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Topic Review
Heroin Regulates Orbitofrontal Circular RNAs
The number of drug overdose deaths involving opioids continues to rise in the United States. Many patients with opioid use disorder (OUD) that seek treatment still experience relapse. Perseverant opioid seeking behaviors represent a major challenge to treating OUD and additional therapeutic development will require insight into opioid-induced neurobiological adaptations.
  • 655
  • 11 Feb 2022
Topic Review
sPLA2s in Skin Homeostasis and Disease
Phospholipase A2 (PLA2) enzymes hydrolyze the sn-2 position of glycerophospholipids (hereafter phospholipids) to generate free fatty acids (FFAs) and lysophospholipids (LPLs). In contrast to intracellular PLA2s, secreted PLA2s (sPLA2) are ideally positioned to cleave phospholipids available on the cell surface or in the extracellular milieu. The sPLA2 family in mammals contains 11 members, namely IB, IIA, IIC (present in mice and rats, but pseudogene in humans), IID, IIE, IIF, III, V, X, XIIA, and XIIB (catalytically inactive), according to their sequence homology as well as the number and position of disulfide bonds.
  • 655
  • 27 Apr 2023
Topic Review
Role of ADAMTS Proteoglycanases in Aortic Disease
Thoracic aortic aneurysm and dissection (TAAD) are complex disease states with high morbidity and mortality that pose significant challenges to early diagnosis. The extracellular matrix (ECM) plays a crucial role in regulating the aortic structure and function. The histopathologic hallmark termed medial degeneration is characterised by smooth muscle cell (SMC) loss, the degradation of elastic and collagen fibres and proteoglycan (PG) accumulation. Covalently attached to the protein core of PGs are a number of glycosaminoglycan chains, negatively charged molecules that provide flexibility, compressibility, and viscoelasticity to the aorta. PG pooling in the media can produce discontinuities in the aortic wall leading to increased local stress. The accumulation of PGs is likely due to an imbalance between their synthesis by SMCs and decreased proteolysis by A Disintegrin-like and Metalloproteinase with Thrombospondin motifs (ADAMTS) proteoglycanases in the ECM. Mouse models of TAAD indicated that these proteases exert a crucial, albeit complex and not fully elucidated, role in this disease. This has led to a mounting interest in utilising ADAMTS proteoglycanases as biomarkers of TAAD.
  • 655
  • 02 Aug 2023
Topic Review
Cancer Cells and Induced Pluripotent Stem Cells
Cancer cells, especially cancer stem cells (CSCs), share many molecular features with induced pluripotent stem cells (iPSCs) that enable the derivation of induced pluripotent cancer cells by reprogramming malignant cells. Conversely, normal iPSCs can be converted into cancer stem-like cells with the help of tumor microenvironment components and genetic manipulation. These CSC models can be utilized in oncogenic initiation and progression studies, understanding drug resistance, and developing novel therapeutic strategies.
  • 655
  • 25 Jan 2024
Topic Review
Time-Restricted Feeding and Obesity
Obesity is a complex multifactorial disease involving environmental factors, genetic predispositions, and human behaviors. Obesity has been commonly associated with muscle dysfunction and given the important metabolic roles and contribution to physical activity, maintaining muscle health is key to attenuation and prevention. A possible therapeutic strategy involves the implementation of a behavior intervention known as time-restricted feeding (TRF) which has garnered attention from the scientific community due to its associated benefits in metabolism and attenuation of obesity among others.
  • 654
  • 28 Jan 2023
Topic Review
Extracellular Adenosine Triphosphate Sources and Signalling
Myocardial remodelling is a molecular, cellular, and interstitial adaptation of the heart in response to altered environmental demands. The heart undergoes reversible physiological remodelling in response to changes in mechanical loading or irreversible pathological remodelling induced by neurohumoral factors and chronic stress, leading to heart failure. Adenosine triphosphate (ATP) is one of the potent mediators in cardiovascular signalling that act on the ligand-gated (P2X) and G-protein-coupled (P2Y) purinoceptors via the autocrine or paracrine manners. These activations mediate numerous intracellular communications by modulating the production of other messengers, including calcium, growth factors, cytokines, and nitric oxide. ATP is known to play a pleiotropic role in cardiovascular pathophysiology, making it a reliable biomarker for cardiac protection.
  • 654
  • 08 Mar 2023
Topic Review
Effect of H. sabdariffa Extract on Obesity
H. sabdariffa derived bioactive compounds are potent in the treatment of obesity with an evident reduction in body weight, inhibition of lipid accumulation and suppression of adipogenesis through the PPARγ pathway and other transcriptional factors. 
