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Topic Review
Protein Misfolding and Aggregation in Proteinopathies
Proteins are central to life functions. Alterations in the structure of proteins are reflected in their function. Misfolded proteins and their aggregates present a significant risk to the cell. Cells have a diverse but integrated network of protection mechanisms. Streams of misfolded proteins that cells are continuously exposed to must be continually monitored by an elaborated network of molecular chaperones and protein degradation factors to control and contain protein misfolding problems. Aggregation inhibition properties of small molecules such as polyphenols are important as they possess other beneficial properties such as antioxidative, anti-inflammatory, and pro-autophagic properties and help neuroprotection.
  • 605
  • 15 Feb 2023
Topic Review
Fractalkine/CX3CR1 in Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is a cardiac condition with structural and functional impairment, where either the left ventricle or both ventricular chambers are enlarged, coinciding with reduced systolic pump function (reduced ejection fraction, rEF). The prevalence of DCM is more than 1:250 individuals, and mortality largely due to heart failure in two-third of cases, and sudden cardiac death in one-third of patients. Damage to the myocardium, whether from a genetic or environmental cause such as viruses, triggers inflammation and recruits immune cells to the heart to repair the myocardium. Examination of myocardial biopsy tissue often reveals an inflammatory cell infiltrate, T lymphocyte (T cell) infiltration, or other activated immune cells. Despite medical therapy, adverse outcomes for DCM remain. The evidence base and existing literature suggest that upregulation of CX3CR1, migration of immune cells, together with cytomegalovirus (CMV) seropositivity is associated with worse outcomes in patients with dilated cardiomyopathy.
  • 605
  • 16 Oct 2023
Topic Review
Monomeric Extracellular Ubiquitin
Ubiquitin (Ub) was discovered in 1975 in bovine thymus and subsequently found in multiple organisms and tissues. Ub is a small 76-amino-acid protein with a molecular weight of 8.6 kDa and a surface area of 4800 Å2. It is highly conserved across species. Indeed, human and mouse Ub are identical and differ from yeast by only two amino acids (96% sequence identity), indicating a well-conserved role in regulating important cellular processes across diverse and evolutionarily distant organisms. Ub is encoded by four different genes in humans; two of them, UBA52 and RSP27A, encode for a single Ub fused to the ribosomal L40 and S27A proteins, respectively, whereas the other two, UBB and UBC, produce three and nine head-to-tail tandem Ubs with a C-terminal cysteine (C) or valine (V), respectively. After expression, the polyubiquitins, as well as the C-terminal C or V extensions, are processed by specific cellular deubiquitinases (DUBs) to generate Ub.
  • 605
  • 18 Feb 2024
Topic Review
Biomarkers in Peripheral Arterial Disease
Peripheral arterial disease (PAD) of the lower extremities is a chronic illness predominantly of atherosclerotic aetiology, associated to traditional cardiovascular (CV) risk factors. It is one of the most prevalent CV conditions worldwide in subjects >65 years, estimated to increase greatly with the aging of the population, becoming a severe socioeconomic problem in the future. The narrowing and thrombotic occlusion of the lower limb arteries impairs the walking function as the disease progresses, increasing the risk of CV events (myocardial infarction and stroke), amputation and death. Despite its poor prognosis, PAD patients are scarcely identified until the disease is advanced, highlighting the need for reliable biomarkers for PAD patient stratification, that might also contribute to define more personalized medical treatments. 
  • 604
  • 26 Apr 2021
Topic Review
Human Pathogens Hijacking the Ubiquitin–Proteasome System
Ubiquitin, a small protein, is well known for tagging target proteins through a cascade of enzymatic reactions that lead to protein degradation. The ubiquitin tag, apart from its signaling role, is paramount in destabilizing the modified protein.
  • 602
  • 14 Dec 2023
Topic Review
Carbonic Anhydrase in Carbon Capture Storage
Direct biocatalytic processes for CO2 capture and transformation in value-added chemicals may be considered a useful tool for reducing the concentration of this greenhouse gas in the atmosphere. Among the other enzymes, carbonic anhydrase (CA) and formate dehydrogenase (FDH) are two key biocatalysts suitable for this challenge, facilitating the uptake of carbon dioxide from the atmosphere in complementary ways. 
