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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. 
  • 536
  • 12 Mar 2024
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.
  • 535
  • 11 Jan 2022
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. 
  • 535
  • 18 Mar 2024
Topic Review
Redox-Related Proteins in Melanoma Progression
Melanoma is the most aggressive type of skin cancer. Despite the available therapies, the minimum residual disease is still refractory. Reactive oxygen and nitrogen species (ROS and RNS) play a dual role in melanoma, where redox imbalance is involved from initiation to metastasis and resistance. Redox proteins modulate the disease by controlling ROS/RNS levels in immune response, proliferation, invasion, and relapse. Chemotherapeutics such as BRAF and MEK inhibitors promote oxidative stress, but high ROS/RNS amounts with a robust antioxidant system allow cells to be adaptive and cooperate to non-toxic levels. These proteins could act as biomarkers and possible targets. By understanding the complex mechanisms involved in adaptation and searching for new targets to make cells more susceptible to treatment, the disease might be overcome. 
  • 534
  • 07 Mar 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. 
  • 533
  • 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. 
  • 533
  • 22 Feb 2024
Topic Review
Immunometabolism of Myeloid-Derived Suppressor Cells in Oncology
The field of immunometabolism seeks to decipher the complex interplay between the immune system and the associated metabolic pathways. The role of small molecules that can target specific metabolic pathways and subsequently alter the immune landscape provides a desirable platform for new therapeutic interventions. Immunotherapeutic targeting of suppressive cell populations, such as myeloid-derived suppressor cells (MDSC), by small molecules has shown promise in pathologies such as cancer and support testing of similar host-directed therapeutic approaches in MDSC-inducing conditions such as tuberculosis (TB). MDSC exhibit a remarkable ability to suppress T-cell responses in those with TB disease. In tumors, MDSC exhibit considerable plasticity and can undergo metabolic reprogramming from glycolysis to fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) to facilitate their immunosuppressive functions.
  • 529
  • 31 Mar 2022
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.
  • 529
  • 08 Oct 2022
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.
  • 528
  • 04 Jan 2024
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.
  • 526
  • 18 Mar 2021
Topic Review
Crosstalk among Calcium ATPases
Ca2+-ATPases are key components of Ca2+ extrusion machinery and thus are pivotal for preservation of neuronal function.
  • 526
  • 26 Apr 2021
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.
  • 526
  • 05 Feb 2024
Topic Review
Action of lncRNAs Mediated by RBPs in NSCLC
LncRNAs can alter gene expression and/or its functions by acting as miRNA spongers, via a direct interaction of lncRNAs with mRNAs or binding to RNA-binding proteins (RBPs). RBPs were shown to regulate mRNA expression and stability at the post-transcriptional level. RBPs combine a flexible structure with a versatile RNA-binding domain. These properties allow RBPs to engage in highly dynamic interactions both with other proteins as well as with coding and non-coding RNAs, leading to ribonucleoprotein complexes (RNPs) being formed. RNPs regulate RNA splicing, polyadenylation, stability, localization, translation, and degradation. In non-small-cell lung cancer (NSCLC), lncRNAs can regulate the levels and stability of target mRNAs by binding RBPs to form RNP complexes, as was demonstrated in a number of examples.
  • 525
  • 06 Sep 2023
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.
  • 522
  • 24 Aug 2023
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. 
  • 520
  • 22 Mar 2024
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.
  • 519
  • 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.
  • 518
  • 05 Jun 2023
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.
  • 516
  • 16 Feb 2023
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. 
  • 515
  • 18 Jan 2024
Topic Review
Epithelioid Haemangioendothelioma
Epithelioid haemangioendothelioma (EHE) is an ultra-rare malignant vascular tumour with a prevalence of 1 per 1,000,000. It develops from endothelial cells, which are the cells that line all blood vessels in the body. Therefore, it typically expresses endothelial cell markers. It can also be identified through analysis of the genes. Two genes, WWTR1 and CAMTA1, are broken and fused together in 90% of cases. Alternatively, in approximately 10% of cases, the genes that are broken and fused together are YAP1 and TFE3. 
  • 512
  • 16 Oct 2023
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