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Topic Review
Oxidative Stress and Laminopathies Caused by LMNA Mutations
Mutations in the genes that encode for lamins, predominantly lamin A/C, cause a wide spectrum of human diseases, referred to as laminopathies, including muscular dystrophy, lipodystrophy, and systemic premature aging syndrome. HGPS, one of the most severe laminopathies, is a rare genetic disorder characterized by multisystem abnormalities, including premature aging. The most frequent mutation causing HGPS is c.1842C>T (p.G608G) in exon 11 of LMNA, resulting in cryptic splicing between an abnormal donor site in the middle of exon 11 and the usual acceptor of exon 12. This change causes a 50-amino acid deletion in the carboxyl-terminal tail of prelamin A, producing a truncated protein referred to as progerin. The 50 missing amino acids include the recognition sites for the prelamin A-cleaving enzyme ZMPSTE24. Consequently, progerin is normally farnesylated but cannot be further processed because of the lack of docking sites for ZMPSTE24. The farnesylated domain of progerin is firmly anchored to the nuclear membrane, leading to nuclear deformation and deleterious effects in HGPS cells. Blocking the farnesylation of progerin with a farnesyltransferase inhibitor (FTI) successfully reduced the cytotoxic effects of progerin in vitro; however, a clinical trial of FTIs did not yield promising results. A study showed that the interaction between progerin and wild-type lamin A/C was also a critical cause of nuclear deformation in HGPS and normal aging cells, providing a new therapeutic target for HGPS. Progerin expression in various cell types induces excessive ROS production and reduces the activities of the antioxidant system. Oxidative stress is also implicated in other types of laminopathies, such as Dunnigan-type familial partial lipodystrophy (FPLD), amyotrophic quadricipital syndrome with cardiac involvement, autosomal dominant Emery–Dreifuss muscular dystrophy (AD-EDMD), and restrictive dermopathy (RD).
  • 326
  • 25 May 2023
Topic Review
Beehive Products for Wound Repair and Skin Care
There is a long and interesting history between honeybees and humans. From the beginning, honey has been utilized not only as a sweetener, but also as an ointment and a drug to treat several diseases. Until the discovery of antibiotics, honey was a very popular product used to protect and preserve skin and promote wound healing, to counteract gastrointestinal pains and disorders of the oral cavity, and for other diseases. After the development of antibiotic resistance, honey again gained interest for its use in wound management. Subsequently, more recently, in vitro and in vivo studies have displayed antimicrobial, antioxidant, and other effects of honey and honeybee products, as well as protection of cardiovascular, respiratory, nervous, and gastrointestinal systems. 
  • 326
  • 06 Oct 2023
Topic Review
Microtubule Cytoskeleton Organization, Cell Polarity, and Phosphoinositide Signaling
The capacity for cancer cells to metastasize to distant organs depends on their ability to execute the carefully choreographed processes of cell adhesion and migration. As most human cancers are of epithelial origin (carcinoma), the transcriptional downregulation of adherent/tight junction proteins (e.g., E-cadherin, Claudin and Occludin) with the concomitant gain of adhesive and migratory phenotypes has been extensively studied.
  • 326
  • 09 Oct 2023
Topic Review
Stathmins and Motor Neuron Diseases
Motor neuron diseases (MNDs) are a group of fatal, neurodegenerative disorders with different etiology, clinical course and presentation, caused by the loss of upper and lower motor neurons (MNs). MNs are highly specialized cells equipped with long, axonal processes; axonal defects are some of the main players underlying the pathogenesis of these disorders. Microtubules are key components of the neuronal cytoskeleton characterized by dynamic instability, switching between rapid polymerization and shrinkage. Proteins of the stathmin family affect microtubule dynamics regulating the assembly and the dismantling of tubulin. Stathmin-2 (STMN2) is one of the most abundantly expressed genes in MNs. Following axonal injury, STMN2 expression is upregulated, and the protein is transported toward the growth cones of regenerating axons. STMN2 has a critical role in axonal maintenance, and its dysregulation plays an important role in neurodegenerative processes. Stathmin-1 (STMN1) is a ubiquitous protein that is highly expressed during the development of the nervous system, and its phosphorylation controls microtubule dynamics.
