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Topic Review
RAD52 in Genome Maintenance
The maintenance of genome integrity is critical for cell survival. Homologous recombination (HR) is considered the major error-free repair pathway in combatting endogenously generated double-stranded lesions in DNA. Nevertheless, a number of alternative repair pathways have been described as protectors of genome stability, especially in HR-deficient cells. One of the factors that appears to have a role in many of these pathways is human RAD52, a DNA repair protein that was previously considered to be dispensable due to a lack of an observable phenotype in knock-out mice. In later studies, RAD52 deficiency has been shown to be synthetically lethal with defects in BRCA genes, making RAD52 an attractive therapeutic target, particularly in the context of BRCA-deficient tumors.
  • 856
  • 14 Sep 2021
Topic Review
Neutrophil Interactions with Lymphatic System
The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues.
  • 856
  • 19 Jan 2022
Topic Review
CD137+ T-Cells
The CD137 receptor is expressed by activated antigen-specific T-cells. CD137+ T-cells were identified inside TILs and PBMCs of different tumor types and have proven to be the naturally occurring antitumor effector cells, capable of expressing a wide variability in terms of TCR specificity against both shared and neoantigenic tumor-derived peptides. The aim of this review is thus summarizing and highlighting their role as drivers of patients’ immune responses in anticancer therapies as well as their potential role in future and current strategies of immunotherapy.
  • 855
  • 08 Mar 2021
Topic Review
Liquid–Liquid Phase Separation in Cancer Signaling
The process of LLPS(liquid–liquid phase separation (LLPS) is favored by multivalent interactions between specific protein domains, intrinsically disordered regions in proteins (IDR) and nucleic acids.
  • 855
  • 20 Apr 2022
Topic Review
Industrial Enyzmes
Industrial enzymes are enzymes that are commercially used in a variety of industries such as pharmaceuticals, chemical production, biofuels, food & beverage, and consumer products. Due to advancements in recent years, biocatalysis through isolated enzymes is considered more economical than use of whole cells. Enzymes may be used as a unit operation within a process to generate a desired product, or may be the product of interest. Industrial biological catalysis through enzymes has experienced rapid growth in recent years due to their ability to operate at mild conditions, and exceptional chiral and positional specificity, things that traditional chemical processes lack. Isolated enzymes are typically used in hydrolytic and isomerization reactions. Whole cells are typically used when a reaction requires a co-factor. Although co-factors may be generated in vitro, it is typically more cost-effective to use metabolically active cells.
  • 855
  • 20 Oct 2022
Topic Review
TP53 and Testicular Germ Cell Tumors
Germ cell tumors (GCTs) are the most common solid malignancies in young men. Despite the high frequency of these cancers within this defined age group, the discovery of the exceptional sensitivity of these tumors to the platinum DNA crosslinking compound cisplatin has led to the survival of most patients, with the current five-year survival rate exceeding 95%.
  • 854
  • 05 Nov 2021
Topic Review
Neuronal Autophagy
Autophagy is a major degradative pathway that plays a key role in sustaining cell homeostasis, integrity, and physiological functions. Macroautophagy, which ensures the clearance of cytoplasmic components engulfed in a double-membrane autophagosome that fuses with lysosomes, is orchestrated by a complex cascade of events. Autophagy has a particularly strong impact on the nervous system, and mutations in core components cause numerous neurological diseases. 
  • 853
  • 19 Jan 2024
Topic Review
Ultrasound-Mediated Drug Delivery and Gene Therapy
Ultrasound (US) is a nearly innocuous and widely available imaging technique with a well-established role in various diagnostic applications. Diagnostic US techniques uses high frequency ultrasound waves to view real-time tissue and organs inside the human body. The use of US as a drug delivery facilitator was first described in the mid 90s, using the physical transient increased cell membrane permeability from sonoporation. Subsequent research reported the enhanced biophysical effects of ultrasound by incorporation of MBs.
