NaNog: A pluripotency homeobox (master) molecule.

One of the most intriguing aspects of cell biology is the state of pluripotency, where the cell is capable of self-renewal for as many times as deemed necessary , then at a specified time can differentiate into any type of cell. This fundamental process is required during organogenesis in foetal life and importantly during tissue repair in health and disease. Pluripotency is very tightly regulated, as any dysregulation can result in congenital defects, inability to repair damage, or cancer. Fuelled by the relatively recent interest in stem cell biology and tissue regeneration, the molecules implicated in regulating pluripotency have been the subject of extensive research. One of the important molecules involved in pluripotency, is NaNog, the subject of this article

Global Chronic Total Occlusion Crossing Algorithm

The authors developed a global chronic total occlusion crossing algorithm following 10 steps: 1) dual angiography; 2) careful angiographic review focusing on proximal cap morphology, occlusion segment, distal vessel quality, and collateral circulation; 3) approaching proximal cap ambiguity using intravascular ultrasound, retrograde, and move-the-cap techniques; 4) approaching poor distal vessel quality using the retrograde approach and bifurcation at the distal cap by use of a dual-lumen catheter and intravascular ultrasound; 5) feasibility of retrograde crossing through grafts and septal and epicardial collateral vessels; 6) antegrade wiring strategies; 7) retrograde approach; 8) changing strategy when failing to achieve progress; 9) considering performing an investment procedure if crossing attempts fail; and 10) stopping when reaching high radiation or contrast dose or in case of long procedural time, occurrence of a serious complication, operator and patient fatigue, or lack of expertise or equipment. This algorithm can improve outcomes and expand discussion, research, and collaboration.info:eu-repo/semantics/publishedVersio

FSP1 is a glutathione-independent ferroptosis suppressor

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids1,2. To date, ferroptosis has been believed to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4)3,4 and radical-trapping antioxidants5,6. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis7 is critical to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer. Although metabolic constraints8 and phospholipid composition9,10 contribute to ferroptosis sensitivity, no cell-autonomous mechanisms have been identified that account for the resistance of cells to ferroptosis. Here we used an expression cloning approach to identify genes in human cancer cells that are able to complement the loss of GPX4. We found that the flavoprotein apoptosis-inducing factor mitochondria-associated 2 (AIFM2) is a previously unrecognized anti-ferroptotic gene. AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was initially described as a pro-apoptotic gene11, confers protection against ferroptosis elicited by GPX4 deletion. We further demonstrate that the suppression of ferroptosis by FSP1 is mediated by ubiquinone (also known as coenzyme Q10 (CoQ10)): the reduced form, ubiquinol, traps lipid peroxyl radicals that mediate lipid peroxidation, whereas FSP1 catalyses the regeneration of CoQ10 using NAD(P)H. Pharmacological targeting of FSP1 strongly synergizes with GPX4 inhibitors to trigger ferroptosis in a number of cancer entities. In conclusion, the FSP1–CoQ10–NAD(P)H pathway exists as a stand-alone parallel system, which co-operates with GPX4 and glutathione to suppress phospholipid peroxidation and ferroptosis

Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention.

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI.  1. Ischemic symptom improvement is the primary indication for CTO-PCI.  2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI.  3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges.  4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs.  5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use.  6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation.  7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training

Analysis of HCM in an understudied population reveals a new mechanism of pathogenicity

Hypertrophic Cardiomyopathy (HCM) is an inherited disease characterized by genetic and phenotypic heterogeneity. MYH7 represents one of the main sarcomere-encoding genes associated with HCM. Missense variants in this gene cause HCM through gain-of-function actions, whereby variants produce an abnormal activated protein which incorporates into the sarcomere as a "poison peptide". Here we report a frameshift variant in MYH7, c.5769delG, that is associated with HCM in an Egyptian cohort (3.3%) compared with ethnically-matched controls. This variant is absent from previously published large-scale Caucasian HCM cohorts. We further demonstrate strong evidence of co-segregation of c.5769delG with HCM in a large family (LOD score: 3.01). The predicted sequence of the variant MYH7 transcript shows that the frameshift results in a premature termination codon (PTC) downstream of the last exon-exon junction of the gene that is expected to escape nonsense-mediated decay (NMD). RNA sequencing of myocardial tissue obtained from a patient with the variant during surgical myectomy confirmed the expression of the variant MYH7 transcript. Our analysis reveals a new mechanism of pathogenicity in the understudied Egyptian population whereby distal PTC in MYH7 may lead to the expression of an abnormal protein