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Topic Review
The Importance of Organoids for One Health
One Health describes the importance of considering humans, animals, and the environment in health research. One Health and the 3R concept, i.e., the replacement, reduction, and refinement of animal experimentation, shape today’s research more and more. The development of organoids from many different organs and animals led to the development of highly sophisticated model systems trying to replace animal experiments. Organoids may be used for disease modelling in various ways elucidating the manifold host–pathogen interactions. 
  • 668
  • 28 Sep 2022
Topic Review
The HSC Niche in β-thalassemia and SCD
Hemoglobinopathies are inherited disorders affecting hemoglobin (Hb) production, estimated to be the most common monogenic diseases worldwide. In the last decade, research on pathophysiology and therapeutic solutions for β-thalassemia (BThal) and sickle cell disease (SCD) has been mostly focused on the primary erythroid defect, thus neglecting the study of hematopoietic stem cells (HSCs) and bone marrow (BM) microenvironment. The quality and engraftment of HSCs depend on the BM microenvironment, influencing the outcome of HSC transplantation (HSCT) both in allogeneic and in autologous gene therapy settings. In BThal and SCD, the consequences of severe anemia alter erythropoiesis and cause chronic stress in different organs, including the BM. 
  • 547
  • 07 Jul 2022
Topic Review
The HIF-1α and Gastric Cancer
Gastric cancer is one of the most aggressive tumors in the clinic that is resistant to chemotherapy. Gastric tumors are rich in hypoxic niches, and high expression of hypoxia-inducible factor-1α is associated with poor prognosis. Hypoxia is the principal architect of the topographic heterogeneity in tumors. Hypoxia-inducible factor-1α (HIF-1α) reinforces all hallmarks of cancer and donates cancer cells with more aggressive characteristics at hypoxic niches. HIF-1α potently induces sustained growth factor signaling, angiogenesis, epithelial–mesenchymal transition, and replicative immortality. Hypoxia leads to the selection of cancer cells that evade growth suppressors or apoptotic triggers and deregulates cellular energetics. HIF-1α is also associated with genetic instability, tumor-promoting inflammation, and escape from immunity. 
  • 501
  • 17 Jun 2022
Topic Review
The Hedgehog Signaling Pathway
Hedgehog–GLI (HH) signaling plays an essential role in embryogenesis and tissue homeostasis. Aberrant activation of the pathway through mutations or other mechanisms is involved in the development and progression of numerous types of cancer, including basal cell carcinoma, medulloblastoma, melanoma, breast, prostate, hepatocellular and pancreatic carcinomas. Activation of HH signaling sustains proliferation, suppresses cell death signals, enhances invasion and metastasis, deregulates cellular metabolism and promotes angiogenesis and tumor inflammation. Targeted inhibition of the HH pathway has therefore emerged as an attractive therapeutic strategy for the treatment of a wide range of cancers.
  • 726
  • 18 Jan 2023
Topic Review
The H+ Transporter SLC4A11
Solute-linked cotransporter, SLC4A11, a member of the bicarbonate transporter family, is an electrogenic H+ transporter activated by NH3 and alkaline pH. Although SLC4A11 does not transport bicarbonate, it shares many properties with other members of the SLC4 family. SLC4A11 mutations can lead to corneal endothelial dystrophy and hearing deficits that are recapitulated in SLC4A11 knock-out mice. SLC4A11, at the inner mitochondrial membrane, facilitates glutamine catabolism and suppresses the production of mitochondrial superoxide by providing ammonia-sensitive H+ uncoupling that reduces glutamine-driven mitochondrial membrane potential hyperpolarization. Mitochondrial oxidative stress in SLC4A11 KO also triggers dysfunctional autophagy and lysosomes, as well as ER stress. SLC4A11 expression is induced by oxidative stress through the transcription factor NRF2, the master regulator of antioxidant genes.
  • 447
  • 25 Jan 2022
Topic Review
The Gut–Brain Axis
The gut–brain axis (GBA) it is a complex network in which the CNS and the enteric nervous system (ENS) interact with each other in a bilateral manner by several mechanisms, including nervous, hormonal, metabolic, and immunological ones. Recently, this relationship has been described as the ‘microbiota–gut–brain axis’ because of the known role of the gut microbiota in maintaining a physiological brain–gut relationship and its participation in the pathogenesis of several diseases. In this complex network, a plethora of interactions take place.
  • 779
  • 15 Sep 2021
Topic Review
The Guanyl Radical
Guanyl radical or neutral guanine radical G(-H)• results from the loss of a H-atom or an electron/proton (e–/H+) couple from the guanine structures (G). Guanyl radical G(-H)• exists in two tautomeric forms and its role in single- and double-stranded oligonucleotides, in DNA and G-quadruplex, attracted considerable attention since directly connected to the damage of genetic material and its biological consequences. The emerging picture is still incomplete and extrapolation of its chemistry from nucleosides to more complex environment like DNA can be misleading.
  • 663
  • 20 Jul 2021
Topic Review
The Golgi Associated Retrograde Protein Complex
The Golgi associated retrograde protein complex (GARP) is an evolutionarily conserved component of Golgi membrane trafficking machinery that belongs to the Complexes Associated with Tethering Containing Helical Rods (CATCHR) family.
  • 599
  • 31 Mar 2023
Topic Review
The Glyoxalase System
The glyoxalase system was discovered over a hundred years ago and since then it has been claimed to provide the role of an indispensable enzyme system in order to protect cells from a toxic byproduct of glycolysis.
  • 1.2K
  • 27 Jan 2021
Topic Review
The Functions of NRF2 in Carcinogenesis and Cancer
The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2)-KEAP1 system is the master regulator of cellular redox and metabolic homeostasis. NRF2 has Janus-like roles in carcinogenesis and cancer development. Short-term NRF2 activation suppresses tissue injury, inflammation, and cancer initiation.
  • 222
  • 19 May 2023
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