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Topic Review
Sigma Receptors in Iron/Heme Homeostasis and Ferroptosis
Sigma receptors are non-opiate/non-phencyclidine receptors that bind progesterone and/or heme and also several unrelated xenobiotics/chemicals. They reside in the plasma membrane and in the membranes of the endoplasmic reticulum, mitochondria, and nucleus. The biology/pharmacology of these proteins focused primarily on their role in neuronal functions in the brain/retina. However, there have been developments in the field with the discovery of unexpected roles for these proteins in iron/heme homeostasis. Sigma receptor 1 (S1R) regulates the oxidative stress-related transcription factor NRF2 and protects against ferroptosis, an iron-induced cell death process. Sigma receptor 2 (S2R), which is structurally unrelated to S1R, complexes with progesterone receptor membrane components PGRMC1 and PGRMC2. S2R, PGRMC1, and PGRMC2, either independently or as protein–protein complexes, elicit a multitude of effects with a profound influence on iron/heme homeostasis. This includes the regulation of the secretion of the iron-regulatory hormone hepcidin, the modulation of the activity of mitochondrial ferrochelatase, which catalyzes iron incorporation into protoporphyrin IX to form heme, chaperoning heme to specific hemoproteins thereby influencing their biological activity and stability, and protection against ferroptosis.
  • 544
  • 19 Oct 2023
Topic Review
Zinc Transporters in Different Biological Kingdoms
Zinc transporters take up/release zinc ions (Zn2+) across biological membranes and maintain intracellular and intra-organellar Zn2+ homeostasis. Since this process requires a series of conformational changes in the transporters, detailed information about the structures of different reaction intermediates is required for a comprehensive understanding of their Zn2+ transport mechanisms. Various Zn2+ transport systems have been identified in bacteria, yeasts, plants, and humans. 
  • 544
  • 12 Mar 2024
Topic Review
Direct Interaction between Sphingolipids and SNAREs
The fusion of membranes is a central part of the physiological processes involving the intracellular transport and maturation of vesicles and the final release of their contents, such as neurotransmitters and hormones, by exocytosis. Traditionally lipids have been regarded as structural elements playing a relatively minor role in the molecular mechanisms of exocytosis whereas proteins such as SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors) are thought to be the central elements that generate the specificity and force needed for overcoming the repulsion of the negative charges within lipid bilayers that oppose fusion. The effect of sphingosine and synthetic derivatives on the heterologous and homologous fusion of organelles can be considered as a new mechanism of action of sphingolipids influencing important physiological processes, which could underlie therapeutic uses of sphingosine derived lipids in the treatment of neurodegenerative disorders and cancers of neuronal origin such neuroblastoma. 
  • 542
  • 15 Feb 2022
Topic Review
The Roles of MicroRNAs in Obesity
Obesity has become a global epidemic, contributing to the development of numerous chronic diseases, including diabetes, chronic kidney disease (CKD) and cardiovascular disorders. MicroRNAs (miRNAs) have emerged as key regulators in various biological processes, including metabolism, inflammation, and tissue remodeling, making them pivotal players in obesity-related pathologies. 
  • 541
  • 24 Oct 2023
Topic Review
Targeting Signalling Pathways in Chronic Wound Healing
Chronic wounds fail to achieve complete closure and are an economic burden to healthcare systems due to the limited treatment options and constant medical attention. Chronic wounds are characterised by dysregulated signalling pathways.
  • 541
  • 04 Jan 2024
Topic Review
Role of Dioxygen in Microbial Bio-Oxygenation
Dioxygen (O2, more commonly referred to as molecular oxygen) is the only element in the Earth’s environment that is paramagnetic in its ground-state. Dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of bio-oxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis and in facilitating reactions that help to drive the global geochemical carbon cycle. 
  • 541
  • 18 Mar 2024
Topic Review
Crosstalk among Calcium ATPases
Ca2+-ATPases are key components of Ca2+ extrusion machinery and thus are pivotal for preservation of neuronal function.
  • 541
  • 26 Apr 2021
Topic Review
MicroRNA Let-7-Mediated Glycolysis
The microRNA (miRNA) Let-7 has been identified as related to glycolysis procedures such as tissue repair, stem cell-derived cardiomyocytes, and tumoral metastasis. In many cancers, the expression of glycolysis-related enzymes is correlated with Let-7, in which multiple enzymes are related to the regulation of the autophagy process. However, much recent research has not comprehensively investigated how Let-7 participates in glycolytic reprogramming or its links to autophagic regulations, mainly in tumor progression.