  • 852
  • 05 Nov 2021
Topic Review
Diverse Calpain Family in Trypanosomatidae
The Trypanosomatidae family, class Kinetoplastea, encompasses exclusively parasitic protozoa, some of which cause important human diseases. About 37 million people worldwide are infected either with Trypanosoma brucei, the etiological agent of African sleeping sickness; Trypanosoma cruzi, the causative agent of Chagas disease; or with different species of the genus Leishmania, responsible for different clinical manifestations known as leishmaniasis. The current therapy to treat these diseases is unsatisfying due to their low efficacy, high cost, toxicity, and tough administration routes, like parenteral. Therefore, the search for more effective drugs is still an urgent need, which can lead to alternative strategies, such as a repurposed approach with compounds already approved for human usage. In view of this scenario, calpains are an interesting target due to the intense efforts to develop means of identifying selective inhibitors in this group of calcium-dependent cysteine peptidases. Since these enzymes are involved in crucial physiological roles in mammals, their deregulated activity is implicated in several pathophysiological processes, especially in fibrotic diseases and neurological disorders. Moreover, trypanosomatids harbor a large and diverse family of calpain sequences in their genomes, comprising a wide range of associated domains, differential gene expression among life-cycle forms, and ubiquitous distribution in the parasite cell body. However, due to the difficulties in assaying calpain activity in these microorganisms, there is still an open question: are trypanosomatid calpains proteolytically active?
  • 850
  • 13 Apr 2021
Topic Review
Germ Cell Derivation from PSCs
Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising technology to overcome infertility, particularly germ cell aplasia. Early germ cells, such as primordial germ cells, can be relatively easily derived from pluripotent stem cells (PSCs); however, further progression to post-meiotic germ cells usually requires a gonadal niche and signals from gonadal somatic cells.
  • 849
  • 22 Sep 2021
Topic Review
ER Stress Responses
The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in all ER components and machineries. The ER stress sensor pathways, including IRE1/sXBP1, PERK/EIf2α and ATF6, orchestrate the major regulatory circuits to ensure ER homeostasis. The embryonic or postnatal lethality that occurs upon genetic depletion of these sensors reveals the essential role of the ER stress pathway in cell biology. In contrast, the impairment or excessive activation of ER stress has been reported to cause or aggravate several diseases such as atherosclerosis, diabetes, NAFDL/NASH, obesity and cancer. Being part of innate immunity, myeloid cells are the first immune cells entering the inflammation site. Upon entry into a metabolically stressed disease environment, activation of ER stress occurs within the myeloid compartment, leading to the modulation of their phenotype and functions.
  • 847
  • 26 May 2021
Topic Review
S100P-Induced Cell Migration and Metastasis
The presence of S100P protein in cancer cells is strongly associated with reduced survival times of patients suffering from a number of cancers. It has been shown previously that S100P is a potent inducer of metastasis in a model system and it is likely that this metastasis-inducing ability underlies its association with reduced patient survival. However, the molecular mechanisms involved in S100P-driven metastasis are only now beginning to be elucidated and the evidence points to S100P enhancing cell migration and cell invasion.  It is now shown that in the same cell system S100P enhances cell migration by two separate mechanisms. One pathway being intracellular, involves changes in the numbers of focal adhesions.  The second pathway occurs at the cell membrane and does not involve changes in the number of focal adhesions, but involves extracellular/membrane bound S100P and is inhibited by specific inhibitors of plasmin. Importantly, mutation of the C-terminal amino acid of S100P, not only abolishes both pathways, but also markedly reduces the metastasis-inducing ability of S100P, thus identifying a possible target for the reduction of S100P-induced metastasis.
  • 847
  • 27 Oct 2021
Topic Review
Endogenous Opioids and Stem Cells
Opioids are considered the oldest drugs known by humans and have been used for sedation and pain relief for several centuries. Nowadays, endogenous opioid peptides are divided into four families: enkephalins, dynorphins, endorphins, and nociceptin/orphanin FQ. They exert their action through the opioid receptors (ORs), transmembrane proteins belonging to the su-per-family of G-protein-coupled receptors, and are expressed throughout the body; the receptors are the δ opioid receptor (DOR), μ opioid receptor (MOR), κ opioid receptor (KOR), and nociceptin/orphanin FQ receptor (NOP). Endogenous opioids are mainly studied in the central nervous system (CNS), but their role has been investigated in other organs, both in physiological and in pathological conditions. Here, it is presented a revision of their role in stem cell (SC) biology, since these cells are a subject of great scientific interest due to their peculiar features and their involvement in cell-based therapies in regenerative medicine. In particular, it will be focused on the endogenous opioids’ ability to modulate SC proliferation, stress response (to oxidative stress, starvation, or damage following ischemia–reperfusion), and differentiation towards different lineages, such as neuro-genesis, vasculogenesis, and cardiogenesis.
