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Topic Review
Impact of C99 on Alzheimer’s Disease
Amyloid beta (Aβ) is produced from a type-I transmembrane protein, amyloid beta precursor protein (APP). One of the APP metabolites, the 99-amino acids C-terminal fragment (C99, also called βCTF), is a direct precursor of Aβ and accumulates in the Alzheimer’s disease (AD) patient’s brain to demonstrate toxicity independent of Aβ. Conventional drug discovery strategies have focused on Aβ toxicity on the “outside” of the neuron, but C99 accumulation might explain the toxicity on the “inside” of the neuron, which was overlooked in the hypothesis. Furthermore, the common region of C99 and Aβ is a promising target for multifunctional AD drugs.
  • 1.1K
  • 21 Feb 2023
Topic Review
TRPV4 Ion Channel
The transient receptor potential vanilloid 4 channel (TRPV4) belongs to the mammalian TRP superfamily of cation channels. TRPV4 is ubiquitously expressed, activated by a disparate array of stimuli, interacts with a multitude of proteins, and is modulated by a range of post-translational modifications, the majority of which we are only just beginning to understand. Not surprisingly, a great number of physiological roles have emerged for TRPV4, as have various disease states that are attributable to the absence, or abnormal functioning, of this ion channel. This review will highlight structural features of TRPV4, endogenous and exogenous activators of the channel, and discuss the reported roles of TRPV4 in health and disease.
  • 1.1K
  • 01 Feb 2021
Topic Review
Farnesoid X Receptor
Farnesoid X receptor (FXR) has a central role in Bile Acids (BA) homeostasis and recent publications revealed that changes in autophagy due to BA-induced reactive oxygen species and increased anti-oxidant response via nuclear factor E2-related factor 2 (NRF2), result in dysregulation of FXR signaling. Several mechanistic studies have identified new dysfunctions of the cholestatic liver at cellular and molecular level, opening new venues for developing more performant therapies.
  • 1.1K
  • 12 Oct 2021
Topic Review
SUMOylation
SUMOylation is a dynamic and essential Post-Translation Modification (PTM) consisting on the conjugation of Small Ubiquitin-like Modifiers (SUMOs) to an acceptor lysine of a substrate protein. SUMOylation predominantly regulates nuclear processes and its dysregulation is associated to diseases including cancer. SUMOs share a similar three-dimensional structure with other Ubiquitin-Like Modifiers (UBLs). However, SUMOs differ due to their flexible N-terminus, which also contains the site for SUMO chain formation. All eukaryotes express at least one SUMO paralogue. Five SUMO family members have been identified in humans (SUMO1, SUMO2, SUMO3, SUMO4, and SUMO5. However, SUMO1, SUMO2, and SUMO3 are the main family members where they are commonly classified as SUMO1 and SUMO2/3 because of the high similarity between mature SUMO2 and SUMO3. All SUMO paralogues are similar in structure but differ in expression levels. SUMO2 is the most abundant family member in mammalian cells. Studies in mice show that the knockout of SUMO2 is embryonic lethal, while SUMO1 and SUMO3 knockout mice were associated to mild phenotypes, possibly because SUMO2 might compensate the loss of either SUMO1 or SUMO3. Similarly to ubiquitination, SUMO is conjugated in a in a 3-step enzymatic cascade that involves a dimeric E1 activating enzyme (SAE1 and SAE2), an E2 conjugating enzyme (Ubc9), and several SUMO E3 enzymes.
  • 1.1K
  • 28 Mar 2022
Topic Review
Cd34+ Stromal Cells/Telocytes
CD34+ stromal cells/telocytes (CD34+SCs/TCs) are an important interstitial, perivascular, peri/endoneurial and periadnexal cellular component in the dermis and hypodermis (subcutaneous adipose tissue) of the skin. Most CD34+ stromal cells are known to correspond to telocytes, a new cellular type identified by electron microscopy.
  • 1.1K
  • 29 Jul 2021
Topic Review
Oxygen Homeostasis
The unique biology of the intestinal epithelial barrier is linked to a low baseline oxygen pressure (pO2), characterised by a high rate of metabolites circulating through the intestinal blood and the presence of a steep oxygen gradient across the epithelial surface. These characteristics require tight regulation of oxygen homeostasis, achieved in part by hypoxia-inducible factor (HIF)-dependent signalling. Furthermore, intestinal epithelial cells (IEC) possess metabolic identities that are reflected in changes in mitochondrial function. In recent years, it has become widely accepted that oxygen metabolism is key to homeostasis at the mucosae. In addition, the gut has a vast and diverse microbial population, the microbiota. Microbiome–gut communication represents a dynamic exchange of mediators produced by bacterial and intestinal metabolism. The microbiome contributes to the maintenance of the hypoxic environment, which is critical for nutrient absorption, intestinal barrier function, and innate and/or adaptive immune responses in the gastrointestinal tract.