  • 539
  • 11 Jan 2022
Topic Review
Small Heat Shock Proteins in Cancer Therapy
Small heat shock proteins (sHSPs) are ubiquitous ATP-independent chaperones that play essential roles in response to cellular stresses and protein homeostasis. sHSPs are ubiquitously expressed in numerous types of tumors, and their expression is closely associated with cancer progression. sHSPs have been suggested to control a diverse range of cancer functions, including tumorigenesis, cell growth, apoptosis, metastasis, and chemoresistance, as well as regulation of cancer stem cell properties. 
  • 538
  • 23 Sep 2022
Topic Review
Early Diagnosis of Neurodegenerative Diseases
Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble β-sheet-rich fibrils, which ultimately lead to neurotoxicity and cell death. After a hundred years of research on the subject, this is the only reliable histopathological feature in our hands. Since AD and PD are diagnosed only once neuronal death and the first symptoms have appeared, the early detection of these diseases is currently impossible. Several reasons could be associated with the lack of effective therapeutic treatments. One of the most important factors is the lack of selective probes capable of detecting, as early as possible, the most toxic amyloid species involved in the onset of these pathologies. In this regard, chemical probes able to detect and distinguish among different amyloid aggregates are urgently needed. 
  • 538
  • 22 Feb 2024
Topic Review
Molecular Mechanisms Driving the Formation of Brain Metastases
Targeted therapies for cancers have improved primary tumor response rates, but concomitantly, brain metastases (BM) have become the most common brain tumors in adults and are associated with a dismal prognosis of generally less than 6 months, irrespective of the primary cancer type. They most commonly occur in patients with primary breast, lung, or melanoma histologies; however, they also appear in patients with other primary cancers including, but not limited to, prostate cancer, colorectal cancer, and renal cell carcinoma. Historically, molecular biomarkers have normally been identified from primary tumor resections. However, clinically informative genomic alterations can occur during BM development and these potentially actionable alterations are not always detected in the primary tumor leading to missed opportunities for effective targeted therapy. 
  • 534
  • 20 Dec 2022
Topic Review
The Mammalian Thioredoxin Reductase Probes
The cardinal component of the thioredoxin system, mammalian thioredoxin reductase (TrxR) plays a vital role in supporting various physiological functions; however, its malfunction, disrupting redox balance, is intimately associated with the pathogenesis of multiple diseases. Fluorescent probes offer several advantages for in situ imaging and the quantification of biological targets, such as non-destructiveness, real-time analysis, and high spatiotemporal resolution. These benefits facilitate the transition from a poise to a flux understanding of cellular targets, further advancing scientific studies in related fields. The TrxR fluorescent probes have contributed significantly to the investigation of TrxR’s biological functions and have been valuable tools in TrxR-related research.
  • 534
  • 24 Aug 2023
Topic Review
New Therapeutic Interventions for Kidney Carcinoma
Renal cell carcinoma (RCC) in metastatic form is a lethal pathology difficult to treat; therefore, the research of new therapeutic options for the treatment of metastatic patients is crucial to improve quality of life and overall survival.
  • 533
  • 08 Oct 2022
Topic Review
H2S in Oncological Disorders and Non-Coding RNAs Regulation
H2S is colorless, flammable, and water-soluble gas with a characteristic smell of rotten eggs; it is now widely recognized as an endogenous biological mediator. Since its discovery, H2S has been found to have vital functions in various physiological and pathological conditions. Non-coding RNAs (ncRNAs) form a relatively recent class of post-transcriptional regulators that is widely expanding. Non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases.
  • 532
  • 05 Feb 2024
Topic Review
Isoprene-Derived Signaling Molecules in Plant System
Isoprene, a lipophilic and unstable compound with the chemical formula C5H8, is transported to plant chloroplasts via the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, which relies on photosynthesis. Although only about 20% of terrestrial plants can synthesize isoprene, those that emit it are more adaptable to oxidative and thermal stresses. Plants use volatile organic compounds (VOCs) to communicate with other living things. Isoprene, monoterpenes and sesquiterpenes make up the largest class of volatile organic compounds (VOCs) emitted by plants terpenes. In plant–plant interactions, mono- and sesquiterpenes are well-known communication molecules. On the other hand, isoprene, the smallest and most often released terpene, is instead given a role in fighting abiotic stressors. 