  • 847
  • 28 Jun 2022
Topic Review
The Endocannabinoid System and Kidney Disease
The endocannabinoid system (ECS) is an important signaling pathway that involves the binding of lipid ligands, known as cannabinoids, to cannabinoid receptors, and it encompasses, as well, the metabolic enzymes of endocannabinoids. Endocannabinoid signaling plays crucial roles in human physiology in the function of multiple systems. The two cannabinoid receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), are cell membrane proteins that interact with both exogenous and endogenous bioactive lipid ligands, or endocannabinoids. The evidence has established that endocannabinoid signaling operates within the human kidney, as well as suggests the important role it plays in multiple renal pathologies. 
  • 847
  • 23 May 2023
Topic Review
Thymic Aging Associated with COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19) and particularly exhibits severe symptoms and mortality in elderly individuals. Mounting evidence shows that the characteristics of the age-related clinical severity of COVID-19 are attributed to insufficient antiviral immune function and excessive self-damaging immune reaction, involving T cell immunity and associated with pre-existing basal inflammation in the elderly. Age-related changes to T cell immunosenescence is characterized by not only restricted T cell receptor (TCR) repertoire diversity, accumulation of exhausted and/or senescent memory T cells, but also by increased self-reactive T cell- and innate immune cell-induced chronic inflammation, and accumulated and functionally enhanced polyclonal regulatory T (Treg) cells. Many of these changes can be traced back to age-related thymic involution/degeneration. How these changes contribute to differences in COVID-19 disease severity between young and aged patients is an urgent area of investigation.
  • 847
  • 28 Apr 2021
Topic Review
Organic Small Molecules in Pain-Management
There are different types of anti-inflammatory agents, including small molecules, peptides, and antibodies. In this entry, there will be a focus on small molecules for anti-inflammatory treatments as they have been the center of traditional medicine. Small molecule drugs are compounds with low molecular weight that can easily enter the body and modulate biochemical processes to treat medical conditions.
  • 846
  • 13 Jul 2021
Topic Review
Beta-ketoacyl-(acyl-carrier-protein) Synthase III
In enzymology, a β-ketoacyl-[acyl-carrier-protein] synthase III (EC 2.3.1.180) is an enzyme that catalyzes the chemical reaction Thus, the two substrates of this enzyme are acetyl-CoA and malonyl-[acyl-carrier-protein], whereas its 3 products are acetoacetyl-[acyl-carrier-protein], CoA, and CO2. This enzyme belongs to the family of transferases, to be specific those acyltransferases transferring groups other than aminoacyl groups. This enzyme participates in fatty acid biosynthesis. β-Ketoacyl-acyl-carrier-protein synthase III is involved in the dissociated (or type II) fatty-acid biosynthesis system that occurs in plants and bacteria. The role of FabH in fatty acid synthesis has been described in Streptomyces glaucescens, Streptococcus pneumoniae, and Streptomyces coelicolor.
  • 846
  • 03 Nov 2022
Topic Review
Energy-Saving Mechanism in Skeletal Muscle
Exercise produces oxidants from a variety of intracellular sources, including NADPH oxidases (NOX) and mitochondria. Exercise-derived reactive oxygen species (ROS) are beneficial, and the amount and location of these ROS is important to avoid muscle damage associated with oxidative stress.
  • 845
  • 22 Aug 2023
Topic Review
B Cells in Autoimmunity
B cells are key players in this relationship because activated and differentiated B cells produce secretory immunoglobulin A (sIgA), which binds commensal bacteria to preserve a healthy microbial ecosystem.
  • 844
  • 18 May 2021
Topic Review
Agonists for Peroxisome Proliferator-Activated Receptors
Nuclear receptors (NRs) are ligand-dependent transcription factors that modulate diverse aspects of development, reproduction, and energy homeostasis. This receptor superfamily includes receptors for vitamin D, steroid hormones, thyroid hormones and retinoids, as well as a large number of orphan receptors. NRs are composed of six functionally distinct regions (termed A to F). The N-terminal AB region is highly variable and contains a constitutionally active transactivation function-1 (AF-1) motif. The central C region (a DNA-binding region) is highly conserved among NRs and contains two zinc finger motifs that make contact with specific nucleotide sequences, termed hormone response elements. The C-terminal D, E and F regions are required for ligand binding and receptor dimerization. In most NRs, these regions also contain a second highly conserved transcriptional activation function-2 (AF-2) motif, which is important for ligand-dependent transcription.
  • 844
  • 07 Sep 2021
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