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Topic Review
Keap1-Nrf2 Heterodimer in Sickle Cell Disease
Sickle cell disease (SCD) is a monogenic inheritable disease characterized by severe anemia, increased hemolysis, and recurrent, painful vaso-occlusive crises due to the polymerization of hemoglobin S (HbS)-generated oxidative stress. Only four drugs are approved for SCD in the US. However, each of these drugs affects only a limited array of SCD pathologies. Importantly, curative therapies, such as gene therapy, or hematopoietic stem cell transplantation are not available for every patient because of their high costs, availability of donor matching, and their serious adverse effects. Therefore, there is an unmet medical need for novel therapeutic strategies that target broader SCD sequelae. SCD phenotypic severity can be alleviated by increasing fetal hemoglobin (HbF) expression. This results in the inhibition of HbS polymerization and thus sickling, and a reduction in oxidative stress. The efficacy of HbF is due to its ability to dilute HbS levels below the threshold required for polymerization and to influence HbS polymer stability in RBCs. Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1)-complex signaling is one of the most important cytoprotective signaling controlling oxidative stress. Nrf2 is present in most organs and, after dissociation from Keap1, it accumulates in the cytoplasm, then translocates to the nucleus where it binds to the antioxidant response element (ARE) sequences and increases the expression of various cytoprotective antioxidant genes. Keeping this in mind, various researchers have proposed a role of multiple agents, more importantly tert-Butylhydroquinone (tBHQ), curcumin, etc., (having electrophilic properties) in inhibiting keap1 activity, so that Nrf2 can translocate to the nucleus to activate the gamma globin gene, thus maintaining alpha-hemoglobin-stabilizing protein (AHSP) and HbF levels. This leads to reduced oxidative stress, consequently minimizing SCD-associated complications. 
  • 595
  • 29 Mar 2023
Topic Review
Relevance of Genetic Identification in Natural Catastrophes
Different types of catastrophes, including from natural causes, armed conflicts and different acts of terrorism, lead not only to movement and disappearance but also to the death of civilians, demanding a prompt and effective response concerning the identification and delivery of individuals to their families.
  • 595
  • 14 Jul 2023
Topic Review
Metagenomics in Biofouling Research
Biofouling is the growth of organisms on wet surfaces. Biofouling includes micro- (bacteria and unicellular algae) and macrofouling (mussels, barnacles, tube worms, bryozoans, etc.) and is a major problem for industries. However, the settlement and growth of some biofouling species, like oysters and corals, can be desirable. Thus, it is important to understand the process of biofouling in detail. Modern “omic” techniques, such as metabolomics, metagenomics, transcriptomics, and proteomics, provide unique opportunities to study biofouling organisms and communities and investigate their metabolites and environmental interactions.  Because "omics" originate from biomedical research and especially work at the cellular level, the learning curve for work in the environment is steep.  Researchers envision that as use of "omics" techniques especially combining different "omics" to address complex issues like biofouling will be transformational.
  • 594
  • 03 Jul 2023
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
Topic Review
Side-Chain Functional Groups in Bacterial Glycans
Glycans on the surface of bacteria have diverse and essential biological functions and have widely been employed for treating various bacterial infectious diseases. Furthermore, these glycans comprise various functional groups, such as O-, N-, and carboxyl-modified, which significantly increase the diversity of glycan structures. These functional groups are not only crucial for glycans’ structural identity but are also essential for their biological functions. Therefore, a clear understanding of the biological functions of these modified groups in corresponding bacterial glycans is crucial for their medical applications. 
  • 590
  • 26 Oct 2023
Topic Review
Cerebellum in Neurodegenerative Disorders
An important part of the central nervous system (CNS), the cerebellum is involved in motor control, learning, reflex adaptation, and cognition. Diminished cerebellar function results in the motor and cognitive impairment observed in patients with neurodegenerative disorders such as Alzheimer’s disease (AD), vascular dementia (VD), Parkinson’s disease (PD), Huntington’s disease (HD), spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Friedreich’s ataxia (FRDA), and multiple sclerosis (MS), and even during the normal aging process. In most neurodegenerative disorders, impairment mainly occurs as a result of morphological changes over time, although during the early stages of some disorders such as AD, the cerebellum also serves a compensatory function. Biological aging is accompanied by changes in cerebellar circuits, which are predominantly involved in motor control.
  • 590
  • 31 Jan 2024
Topic Review
Mitochondrial Phenotype in Obesity and Insulin Resistance
African Americans (AA) are disproportionately burdened by metabolic diseases. While largely unexplored between Caucasian (C) and AA, differences in mitochondrial bioenergetics may provide crucial insight to mechanisms for increased susceptibility to metabolic diseases. AA display lower total energy expenditure and resting metabolic rate compared to C, but paradoxically have a higher amount of skeletal muscle mass, suggestive of inherent energetic efficiency differences between these races.
