B Cells and B-Cell Receptor Signaling
B-cell receptor (BCR) is a B cell hallmark surface complex regulating multiple cellular processes in normal as well as malignant B cells. Igα (CD79a)/Igβ (CD79b) are essential components of BCR that are indispensable for its functionality, signal initiation, and signal transduction. CD79a/CD79b-mediated BCR signaling is required for the survival of normal as well as malignant B cells via a wide signaling network. Studies identified the great complexity of this signaling network and revealed the emerging role of CD79a/CD79b in signal integration.
  • 780
  • 09 Jan 2024
Topic Review
Upper Motor Neuron Disorders
Following the exclusion of potentially reversible causes, the differential for those patients presenting with a predominant upper motor neuron syndrome includes primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), or upper motor neuron dominant ALS (UMNdALS). Differentiation of these disorders in the early phases of disease remains challenging. While no single clinical or diagnostic tests is specific, there are several developing biomarkers and neuroimaging technologies which may help distinguish PLS from HSP and UMNdALS. Recent consensus diagnostic criteria and use of evolving technologies will allow more precise delineation of PLS from other upper motor neuron disorders and aid in the targeting of potentially disease-modifying therapeutics. 
  • 779
  • 19 May 2021
Topic Review
3D Tumor Spheroid to Model Tumor Microenvironment
The tumor microenvironment (TME) is a complex and dynamic entity composed of malignant and non-malignant cells, including innate and adaptive immune cells, fibroblasts, adipocytes, vascular and lymphatic endothelial cells, pericytes, and the extracellular matrix (ECM).  Both the physical and biochemical features of the tumor microenvironment (TME) play a critical role in promoting the differentiation, proliferation, invasion, and metastasis of cancer cells. It is therefore essential to understand how malignant cells interact and communicate with an assortment of supportive tumor-associated cells including macrophages, fibroblasts, endothelial cells, and other immune cells. To study the complex mechanisms behind cancer progression, 3D spheroid and organoid models are widely in favor because they replicate the stromal environment and multicellular structure present within an in vivo tumor. It provides more precise data about the cell–cell interactions, tumor characteristics, drug discovery, and metabolic profile of cancer cells compared to oversimplified 2D systems and unrepresentative animal models. 
  • 776
  • 01 Mar 2023
Topic Review
Neuropathological Hallmarks of Alzheimer’s Disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to dementia and patient death. AD is characterized by intracellular neurofibrillary tangles, extracellular amyloid beta (Aβ) plaque deposition, and neurodegeneration. Diverse alterations have been associated with AD progression, including genetic mutations, neuroinflammation, blood–brain barrier (BBB) impairment, mitochondrial dysfunction, oxidative stress, and metal ion imbalance
  • 775
  • 22 May 2023
Topic Review
Selective Vulnerability to Neurodegenerative Disease
Neurodegenerative diseases (NDs) manifest a wide variety of clinical symptoms depending on the affected brain regions. Gaining insights into why certain regions are resistant while others are susceptible is vital for advancing therapeutic strategies. While gene expression changes offer clues about disease responses across brain regions, the mixture of cell types therein obscures experimental results. 
  • 774
  • 23 Feb 2024
Topic Review
Mammalian Extracellular Matrix and Microgravity
The extracellular matrix (ECM) is a constituent of all tissues, representing an integrating network that consists of specific and similar attributes. The ECM always includes collagen and noncollagen proteins, glycoproteins, and proteoglycans. The molecular composition of these structures demonstrates a huge diversity determined by the functional needs of a particular tissue. Meanwhile, it is the structural uniformity that ensures the operation of the ECM as a putative gravity detector. It is reasonable to assume that ECM components can act as an extracellular “mechanical sensor”.
  • 773
  • 14 Sep 2022
Topic Review
Mitochondrial Management of Reactive Oxygen Species
Mitochondria in aerobic eukaryotic cells are both the site of energy production and the formation of harmful species, such as radicals and other reactive oxygen species, known as ROS. They contain an efficient antioxidant system, including low-molecular-mass molecules and enzymes that specialize in removing various types of ROS or repairing the oxidative damage of biological molecules. Under normal conditions, ROS production is low, and mitochondria, which are their primary target, are slightly damaged in a similar way to other cellular compartments, since the ROS released by the mitochondria into the cytosol are negligible. As the mitochondrial generation of ROS increases, they can deactivate components of the respiratory chain and enzymes of the Krebs cycle, and mitochondria release a high amount of ROS that damage cellular structures.
  • 771
  • 03 Dec 2021
Topic Review
Gastric Stump Cancer after Partial Gastrectomy
Distal gastrectomy for benign gastroduodenal peptic disease has become rare, but it still represents a widely adopted procedure for advanced and, in some countries, even for early distal gastric cancer.
  • 771
  • 25 Mar 2022
Topic Review
Extracellular Vesicles and Cancer Therapy
Oxidative stress plays a significant role in cancer development and cancer therapy, and is a major contributor to normal tissue injury. The unique characteristics of extracellular vesicles (EVs) have made them potentially useful as a diagnostic tool in that their molecular content indicates their cell of origin and their lipid membrane protects the content from enzymatic degradation. In addition to their possible use as a diagnostic tool, their role in how normal and diseased cells communicate is of high research interest. The most exciting area is the association of EVs, oxidative stress, and pathogenesis of numerous diseases. 
  • 770
  • 01 Jul 2022
Topic Review
Biological Alterations Underlying Suicidal Behaviour
Suicidal behaviour is a complex, multi-factorial, polygenic and independent mental health problem caused by a combination of alterations and dysfunctions of several biological pathways and disruption of normal mechanisms in brain regions that remain poorly understood and need further investigation to be deciphered. Suicide complexity and unpredictability gained international interest as a field of research. Several studies have been conducted at the neuropathological, inflammatory, genetic, and molecular levels to uncover the triggers behind suicidal behaviour and develop convenient and effective therapeutic or at least preventive procedures.
  • 770
  • 03 Apr 2023
Topic Review
S-100 Proteins
S100s are a group of calcium-binding proteins which received this name because of their solubility in a 100% saturated solution of ammonium sulphate at neutral pH. All members of the S100 protein family have a similar molecular mass of 10–12 KDa, and they each share 25–65% similarity in their amino acid sequence.
  • 769
  • 03 Jul 2023
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