  • 1.1K
  • 22 Sep 2021
Topic Review
Botulinum Toxin Type A
Botulinum neurotoxin A (BoNT-A) which is generally known as anti-contraction of muscles has been reported as a successful treatment in various types of chronic ulcers.
  • 1.1K
  • 22 Jun 2022
Topic Review
Single B Cell Co-Expression Networks in Lung Cancer
In non-small cell lung cancer (NSCLC), there is a pressing need for immunotherapy predictive biomarkers. The processes underlying B-cell dysfunction, as well as their prognostic importance in NSCLC, are unknown. This study presents novel insights on a dysregulated B cell network that promotes proliferation in epithelial cells in NSCLC. Within this network, a nine-gene signature demonstrated prognostic and predictive indications in more than 1400 NSCLC patients using their gene and protein expression profiles in bulk tumors. Multiple genes (HLA-DRA, HLA-DRB1, OAS1, and CD74) differentially expressed in NSCLC B cells, peripheral blood lymphocytes, and tumor T cells had concordant prognostic indications at mRNA and protein expression levels. 
  • 1.1K
  • 28 Jun 2022
Topic Review
Doxorubicin-Induced Mitochondrial Dysfunction
Cardiotoxicity has emerged as a major side effect of doxorubicin (DOX) treatment, affecting nearly 30% of patients within 5 years after chemotherapy. Heart failure is the first non-cancer cause of death in DOX-treated patients. 
  • 1.1K
  • 08 Jul 2022
Topic Review
Intestinal Cell Plasticity
Under constant barrage from chemical, pathogenic, and mechanical stresses, the intestinal epithelium is homeostatically replenished by a pool of Lgr5⁺ intestinal stem cells (ISCs), residing at the bottom of submucosal invaginations termed crypts. Decorated with the RSPO-receptor LGR5, which potentiates canonical Wnt/β-catenin signalling, these actively cycling cells can both self-renew and give rise to short-lived transit-amplifying cells. In turn, transit-amplifying cells undergo successive rounds of cell division and differentiation to generate the full gamut of terminally differentiated intestinal cell types tasked with performing pleiotropic absorptive, secretory, immune, and barrier functions. The self-renewal capabilities and multipotency of Lgr5⁺ ISCs are tightly controlled by instructive cues emanating from epithelial and stromal components of the ISC niche in the vicinity of the lower crypt.  The intestinal epithelium displays a remarkable ability to regenerate following demise of homeostatic Lgr5⁺ ISCs post injury. Plasticity—the ability of lineage-restricted cells to regain self-renewal capacity and multi-lineage differentiation potential in response to environmental cues—is pervasive among multiple intestinal cell populations. Reserve stem-like cells, lineage-committed progenitors, and/or fully differentiated cell types can all contribute to regeneration and repair through dedifferentiation and reversion to an Lgr5⁺ stem-like state. In line with the pervasive plasticity of the intestinal epithelium, accumulating evidence supports both “bottom-up” and “top-down” histogenesis of colorectal tumours whereby the cells-of-origin comprise either ISCs at the crypt base or differentiated cells at the crypt apex, respectively. 
  • 1.1K
  • 30 Mar 2021
Topic Review
Metabolic Regulation of Mitochondrial Protein Biogenesis in neurons
Neurons critically depend on mitochondria for ATP production and Ca2+ buffering. They are highly compartmentalized cells and therefore a finely tuned mitochondrial network constantly adapting to the local requirements is necessary. For neuronal maintenance, old or damaged mitochondria need to be degraded, while the functional mitochondrial pool needs to be replenished with freshly synthesized components. Mitochondrial biogenesis is known to be primarily regulated via the PGC-1α-NRF1/2-TFAM pathway at the transcriptional level. However, while transcriptional regulation of mitochondrial genes can change the global mitochondrial content in neurons, it does not explain how a morphologically complex cell like a neuron adapts to local differences in mitochondrial demand. 