  • 584
  • 01 Jul 2022
Topic Review
Pathogenesis of FGF23-Related Hypophosphatemic Diseases
Since phosphate is indispensable for skeletal mineralization, chronic hypophosphatemia causes rickets and osteomalacia. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes in bone, functions as the central regulator of phosphate metabolism by increasing the renal excretion of phosphate and suppressing the production of 1,25-dihydroxyvitamin D. The excessive action of FGF23 results in hypophosphatemic diseases, which include a number of genetic disorders such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). Phosphate-regulating gene homologous to endopeptidase on the X chromosome (PHEX), dentin matrix protein 1 (DMP1), ectonucleotide pyrophosphatase phosphodiesterase-1, and family with sequence similarity 20c, the inactivating variants of which are responsible for FGF23-related hereditary rickets/osteomalacia, are highly expressed in osteocytes, similar to FGF23, suggesting that they are local negative regulators of FGF23. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by cleavage-resistant variants of FGF23, and iron deficiency increases serum levels of FGF23 and the manifestation of symptoms in ADHR. Enhanced FGF receptor (FGFR) signaling in osteocytes is suggested to be involved in the overproduction of FGF23 in XLH and autosomal recessive hypophosphatemic rickets type 1, which are caused by the inactivation of PHEX and DMP1, respectively. TIO is caused by the overproduction of FGF23 by phosphaturic tumors, which are often positive for FGFR. FGF23-related hypophosphatemia may also be associated with McCune-Albright syndrome, linear sebaceous nevus syndrome, and the intravenous administration of iron. 
  • 583
  • 09 Aug 2022
Topic Review
Botulinum Neurotoxins beyond Neurons
Numerous studies have highlighted the significant use of botulinum neurotoxins (BoNTs) in the human therapy of various motor and autonomic disorders. The therapeutic action is exerted with the selective cleavage of specific sites of the SNARE’s protein complex, which plays a key role in the vesicular neuroexocytosis which is responsible for neural transmission. The primary target of the BoNTs’ action is the peripheral neuromuscular junction (NMJ), where, by blocking cholinergic neurons releasing acetylcholine (ACh), they interfere with neural transmission. A great deal of experimental evidence has demonstrated that BoNTs are also effective in blocking the release of other neurotransmitters or neuromodulators, such as glutamate, substance-P, and CGRP, and they can interfere with the function of glial cells, both at the peripheral and central level.
  • 583
  • 31 Oct 2022
Topic Review
Antimicrobial Peptides Demonstrate Activity against Resistant Bacterial Pathogens
The antimicrobial resistance crisis is an ongoing major threat to public health safety. Low- and middle-income countries are particularly susceptible to higher fatality rates and the economic impact of antimicrobial resistance (AMR). As an increasing number of pathogens emerge with multi- and pan-drug resistance to last-resort antibiotics, there is an urgent need to provide alternative antibacterial options to mitigate disease transmission, morbidity, and mortality. As identified by the World Health Organization (WHO), critically important pathogens such as Klebsiella and Pseudomonas species are becoming resistant to last-resort antibiotics including colistin while being frequently isolated from clinical cases of infection. Antimicrobial peptides are potent amino acid sequences produced by many life forms from prokaryotic, fungal, plant, to animal species. These peptides have many advantages, including their multi-hit mode of action, potency, and rapid onset of action with low levels of resistance being evident. These innate defense mechanisms also have an immune-stimulating action among other activities in vivo, thus making them ideal therapeutic options. Large-scale production and formulation issues (pharmacokinetics, pharmacodynamics), high cost, and protease instability hinder their mass production and limit their clinical application.
  • 583
  • 23 Aug 2023
Topic Review
Potassium Binders for Optimizing Therapies in Heart Failure
Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K+ and to promote correct upgrades of therapies.
  • 582
  • 16 Aug 2022
Topic Review
Apoptosis in Brief
Apoptosis, or programmed cell death, is a vital biological process crucial for tissue balance, embryonic development, and removing damaged cells. Discovered in the 1970s, it has been extensively researched, revealing intricate molecular pathways. This research explores apoptosis comprehensively, focusing on its roles in tissue maintenance, embryogenesis, and disease. It delves into molecular mechanisms, regulatory proteins, and implications for conditions like cancer and neurodegenerative disorders. Additionally, it highlights apoptosis's pivotal role in immunology, shaping the adaptive immune response. Understanding apoptosis offers valuable insights into various fields of biology and medicine, promising therapeutic advancements and deeper comprehension of life's intricacies.
  • 582
  • 13 Sep 2023
Topic Review
Molecular Diagnostic Tools against SARS-CoV-2 in Poland
The most effective way to stop the spread of COVID-19 (coronavirus disease 2019) is to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and isolate those infected as soon as possible. More than 1000 types of molecular and antigen-based immunoassay tests to detect SARS-CoV-2 are commercially available worldwide.