  • 601
  • 25 Jul 2023
Topic Review
Purification of Myosin from Bovine Tracheal Smooth Muscle
Dynamic regulation of myosin filaments is a crucial factor in the ability of airway smooth muscle (ASM) to adapt to a wide length range. Increased stability or robustness of myosin filaments may play a role in the pathophysiology of asthmatic airways. Biochemical techniques for the purification of myosin and associated regulatory proteins could help elucidate potential alterations in myosin filament properties of asthmatic ASM. 
  • 600
  • 09 May 2023
Topic Review
LOXL2 in Hepatocellular Carcinoma
LOXL2, a copper-dependent amine oxidase, has emerged as a promising therapeutic target in hepatocellular carcinoma (HCC). Increased LOXL2 expression in HCC has been linked with an aggressive phenotype and represents a poor prognostic factor.
  • 599
  • 02 Aug 2023
Topic Review
Homeobox Genes in Bladder Cancer
Homeobox genes serve as master regulatory transcription factors that regulate gene expression during embryogenesis. A homeobox gene may have either tumor-promoting or tumor-suppressive properties depending on the specific organ or cell lineage where it is expressed. The dysregulation of homeobox genes has been reported in various human cancers, including bladder cancer.
  • 598
  • 24 Aug 2023
Topic Review
Resveratrol and Quercetin in Reperfusion Injury
Ischemia-reperfusion myocardial damage is a paradoxical tissue injury occurring during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. Although this damage could account for up to 50% of the final infarct size, there has been no available pharmacological treatment until now. Oxidative stress contributes to the underlying production mechanism, exerting the most marked injury during the early onset of reperfusion. So far, antioxidants have been shown to protect the AMI patients undergoing PCI to mitigate these detrimental effects; however, no clinical trials to date have shown any significant infarct size reduction. Myocardial ischemia/reperfusion damage results from diverse oxidative stress producing mechanisms. 
  • 597
  • 27 Jun 2022
Topic Review
Kinases on Double Duty
Phosphorylation facilitates the regulation of all fundamental biological processes, which has triggered extensive research of protein kinases and their roles in human health and disease. In addition to their phosphotransferase activity, certain kinases have evolved to adopt additional catalytic functions, while others have completely lost all catalytic activity.
  • 597
  • 26 May 2022
Topic Review
MicroRNAs as Potential Clinical Biomarkers for Ovarian Cancer
Ovarian cancer is a commonly diagnosed malignancy in women. When diagnosed at an early stage, survival outcomes are favourable for the vast majority, with up to 90% of ovarian cancer patients being free of disease at 5 years follow-up. Unfortunately, ovarian cancer is typically diagnosed at an advanced stage due to the majority of patients remaining asymptomatic until the cancer has metastasised, resulting in poor outcomes for the majority. While the molecular era has facilitated the subclassification of the disease into distinct clinical subtypes, ovarian cancer remains managed and treated as a single disease entity. Biomarkers are objectively measured such that they are informative of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention. The incorporation of biomarkers into clinical practice can improve early detection of disease and aid the design of treatment regimens specific for individual patients. However, clinically established biomarkers for ovarian cancer lack robust reliability and specificity. MicroRNAs (miRNAs) are small (19–25 nucleotides), endogenous molecules which are integral to regulating gene expression. Aberrant miRNA expression profiles have been described in several cancers, and have been implicated to be useful biomarkers which may aid cancer diagnostics and treatment.
  • 597
  • 29 Jan 2023
Topic Review
Flavonoids in Chemoprevention and Chemotherapy
Flavonoids have demonstrated antioxidant, antiviral, anticancer, and anti-inflammatory effects. Flavonoid type, bioavailability, and possible method of action determine these biological actions. These low-cost pharmaceutical components have significant biological activities and are beneficial for several chronic disorders, including cancer. 
