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Topic Review
Circulating Tumor Cells as Precursors of Metastasis
Circulating tumor cells are cancer cells that detach from the primary tumor and enter the bloodstream. These cancer cells in the blood stream eventually result in secondary tumor growth referred to as metastasis. Research on circulating tumor cells is crucial because they can provide valuable insights into cancer progression and treatment response that enhances the patient outcomes. Findings from circulating-tumor-cell-based research can also shed light on cancer metastasis, drug resistance, and tumor evolution, ultimately benefiting the research community by advancing our understanding of cancer biology and guiding the development of innovative treatments. 
  • 642
  • 01 Mar 2024
Topic Review
Interplay of BDNF and Glucocorticoids in Alzheimer’s Disease
Both the brain-derived neurotrophic factor (BDNF) and glucocorticoids (GCs) play multiple roles in various aspects of neurons, including cell survival and synaptic function. BDNF and its receptor TrkB are extensively expressed in neurons of the central nervous system (CNS), and the contribution of the BDNF/TrkB system to neuronal function is evident; thus, its downregulation has been considered to be involved in the pathogenesis of Alzheimer’s disease (AD). GCs, stress-related molecules, and glucocorticoid receptors (GRs) are also considered to be associated with AD in addition to mental disorders such as depression. Importantly, a growing body of evidence suggests a close relationship between BDNF/TrkB-mediated signaling and the GCs/GR system in the CNS.
  • 641
  • 06 Feb 2024
Topic Review
Soil Thermophiles and Their Extracellular Enzymes
During this century, a number of reports have described the potential roles of thermophiles in the upper soil layers during high-temperature periods. Soil thermophiles are able to adapt their extracellular enzyme activities to environmental conditions. These enzymes can present optimum activity under high temperatures and reduced water content. Consequently, these microorganisms have been shown to actively process and decompose substances (including pollutants) under extreme conditions (i.e., desiccation and heat) in soils.
  • 639
  • 03 Jul 2023
Topic Review
Physiological and Anti-Tumor Activities of Vitamin C
Vitamin C (L-ascorbic acid, ascorbate, VC) is an essential nutrient for the normal maintenance of cellular functions, such as neural pathways, molecule biosynthesis (e.g., collagen, norepinephrine), immune signaling, chromatin remodeling, and cell division. This versatile nutrient has the potential as an anti-tumor agent. At high doses, it acts as a pro-oxidant, selectively targeting cancer cells. At low doses, it acts as an antioxidant, enhancing anti-tumor immunity. VC's potential lies in its ability to target cancer stem cells (CSCs), the self-renewing cells responsible for tumor recurrence and chemoresistance. Recent studies suggest that VC can selectively target CSCs via epigenetic and metabolic pathways. Understanding how VC exerts anti-tumor activity by targeting CSCs provides a rationale for its use in cancer treatment.
  • 639
  • 05 Dec 2023
Topic Review
Biological Clock in Ageing and Low-Level Chronic Inflammation
Ageing is a multifactorial physiological manifestation that occurs inexorably and gradually in all forms of life. This process is linked to the decay of homeostasis due to the progressive decrease in the reparative and regenerative capacity of tissues and organs, with reduced physiological reserve in response to stress. Ageing is closely related to oxidative damage and involves immunosenescence and tissue impairment or metabolic imbalances that trigger inflammation and inflammasome formation. One of the main ageing-related alterations is the dysregulation of the immune response, which results in chronic low-level, systemic inflammation, termed “inflammaging”. Genetic and epigenetic changes, as well as environmental factors, promote and/or modulate the mechanisms of ageing at the molecular, cellular, organ, and system levels. Most of these mechanisms are characterized by time-dependent patterns of variation driven by the biological clock. 
  • 637
  • 23 Nov 2022
Topic Review
Dysbiosis and Neurological Conditions
The prevalence of neurological conditions which manifest with chronic pain is increasing globally, where the World Health Organisation has now classified chronic pain as a risk factor for death by suicide. While many chronic pain conditions have a definitive underlying aetiology, non-somatic conditions represent difficult-to-diagnose and difficult-to-treat public health issues. The interaction of the immune system and nervous system has become an important area in understanding the occurrence of neuroinflammation, nociception, peripheral and central sensitisation seen in chronic pain.