  • 579
  • 03 Jan 2023
Topic Review
Monocytes in Tumorigenesis and Tumor Immunotherapy
Monocytes are highly plastic innate immune cells that display significant heterogeneity during homeostasis, inflammation, and tumorigenesis. Tumor-induced systemic and local microenvironmental changes influence the phenotype, differentiation, and distribution of monocytes. Meanwhile, monocytes and their related cell subsets perform an important regulatory role in the development of many cancers by affecting tumor growth or metastasis. Thanks to recent advances in single-cell technologies, the nature of monocyte heterogeneity and subset-specific functions have become increasingly clear, making it possible to systematically analyze subset-specific roles of monocytes in tumorigenesis.
  • 579
  • 03 Jul 2023
Topic Review
Epigenetic Crosstalk within the Microvascular Unit
Epigenetic changes might be classified into three main categories: (i) DNA chemical modifications (e.g., DNA methylation); (ii) histone tails post-translational modifications; (iii) gene expression regulation by noncoding RNAs (e.g., microRNAs (miRNAs), PIWI-interacting RNAs, endogenous short interfering RNAs, long noncoding RNAs). DNA methylation consists of the binding of a methyl group to the 5′ region of a cytosine of the cytosine–guanine dinucleotide (CpG), defined as a CpG island. CpG methylation functionally suppresses gene transcription and is mediated by DNA methyltransferases (DNMTs). In addition to DNA methylation, DNA hydroxymethylation (i.e., the binding of a methyl group to the 5′ cytosine of a CpG island) has recently been discovered to be an epigenetic marker involved in the methylation reprogramming. However, its precise biological meaning still needs further investigation. Histone tails post-translational modifications include methylation, acetylation, ubiquitination and phosphorylation. They come as specific clustered patterns, allowing for the hyperexpression of genes by opening the chromatin, or vice versa. The main enzymes regulating these processes are histone acetyltransferases, deacetylases, methyltransferases and demethylases. While acetylation is, overall, a chromatin opening modification, the effect of methylation depends on the methylated residue and the number of methylations. Finally, noncoding RNAs are involved in transcriptional and post-transcriptional regulations. In particular, based on their size, they can be further classified into small noncoding RNA (<200 nucleotides), including miRNAs, PIWI-interacting RNAs and endogenous short interfering RNAs, and long noncoding RNAs (200–2000 nucleotides). Their potential pathogenetic role might indicate their targeting as a promising therapeutic strategy.
  • 578
  • 15 Mar 2023
Topic Review
Lipid Peroxidation Assays
This research comprehensively explores the techniques for evaluating lipid peroxidation, a critical process in oxidative stress implicated in various diseases. Direct methods, including TBARS assay, HPLC-based analyses, GC-MS, EPR spectroscopy, and mass spectrometry imaging, offer precise quantification of lipid peroxidation products. Indirect methods, such as LOOH assays, conjugated dienes assays, F2-isoprostane assays, antioxidant capacity assays, and EMSA, provide insights into downstream effects and antioxidant responses. Balancing specificity and accessibility, these methods collectively advance our understanding of lipid peroxidation's role in health and disease. Integrating these techniques with emerging technologies promises to drive further innovation and therapeutic discoveries in oxidative stress-related conditions.
  • 576
  • 11 Sep 2023
Topic Review
Mitochondrial Neurodegenerative Diseases
Neurodegenerative diseases are characterized by the progressive degeneration of nerve cells. Some neurodegenerative diseases such as Alzheimer’s and Parkinson’s are caused by disorders in the mitochondria, which are organelles present in the eukaryotic cells of animals, plants and fungi, and their function is to produce energy.
  • 575
  • 19 Jul 2023
Topic Review
Ethnomedical Uses of Corymbia Species
Plants have been vital to human survival for aeons, especially for their unique medicinal properties. Trees of the Eucalyptus genus are well known for their medicinal properties. The Corymbia genus comprises bloodwood, spotted and ghost gum trees, which were previously classified as subspecies of the Eucalyptus genus. In 1995, however, DNA and morphological research concluded that bloodwood, spotted and ghost gum trees were genetically distinct from other Eucalyptus species, and they were, therefore, reclassified as members of the Corymbia genus of the Myrtaceae family
  • 572
  • 22 Nov 2023
Topic Review
Circular RNAs Modulate Cancer Hallmark and Molecular Pathways
Circular RNAs (circRNAs) are noncoding products of backsplicing of pre-mRNAs which have been established to possess potent biological functions. Due to their circular nature, the are characterized by high stability. Dysregulated circRNA expression has been linked to diseases including different types of cancer.
  • 569
  • 10 Mar 2022
Topic Review
Animal Models of Rheumatoid Arthritis
Rheumatoid arthritis (RA), a global health concern affecting millions, has prompted extensive research using animal models to develop effective treatments. Among these models, Adjuvant-Induced Arthritis (AIA) and Pristane-Induced Arthritis (PIA) have gained prominence. In part 2 of this series, the unique features, advantages, and limitations of AIA and PIA  were described. These models provide valuable insights into RA but also have specific constraints. By understanding their characteristics and drawbacks, their crucial role in advancing RA research and facilitating the discovery of novel therapies for this debilitating autoimmune disorder were emphasizes, which continues to challenge healthcare worldwide.
  • 569
  • 08 Sep 2023
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