  • 597
  • 11 Apr 2023
Topic Review
Pathogen-Induced Epigenetic Modifications in Cancer in Africa
Cancer remains a global burden with multiple causality. Over the years, studies have linked various infectious pathogens with various cancer. Nonetheless, precise mechanism(s) by which pathogens induce or enhance cancer development remains largely obscure. Since cancers are almost invariably associated with genetic alterations, pathogen-induced cancers are likely to be linked with genetic alterations, including epigenetic modification, a change in gene expression without changes in the DNA sequences. Indeed, studies have reported associations between some infectious pathogens can induce epigenetic changes. This implies that pathogens could be involved in cancer development through the modification of host epigenetic factors. With the high burden of infectious pathogens, Africa is at a higher risk of pathogen-mediated cancers. To tame a potential rise of such cancers, there is the need for thorough understanding of the role of tropical infectious pathogens in regulating epigenetic modifications that could be associated with cancer development.
  • 596
  • 20 Dec 2021
Topic Review
Osteoarthritis Etiopathogenesis
Osteoarthritis (OA) is acknowledged as a major degenerative and progressive joint disease responsible for significant pain and disability in the adult population. The incidence of OA across the globe has risen significantly in the last few decades due to metabolic syndrome and aging. This disease can often be challenging to treat as it presents a multifactorial nature, being mainly characterized by the physiological and architectural changes in the joint compartment as a whole.
  • 596
  • 17 Jul 2023
Topic Review
SMIFH2 Targets
The discovery of small molecule inhibitor of formin homology 2 domains (SMIFH2) has provided a unique tool to explore formins’ functions from the molecular to the organismal scales. Due to the important pathophysiological roles of formins in eukaryotes, SMIFH2 has been widely used.
  • 595
  • 02 Jun 2023
Topic Review
Sphingolipids and Lymphomas
Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. 
  • 594
  • 26 May 2022
Topic Review
Glycosphingolipids Abundance in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Low numbers of HCC patients being suitable for liver resection or transplantation and multidrug resistance development during pharmacotherapy leads to high death rates for HCC patients. Understanding the molecular mechanisms of HCC etiology may contribute to the development of novel therapeutic strategies for prevention and treatment of HCC. UDP-glucose ceramide glycosyltransferase (UGCG), a key enzyme in glycosphingolipid metabolism, generates glucosylceramide (GlcCer), which is the precursor for all glycosphingolipids (GSLs). Since UGCG gene expression is altered in 0.8% of HCC tumors, GSLs may play a role in cellular processes in liver cancer cells.
  • 593
  • 11 May 2022
Topic Review
BRCA1 and Metastasis: Outcome of Defective DNA Repair
BRCA1 has critical functions in accurately repairing double stand breaks in the DNA through a process known as homologous recombination. BRCA1 also has various functions in other cellular processes that safeguard the genome. Thus, mutations or silencing of this tumor suppressor significantly increases the risk of developing breast, ovarian, and other cancers. The objective of this review is to provide significant insights into the mechanisms by which BRCA1 mutations contribute to the metastatic and aggressive nature of the tumor cells. 
  • 592
  • 07 Jan 2022
Topic Review
Oxidative Stress and Bio-Regulation
Reactive oxygen species (ROS) and free radicals work to maintain homeostasis in the body, but their excessive production causes damage to the organism. The human body is composed of a variety of cells totaling over 60 trillion cells. Each cell performs different functions and has a unique lifespan. The lifespan of cells is preprogrammed in their genes, and the death of cells that have reached the end of their lifespan is called apoptosis. This is contrary to necrosis, which is the premature death of cells brought about by physical or scientific forces. Each species has its own unique lifespan, which in humans is estimated to be up to 120 years. Elucidating the mechanism of the death of a single cell will lead to a better understanding of human death, and, conversely, the death of a single cell will lead to exploring the mechanisms of life. In this sense, research on active oxygen and free radicals, which are implicated in biological disorders and homeostasis, requires an understanding of both the physicochemical as well as the biochemical aspects. Based on the discussion above, it is clear to see that active oxygen and free radicals have dual functions of both injuring and facilitating homeostasis in living organisms.
  • 592
  • 27 Mar 2024
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