  • 636
  • 17 Mar 2023
Topic Review
Pb Induces MCP-1 in the Choroid Plexus
Lead (Pb) is an environmental element that has been implicated in the development of dementia and Alzheimer’s disease (AD). Additionally, innate immune activation contributes to AD pathophysiology. However, the mechanisms involved remain poorly understood. The choroid plexus (CP) is not only the site of cerebrospinal fluid (CSF) production, but also an important location for communication between the circulation and the CSF.
  • 635
  • 30 Mar 2022
Topic Review
Short-Chain Fatty Acids Impact Neonatal Regulatory T Cells
T cells are specialised lymphocytes that play a pivotal role in the adaptive immune response and are marked by their surface expression of a T cell receptor (TCR). Conventional T cells are classically divided into one of two major subtypes based on the identity of their TCR co-receptor: CD4+ T cells or T helper (Th) cells play a key role in orchestrating adaptive immune responses via the production of effector cytokines; CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), are critical mediators in the elimination of virally infected or tumour cells, which they achieve through the release of cytotoxic granules that induce apoptotic or lytic death. Over the first weeks of life, the neonatal gastrointestinal tract is rapidly colonised by a diverse range of microbial species that come to form the ‘gut microbiota’. Microbial colonisation of the neonatal gut is a well-established regulator of several physiological processes that contribute to immunological protection in postnatal life, including the development of the intestinal mucosa and adaptive immunity. However, the specific microbiota-derived signals that mediate these processes have not yet been fully characterised. Short-chain fatty acids (SCFAs), end-products of intestinal bacterial metabolism, as one of the key mediators of immune development in early life. Critical to neonatal health is the development of regulatory T (Treg) cells that promote and maintain immunological tolerance against self and innocuous antigens.
  • 634
  • 21 Sep 2022
Topic Review
Behavioral Ecology of European Plethodontid Salamanders
Plethodontid salamanders (family Plethodontidae) are often used as model organisms to better understand different aspects of behavioral adaptation. This contributed to increase the interest from ethologists and evolutionary biologists regarding amphibian behavioral ecology. The recent advancements on the behavioral ecology of European cave salamanders belonging to the genus Speleomantes are presented herein. Several aspects of Speleomantes behavior were investigated, such as trophic strategies and parental care, while others were neglected, in particular, chemical communication at the intraspecfic level. Possible future directions for successful research should integrate field observations and planned experiments to understand those topics still uninvestigated (e.g., chemical communication and behavioral adaptation that facilitate the permanent colonization of subterranean habitats).
  • 631
  • 06 Dec 2023
Topic Review
Applications of Biobanking in Neuro-Urology
Understanding the molecular mechanisms underlying neuro-urological disorders is crucial for the development of targeted therapeutic interventions. Through the establishment of comprehensive biobanks, researchers can collect and store various biological specimens, including urine, blood, tissue, and DNA samples, to study these mechanisms. In the context of neuro-urology, biobanking facilitates the identification of genetic variations, epigenetic modifications, and gene expression patterns associated with neurogenic lower urinary tract dysfunction. These conditions often present as symptoms of neurological diseases such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, spinal cord injury, and many others. Biobanking of tissue specimens from such patients is essential to understand why these diseases cause the respective symptoms and what can be done to alleviate them. 
  • 631
  • 11 Dec 2023
Topic Review
Systems Immunology Approach for Tumor Microenvironment
The tumor microenvironment (TME) is a complex and dynamic system that plays a critical role in cancer development and progression. It consists of a variety of cell types, including cancer cells, immune cells, and stromal cells (fibroblasts and endothelial cells), as well as extracellular matrix components and signaling molecules.