  • 530
  • 22 Mar 2024
Topic Review
MALAT-1 Modulates Epithelial–Mesenchymal Transition in Cancer
Metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) is a long intergenic non-coding RNA (lncRNA) located on chr11q13. It is overexpressed in several cancers and controls gene expression through chromatin modification, transcriptional regulation, and post-transcriptional regulation. Importantly, MALAT-1 stimulates cell proliferation, migration, and metastasis and serves a vital role in driving the epithelial-to-mesenchymal transition (EMT), subsequently acquiring cancer stem cell-like properties and developing drug resistance. MALAT-1 modulates EMT by interacting with various intracellular signaling pathways, notably the phosphoinositide 3-kinase (PI3K)/Akt and Wnt/β-catenin pathways. It also behaves like a sponge for microRNAs, preventing their interaction with target genes and promoting EMT. 
  • 529
  • 18 Jan 2024
Topic Review
Molecular Characteristics of Triple-Negative Breast Cancer
Researchers have investigated the molecular mechanisms of breast cancer initiation and progression, especially triple-negative breast cancer (TNBC), in order to identify specific biomarkers that could serve as feasible targets for innovative therapeutic strategies development. TNBC is characterized by a dynamic and aggressive nature, due to the absence of estrogen, progesterone and human epidermal growth factor 2 receptors.
  • 528
  • 16 Feb 2023
Topic Review
PD-1 Blocking Therapy in CC
Current therapies have vastly improved the clinical outcomes of cervical cancer patients, but progress in new systemic treatment modalities has been slow in the last years. Especially for patients with advanced disease this is discouraging, as their prognosis remains very poor. The pathogen-induced nature, the considerable mutational load, the involvement of genes regulating the immune response, and the high grade of immune infiltration, suggest that immunotherapy might be a promising strategy to treat cervical cancer.
  • 527
  • 18 Mar 2021
Topic Review
NF-κB in Microglia/Macrophages of GBM and AD
Microglia and macrophages are pivotal to the brain’s innate immune response and have garnered considerable attention in the context of glioblastoma (GBM) and Alzheimer’s disease (AD) research.  The NF-κB pathway, first identified in 1986 by Sen and Baltimore, plays a pivotal role in the immune response, cell proliferation, and apoptosis. Its molecular architecture includes five DNA-binding members: REL (c-REL), RELA (p65), RELB, NF-κB1 (p50), and NF-κB2 (p52), with the unique attribute of NF-κB2 (p52) lacking transactivation domains. NF-κB signaling encompasses three distinct pathways: canonical, non-canonical, and atypical, each with unique activation mechanisms and cellular responses. Through multiple graphic depictions, the reference clearly presented the traditional pathways and components of NF-κB. The canonical pathway, generally activated by microbial infections or pro-inflammatory cytokines, involves the phosphorylation and subsequent degradation of IκB proteins by the IκB kinase (IKK) complex, releasing p65/p50 NF-κB dimers for nuclear translocation and transcription activation. The non-canonical pathway, selectively activated by receptors like CD40, B-cell-activating factor receptor (BAFF-R), and lymphotoxin beta receptor (LTβR), primarily involves NF-κB2 (p100/p52) proteins and RELB. This pathway initiates with ligand binding, triggering NF-κB-inducible kinase (NIK) to phosphorylate and activate IKK1 (IKKα), leading to p100’s processing into p52 and the subsequent translocation of p52/RELB dimers to the nucleus, thus regulating gene expression differently compared to the canonical pathway. The atypical pathway, which is less well-characterized, can be triggered by DNA-damaging agents independently of IKK, illustrating the versatility and complexity of NF-κB signaling in cellular dynamics.
  • 525
  • 28 Dec 2023
Topic Review
Biogenesis and Expression at PMs of GPI-APs
Glycosylphosphatidylinositol (GPI)-anchored proteins (APs) are produced by coupling of the completed GPI anchor, prefabricated by stepwise transfer from activated precursors of the corresponding carbohydrate and phosphoethanolamine (EtN-P) residues to PI at the luminal face of the ER membranes, to the carboxy-terminus of the polypeptide precursor moiety upon its translation and transient arrest at the endoplasmic reticulum (ER) membranes.
  • 521
  • 05 Jun 2023
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