  • 653
  • 30 Nov 2021
Topic Review
Effort Distribution in Heavy Glycolytic Trials
Short, intensive, but above lactate threshold physical trials or competitions which last <1 min but are close to this time limit, are on the border between glycolytic and aerobic efforts. The distribution of effort is critical in these tasks to achieve the best possible results. There are several approaches, grounded in the philosophical basis of effort, which determine effort distribution. The problem is still open and a clear direction has not yet emerged from the available studies on the topic. 
  • 653
  • 29 Mar 2022
Topic Review
Alternative Electron Sources for Cytochrome P450s Catalytic Cycle
The functional significance of cytochrome P450s (CYP) enzymes is their ability to catalyze the biotransformation of xenobiotics and endogenous compounds. P450 enzymes catalyze regio- and stereoselective oxidations of C-C and C-H bonds in the presence of oxygen as a cosubstrate. Initiation of cytochrome P450 catalytic cycle needs an electron donor (NADPH, NADH cofactor) in nature or alternative artificial electron donors such as electrodes, peroxides, photo reduction, and construction of enzymatic “galvanic couple”.
  • 653
  • 25 Jun 2023
Topic Review
E2F-RB-p53 Pathway in Tumor Suppression
The transcription factor E2F links the RB pathway to the p53 pathway upon loss of function of pRB, thereby playing a pivotal role in the suppression of tumorigenesis. E2F fulfills a major role in cell proliferation by controlling a variety of growth-associated genes. The activity of E2F is controlled by the tumor suppressor pRB, which binds to E2F and actively suppresses target gene expression, thereby restraining cell proliferation. Signaling pathways originating from growth stimulative and growth suppressive signals converge on pRB (the RB pathway) to regulate E2F activity. In most cancers, the function of pRB is compromised by oncogenic mutations, and E2F activity is enhanced, thereby facilitating cell proliferation to promote tumorigenesis. Upon such events, E2F activates the Arf tumor suppressor gene, leading to activation of the tumor suppressor p53 to protect cells from tumorigenesis. ARF inactivates MDM2, which facilitates degradation of p53 through proteasome by ubiquitination (the p53 pathway). P53 suppresses tumorigenesis by inducing cellular senescence or apoptosis. Hence, in almost all cancers, the p53 pathway is also disabled. 
  • 653
  • 03 Jan 2024
Topic Review
Noncoding RNAs of Extracellular Vesicles in Tumor Angiogenesis
Extracellular vesicles (EVs) act as multifunctional regulators of intercellular communication and are involved in diverse tumor phenotypes, including tumor angiogenesis, which is a highly regulated multi-step process for the formation of new blood vessels that contribute to tumor proliferation. EVs induce malignant transformation of distinct cells by transferring DNAs, proteins, lipids, and RNAs, including noncoding RNAs (ncRNAs). However, the functional relevance of EV-derived ncRNAs in tumor angiogenesis remains to be elucidated. 
  • 652
  • 11 Apr 2022
Topic Review
Capturing Transitional Pluripotency through Proline Metabolism
An imbalance in proline metabolism shifts mouse ESCs toward a stable naïve-to-primed intermediate state of pluripotency. Proline-induced cells (PiCs), also named primitive ectoderm-like cells (EPLs), are phenotypically metastable, a trait linked to a rapid and reversible relocalization of E-cadherin from the plasma membrane to intracellular membrane compartments. The ESC-to-PiC transition relies on the activation of Erk and Tgfβ/Activin signaling pathways and is associated with extensive remodeling of the transcriptome, metabolome and epigenome. PiCs maintain several properties of naïve pluripotency (teratoma formation, blastocyst colonization and 3D gastruloid development) and acquire a few traits of primed cells (flat-shaped colony morphology, aerobic glycolysis metabolism and competence for primordial germ cell fate). 
  • 652
  • 15 Aug 2022
Topic Review
Mechanobiology of Metastasis
The major cause (more than 90%) of all cancer-related deaths is metastasis, thus its prediction can critically affect the survival rate. Metastases are predicted by lymph-node status, tumor size, histopathology and genetic testing. The identification of new potential prognostic factors will be an important source of risk information for the practicing oncologist, potentially leading to enhanced patient care through the proactive optimization of treatment strategies. Mechanobiology, as a branch of biomechanics and/or a branch of biology, has reached a mature stage mainly because of the significant technological and methodological advances at the cellular, subcellular, and molecular levels and the need to disclose the mechanical basis of biology. The application of mechanobiology to medicine (mechanomedicine) may help advance human health and improve diagnostics, treatment, and therapeutics of cancer.
  • 652
  • 23 Mar 2023
Topic Review
Salivary Amino Acid Levels in Cancer
Amino acids, as a raw material for protein synthesis and a product of protein metabolism, enter the body or are synthesized endogenously. They play mainly physiological roles as major metabolites and regulators of metabolism among the most important compounds.