  • 1.1K
  • 07 Nov 2022
Topic Review
Myofibroblasts
Myofibroblasts are contractile, α-smooth muscle actin-positive cells with multiple roles in pathophysiological processes. Myofibroblasts mediate wound contractions, but their persistent presence in tissues is central to driving fibrosis, making them attractive cell targets for the development of therapeutic treatments. However, due to shared cellular markers with several other phenotypes, the specific targeting of myofibroblasts has long presented a scientific and clinical challenge.
  • 1.1K
  • 11 Aug 2023
Topic Review
Lipid-Based mRNA Nanoparticles
Messenger RNA (mRNA) is being extensively used in gene therapy and vaccination due to its safety over DNA, in the following ways: its lack of integration risk, cytoplasmic expression, and transient expression compatible with fine regulations. However, clinical applications of mRNA are limited by its fast degradation by nucleases, and the activation of detrimental immune responses. Advances in mRNA applications, with the recent approval of COVID-19 vaccines, were fueled by optimization of the mRNA sequence and the development of mRNA delivery systems. Although delivery systems and mRNA sequence optimization have been abundantly reviewed, understanding of the intracellular processing of mRNA is mandatory to improve its applications. 
  • 1.1K
  • 12 Jul 2021
Topic Review
Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune liver disease characterized by inflammation and damage of small bile ducts that frequently progress to liver cirrhosis and predominantly affects females. The key moment in the pathophysiology of the disease is loss of tolerance to PDC-E2, pyruvate subunit of the complex of dehydrogenase enzyme, located in the mitochondrial membrane. Combined genetic, epigenetic and environmental factors trigger the initial damage of the biliary epithelium in PBC, followed by the multilineage immune/inflammatory response to damaged cholangiocytes resulting in development of chronic biliary inflammatory disease.
  • 1.1K
  • 27 Oct 2020
Topic Review
L-Lactate
l-Lactate plays a role as a metabolic and signaling molecule, accordingly, Vaccari-Cardoso and co-workers developed a viral vector to express a modified version of lactate oxidase (LOx) originating from the bacteria Aerococcus viridans. Their results in vitro show that LOx expression in astrocytes reduced their intracellular lactate levels and its release to the extracellular space.
  • 1.1K
  • 07 Oct 2021
Topic Review
WWOX Controls Cell Survival, Immune Response, Disease Progression
Tumor suppressor WWOX inhibits cancer growth and retards Alzheimer’s disease (AD) progression. Supporting evidence shows that the more strongly WWOX binds intracellular protein partners, the weaker is cancer cell growth in vivo. Whether this correlates with retardation of AD progression is unknown. Two functional forms of WWOX exhibit opposite functions. pY33-WWOX is proapoptotic and anticancer, and is essential for maintaining normal physiology. 
  • 1.1K
  • 14 Jul 2022
Topic Review
P2X7 Variants
The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants’ different roles and their implications in pathological conditions, including oncogenesis. Our article on P2X7 variants in oncogenesis recently published in Cells gives an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions. Here you find the main structural information on P2X7 variants.
  • 1.1K
  • 02 Feb 2021
Topic Review
Sarcoma Metabolomics
Sarcoma metabolomics is a broadly unexplored field that can offer diverse opportunities. Deeper characterization and a sharper picture of sarcoma metabolic and microenvironment landscape may pave the way for diagnostic and staging refinement and identification of new potential therapeutic targets, resulting in benefits for patients.
  • 1.1K
  • 02 Jul 2021
Topic Review
HFpEF
Heart failure (HF) with preserved left ventricular ejection fraction (HFpEF) is becoming the predominant form of HF. However, medical therapy that improves cardiovascular outcome in HF patients with almost normal and normal systolic left ventricular function, but diastolic dysfunction is missing. The cause of this unmet need is incomplete understanding of HFpEF pathophysiology, the heterogeneity of the patient population, and poor matching of therapeutic mechanisms and primary pathophysiological processes.
  • 1.1K
  • 11 Mar 2022
Topic Review
Bacteria-Based Cancer Treatment
Cancer refers to a disease involving abnormal cells that proliferate uncontrollably and can invade normal body tissue. It was estimated that at least 9 million patients are killed by cancer annually. Recent studies have demonstrated that bacteria play a significant role in cancer treatment and prevention. Owing to its unique mechanism of abundant pathogen-associated molecular patterns in antitumor immune responses and preferentially accumulating and proliferating within tumors, bacteria-based cancer immunotherapy has recently attracted wide attention.
  • 1.1K
  • 31 Oct 2022
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