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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. 
  • 554
  • 30 Mar 2021
Topic Review
Autophagy in Human Diseases
Autophagy, a process of cellular self-digestion, delivers intracellular components including superfluous and dysfunctional proteins and organelles to the lysosome for degradation and recycling and is important to maintain cellular homeostasis. In recent decades, autophagy has been found to help fight against a variety of human diseases, but, at the same time, autophagy can also promote the procession of certain pathologies, which makes the connection between autophagy and diseases complex but interesting.
  • 554
  • 06 Dec 2021
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. 
  • 553
  • 07 Jul 2022
Biography
Clemente Estable
Clemente Estable (23 May 1894, Canelones – 27 October 1976, Montevideo) was a University Professor and Docent. He was a pioneer in the areas of cellular biology and neurobiology research. Estable was an educator, scientist and philosopher who left his mark on the intellectual collective thinking of his native land. He lived his life guided by strong democratic values and ethical principles and
  • 553
  • 01 Dec 2022
Topic Review
Hepatocellular Carcinoma Management's Gut Microbiota
Liver cancer, predominantly hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths worldwide. Emerging data highlight the importance of gut homeostasis in the pathogenesis of HCC. Clinical and translational studies revealed the patterns of dysbiosis in HCC patients and their potential role for HCC diagnosis. Research on underlying mechanisms of dysbiosis in HCC development pointed out the direction for improving the treatment and prevention. Despite missing clinical studies, animal models showed that modulation of the gut microbiota by probiotics may become a new way to treat or prevent HCC development. 
  • 553
  • 08 Jul 2021
Topic Review
Flipons and Condensates Enhances Evolution
A number of insights derive from viewing flipons as scaffolds for condensates. Flipons provide a controlled way to initiate condensate formation, one subject to natural selection. The alternative conformation localizes required factors needed to regulate transcription, RNA processing, and epigenetic modification, while excluding nucleosomes and other B-DNA- and A-RNA-specific proteins that produce competing outcomes.
  • 553
  • 22 Sep 2021
Topic Review
Endothelial Autophagy in Cardiovascular Disease
Autophagy is a highly conserved process in which obsolete and dysfunctional cytoplasmic components (such as unfolded proteins, lipids, and damaged organelles) are degraded and recycled, and infectious organisms are removed by lysosomes. Deficient or uncontrolled activation of endothelial autophagy is associated with the onset and development of diverse cardiovascular diseases (CVDs), including coronary microvascular dysfunction” (CMD).
  • 552
  • 07 Jul 2022
Topic Review
Chromosomal Instability
Chromosomal instability is the process of mis-segregation for ongoing chromosomes, which leads to cells with an abnormal number of chromosomes, also known as an aneuploid state. Induced aneuploidy is detrimental during development and in primary cells but aneuploidy is also a hallmark of cancer cells. It is therefore believed that premalignant cells need to overcome aneuploidy-imposed stresses to become tumorigenic. Over the past decade, some aneuploidy-tolerating pathways have been identified through small-scale screens, which suggests that aneuploidy tolerance pathways can potentially be therapeutically exploited. However, to better understand the processes that lead to aneuploidy tolerance in cancer cells, large-scale and unbiased genetic screens are needed, both in euploid and aneuploid cancer models.
  • 552
  • 23 Feb 2021
Topic Review
Read
In DNA sequencing, a read is an inferred sequence of base pairs (or base pair probabilities) corresponding to all or part of a single DNA fragment. A typical sequencing experiment involves fragmentation of the genome into millions of molecules, which are size-selected and ligated to adapters. The set of fragments is referred to as a sequencing library, which is sequenced to produce a set of reads.
  • 551
  • 24 Nov 2022
Topic Review
Fibronectin in Osteoarthritis
Fibronectin is a component of the extracellular matrix essential to its assembly, which also regulates some cellular functions. However, cleavage of fibronectin in pathological conditions releases fibronectin fragments with pro-inflammatory and degradative properties. During the development of osteoarthritis, tissue proteolysis and injury induce extracellular matrix degradation, generating fibronectin fragments that promote inflammation and degradation by the induction of cytokine and proteinase expressions.
  • 550
  • 02 Dec 2021
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