  • 629
  • 08 Aug 2023
Topic Review
Sources and Biological Activity of Cell-Free DNA
The term cell-free DNA (cfDNA) encompasses all kinds of extracellular DNA molecules found in serum or plasma and other body fluids, and includes genomic DNA (gDNA) and mitochondrial DNA (mtDNA), as well as DNA of bacterial or viral origin. Cell-free DNA (cfDNA), freely circulating in the bloodstream, urine, and other fluids (or encapsulated in vesicles) may be derived from both normal and diseased cells. cfDNA is extremely dynamic and responsive, providing sensitive indicators of changes that are not detectable by standard clinical tests. It can be used as a reliable, safe, and objective tool to reflect disease progression and supplement clinical data in a particular patient, and thus, represents a new path in personalized medicine.
  • 628
  • 07 Oct 2023
Topic Review
Intra-Articular Platelet-Rich Plasma Injections in Knee Osteoarthritis
Primary knee osteoarthritis (OA) continues to be a hard-to-control degenerative disease. Intra-articular corticosteroids are typically advised, but only for short-term pain alleviation, given that their benefits last only a few weeks. The efficacy of hyaluronic acid is controversial. When the aforesaid options fail, total knee arthroplasty is generally recommended as an efficacious treatment. However, it is costly and can involve medical and postoperative complications. Therefore, determining alternate safe and effective treatments for knee OA is paramount. Platelet-rich plasma (PRP) has lately been investigated for the treatment of knee OA.
  • 627
  • 28 Feb 2022
Topic Review
Circadian Gas-Responsive Hemeprotein NPAS2
Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix–loop–helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains.
  • 626
  • 30 Oct 2023
Topic Review
Polyamines and Physical Activity in Musculoskeletal Diseases
Autophagy dysregulation is commonplace in the pathogenesis of several invalidating diseases, such as musculoskeletal diseases. Polyamines are emerging as natural autophagy regulators with strong anti-aging effects. Recent studies indicate that spermidine reverses dysfunctional autophagy and stimulates mitophagy in muscles and heart, preventing senescence. Physical exercise, as polyamines, regulates skeletal muscle mass inducing proper autophagy and mitophagy. In addition, the combination of spermidine supplementation and regular physical exercise could have positive effects on reactivating the autophagic process flux, maintaining the skeletal muscle mass, and delaying its senescence. This suggests that exercise and spermidine may share mediators acting on similar pathways in autophagy and related processes involved in muscle maintenance. Therefore, the established geroprotective effect of spermidine supplementation and regular practice of exercise might also be promising to prevent or improve age-related musculoskeletal diseases. 
  • 621
  • 25 Jun 2023
Topic Review
ER+, Node-Positive Breast Cancer
The majority of breast cancers are oestrogen receptor-positive (ER+). In ER+ cancers, oestrogen acts as a disease driver, so these tumours are likely to be susceptible to endocrine therapy (ET). ET works by blocking the hormone’s synthesis or effect. A significant number of patients diagnosed with breast cancer will have the spread of tumour cells into regional lymph nodes either at the time of diagnosis, or as a recurrence some years later. Patients with node-positive disease have a poorer prognosis and can respond less well to ET. The nodal metastases may be genomically similar or, as is becoming more evident, may differ from the primary tumour. However, nodal metastatic disease is often not assessed, and treatment decisions are almost always based on biomarkers evaluated in the primary tumour. 
  • 619
  • 17 Oct 2023
Topic Review
Neuroprotective Effect of Clobenpropit
Neuroinflammation is defined as one of the key contributors involved in several CNS-related disorders including neurodegenerative diseases. According to experimental evidence, the inflammatory process in the neuron has been shown to cause cell death and neurodegeneration in Parkinson’s (PD), Alzheimer’s (AD), and other neurodegenerative diseases. 
  • 616
  • 13 Jan 2022
Topic Review
Nanoparticle-Based Drug Delivery Risks
Engineered nanoparticles (NPs) with pharmacological potential can be rapidly taken up by a variety of cell types and have the potential to traverse intracellular and intercellular barriers. NPs can trigger the production of reactive oxygen species, activate the complement system, or impair the functionality of membranes and cellular barriers, depending on the kind, dose, and incubation period. These acts cause immediate or persistent damage to the organism, which can result in catastrophic consequences such as inflammation, gene mutations, and severe organ damage.
  • 615
  • 28 Apr 2023
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. 
  • 607
  • 29 Mar 2023
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. 
  • 606
  • 09 Aug 2022
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