  • 325
  • 01 Apr 2022
Topic Review
Methods to Assess Cell Proliferation in Colorectal Cancer
Colorectal cancer (CRC) is one of the most common and severe malignancies worldwide. Recent advances in diagnostic methods allow for more accurate identification and detection of several molecular biomarkers associated with this cancer. Classical prognostic genetic markers comprise mutations in several genes (e.g., APC, KRAS/BRAF, TGF-β, and TP53). Furthermore, CIN and MSI serve as chromosomal markers, while epigenetic markers include CIMP and many other candidates such as SERP, p14, p16, LINE-1, and RASSF1A. Results on the prognostic value of the most commonly used cell cycle-related markers in CRC demonstrated by immunohistochemical (IHC) methods in relation to patients' overall survival (OS) or disease-free survival (DFS), are inconsistent. However, it was possible to confirm such a role for cyclin B1, cyclin D1, proliferating cell nuclear antigen (PCNA) and Ki-67. The number of long non-coding RNAs (e.g., SNHG1, SNHG6, MALAT-1, CRNDE) and microRNAs (e.g., miR-20a, miR-21, miR-143, miR-145, miR-181a/b) associated with proliferation in CRC as confirmed prognostic markers is increasing. Despite the rather obvious limitations of IHC and new molecular techniques, the standardisation of methods for quantitative assessment of proliferation marker expression, or the understanding of endogenous and exogenous (environmental) mechanisms of accelerated cellular proliferation, requires further development.
  • 325
  • 12 Oct 2023
Topic Review
ROS and Enzymatic Antioxidants in Small Domestic Ruminants
Oxygen is a fundamental element in aerobic life and oxidative metabolism representing the principal energy source for aerobic cells. Reactive oxygen species (ROS) are generated by a variety of cellular metabolic activities and as a by-product of ATP generation mediated by mitochondrial respiration. ROS are engaged in many redox-governing cell activities for the preservation of cellular homeostasis.
  • 324
  • 25 Jul 2023
Topic Review
Racial Disparity in Quadruple Negative Breast Cancer
Black/African-American (AA) women, relative to their White/European-American (EA) counterparts, experience disproportionately high breast cancer mortality. Central to this survival disparity, Black/AA women have an unequal burden of aggressive breast cancer subtypes, such as triple-negative breast cancer (ER/PR-, HER2-wild type; TNBC). Quadruple negative breast cancer (QNBC), a subgroup of triple negative breast cancer, has emerged as a highly aggressive breast cancer subtype that disproportionately afflicts and impacts Black/African-American (AA) women.
  • 323
  • 30 Sep 2022
Topic Review
Ursolic Acid Targets Cancer Hallmarks
Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. 
  • 323
  • 05 Dec 2023
Topic Review
RUNX2 and Cancer
Runt-related transcription factor 2 (RUNX2) is critical for the modulation of chondrocyte osteoblast differentiation and hypertrophy. Recently discovered RUNX2 somatic mutations, expressional signatures of RUNX2 in normal tissues and tumors, and the prognostic and clinical significance of RUNX2 in many types of cancer have attracted attention and led RUNX2 to be considered a biomarker for cancer. Many discoveries have illustrated the indirect and direct biological functions of RUNX2 in orchestrating cancer stemness, cancer metastasis, angiogenesis, proliferation, and chemoresistance to anticancer compounds, warranting further exploration of the associated mechanisms to support the development of a novel therapeutic strategy. 
  • 322
  • 25 Apr 2023
Topic Review
GATNNCDA
Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs with covalent closed loop structure. Researchers have revealed that circRNAs play an important role in human diseases. As experimental identification of interactions between circRNA and disease is time-consuming and expensive, effective computational methods are an urgent need for predicting potential circRNA–disease associations. In this study, we proposed a novel computational method named GATNNCDA, which combines Graph Attention Network (GAT) and multi-layer neural network (NN) to infer disease-related circRNAs. Specially, GATNNCDA first integrates disease semantic similarity, circRNA functional similarity and the respective Gaussian Interaction Profile (GIP) kernel similarities. The integrated similarities are used as initial node features, and then GAT is applied for further feature extraction in the heterogeneous circRNA–disease graph. Finally, the NN-based classifier is introduced for prediction. The results of fivefold cross validation demonstrated that GATNNCDA achieved an average AUC of 0.9613 and AUPR of 0.9433 on the CircR2Disease dataset, and outperformed other state-of-the-art methods.
  • 321
  • 20 Aug 2021
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