  • 652
  • 24 Aug 2023
Topic Review
Liquid Biopsy-Derived Exosomal MicroRNAs
Circulatory tumor-derived exosomal microRNAs (miRNAs) play key roles in cancer development/progression. We aimed to assess the diagnostic/prognostic value of circulating exosomal miRNA in thyroid cancer (TC). A search in PubMed, Scopus, Web of Science, and Science Direct up to 22 May 2021 was performed. The true/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain the pooled sensitivity, specificity, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95%CIs). The meta-analysis included 12 articles consisting of 1164 Asian patients and 540 controls. All miRNAs were quantified using qRT-PCR assays. The pooled sensitivity was 82% (95%CI = 77–86%), pooled specificity was 76% (95%CI = 71–80%), and pooled DOR was 13.6 (95%CI = 8.8–21.8). The best biomarkers with high sensitivity were miR-16-2-3p (94%), miR-223-5p (91%), miR-130a-3p (90%), and miR182-5p (94%). Similarly, they showed high specificity, in addition to miR-34c-5p. Six panels of two to four exosomal miRNAs showed higher diagnostic values with an area under the curve (AUC) ranging from 0.906 to 0.981. The best discriminative ability to differentiate between cancer and non-cancer individuals was observed for miR-146b-5p + miR-223-5p + miR-182-5p (AUC = 0.981, sensitivity = 93.8% (84.9–98.3), specificity = 92.9% (76.5–99.1)). In conclusion, the expression levels of exosomal miRNAs could predict TC. 
  • 651
  • 11 Oct 2021
Topic Review
MiRNAs in Adrenocortical Carcinoma
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis and a high rate of recurrence and mortality. Therapeutic options are limited. In some cases, the distinction of ACCs from benign adrenal neoplasms with the existing widely available pathological and histopathological tools is difficult. Thus, new biomarkers have been tested. More than 10 miRNAs validated by multiple studies were found to present a diagnostic and prognostic role for ACC patients, from which miR-483-5p and miR-195 were the most frequently met biomarkers. In particular, upregulation of miR-483-5p and downregulation of miR-195 were the most commonly validated molecular alterations. Unfortunately, data on the therapeutic role of miRNA are still scarce and limited mainly at the experimental level. Thus, the role of miRNA regulation in ACC remains an area of active research.
  • 651
  • 22 Nov 2021
Topic Review
Long Non-Coding RNAs in Ewing Sarcoma Pathogenesis
Ewing sarcoma (ES) is a rare aggressive cancer of bone and soft tissue that is mainly characterized by a reciprocal chromosomal translocation. As a result, about 90% of cases express the EWS-FLI1 fusion protein that has been shown to function as an aberrant transcription factor driving sarcomagenesis. ES is the second most common malignant bone tumor in children and young adults. Current treatment modalities include dose-intensified chemo- and radiotherapy, as well as surgery. Despite these strategies, patients who present with metastasis or relapse still have dismal prognosis, warranting a better understanding of treatment resistant-disease biology in order to generate better prognostic and therapeutic tools.
  • 651
  • 20 Apr 2022
Topic Review
Optimization of Genome Knock-In Method for Plants
Plant expression systems are currently regarded as promising alternative platforms for the production of recombinant proteins, including the proteins for biopharmaceutical purposes. However, the accumulation level of a target protein in plant expression systems is still rather low compared with the other existing systems, namely, mammalian, yeast, and E. coli cells. To solve this problem, numerous methods and approaches have been designed and developed. At the same time, the random nature of the distribution of transgenes over the genome can lead to gene silencing, variability in the accumulation of recombinant protein, and also to various insertional mutations. The current research considered inserting target genes into pre-selected regions of the plant genome (genomic “safe harbors”) using the CRISPR/Cas system. Regions of genes expressed constitutively and at a high transcriptional level in plant cells (housekeeping genes) that are of interest as attractive targets for the delivery of target genes were characterized.
  • 650
  • 05 May 2022
Topic Review
O3 Effect on Kidney Damage
Ozone (O3) is a reactive oxygen species (ROS) that can interact with cellular components and cause oxidative stress. Following said logic, if O3 induces such a stressful milieu, how does it exert antioxidant functions? This is mediated by controlled toxicity produced by low concentrations of O3, which enhance the cell’s suppliance of antioxidant properties without causing any further damage. O3 therapy has been shown to be effective when applied before or after traumatic renal procedures, whether caused by ischemia, xenobiotics, chronic damage, or other models.
  • 650
  • 22 Mar 2023
Topic Review
Differentially Regulated miRNAs in Breast Cancer Progression
Breast cancer is a complex and enigmatic disease caused by a series of alterations in genes that control cell growth and proliferation. miRNA was discovered by Ambros and co-workers in Caenorhabditis elegans (Nematode), during their genetic study to investigate defects in the temporal control of C. elegans development.
  • 650
  • 01 Apr 2024
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