arrested development

BACKGROUND: Cardiac pacemaker implantation may be indicated in patients with refractory bradycardia following a cervical spinal cord injury (CSCI). However, evidence about the impact of this procedure on outcomes is lacking. We planned a study to assess whether the implantation of a pacemaker would decrease mortality and hospital resource utilization in patients with CSCI. METHODS: Adult patients with CSCI in the Trauma Quality Improvement Program (TQIP) database between 2016 and 2019 were retrospectively analyzed...

BACKGROUND: Oral cancer is a major public health concern worldwide, with oral squamous cell carcinoma (OSCC) being one of its most common subtypes. Despite advances in diagnosis and management of this disease, there remains a need to develop new therapeutic approaches for better outcomes. OBJECTIVE: This study aimed to investigate the molecular mechanisms through which cinnamoyl sulfonamide hydroxamate derivatives exert their anticancer effects on OSCC. MATERIALS AND METHODS: The derivatives were synthesized via multi-step processes and then characterized at the molecular level...

Senescence is a heterogenous and dynamic process in which various cell types undergo cell-cycle arrest due to cellular stressors. While senescence has been implicated in aging and many human pathologies, therapeutic interventions remain inadequate due to the absence of a comprehensive set of biomarkers in a context-dependent manner. Polyphenols have been investigated as senotherapeutics in both preclinical and clinical settings. However, their use is hindered by limited stability, toxicity, modest bioavailability, and often inadequate concentration at target sites...

IRAK1 has been implicated in promoting development of various types of cancers and mediating radioresistance. However, its role in cervical cancer tumorigenesis and radioresistance, as well as the potential underlying mechanisms, remain poorly defined. In this study, we evaluated IRAK1 expression in radiotherapy-treated cervical cancer tissues and found that IRAK1 expression is negatively associated with the efficacy of radiotherapy. Consistently, ionizing radiation (IR)-treated HeLa and SiHa cervical cancer cells express a lower level of IRAK1 than control cells...

BACKGROUND AND AIM: Cellular senescence of hepatocytes involves permanent cell cycle arrest, disrupted cellular bioenergetics, resistance to cell death, and the release of pro-inflammatory cytokines. This 'zombie-like' state perpetuates harmful effects on tissues and holds potential implications for liver disease progression. Remarkably, senescence exhibits heterogeneity, stemming from two crucial factors: the inducing stressor and the cell type. As such, our present study endeavors to characterize stressor-specific changes in senescence phenotype, its related molecular patterns, and cellular bioenergetics in primary mouse hepatocytes (PMH) and hepatocyte-derived liver organoids (HepOrgs)...

In recent years, invasive resuscitation methods utilizing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) have gained significant attention. Despite advances in traditional resuscitation measures, out-of-hospital cardiac arrest (OHCA) mortality remains high. In the context of extracorporeal cardiopulmonary resuscitation (ECPR), VA-ECMO therapy offers a promising approach by providing circulatory support during cardiac arrest, allowing time for diagnostic evaluation and targeted therapy. However, patient selection for ECPR remains a challenge, relying on various factors including initial rhythm, duration of no-flow and low-flow states, as well as presence of reversible causes...

Muscles undergo developmental transitions in gene expression and alternative splicing that are necessary to refine sarcomere structure and contractility. CUG-BP and ETR-3-like (CELF) family RNA-binding proteins are important regulators of RNA processing during myogenesis that are misregulated in diseases such as Myotonic Dystrophy Type I (DM1). Here, we report a conserved function for Bruno 1 (Bru1, Arrest), a CELF1/2 family homolog in Drosophila, during early muscle myogenesis. Loss of Bru1 in flight muscles results in disorganization of the actin cytoskeleton leading to aberrant myofiber compaction and defects in pre-myofibril formation...

Ferroptosis, an iron-triggered modality of cellular death, has been reported to closely relate to human aging progression and aging-related diseases. However, the involvement of ferroptosis in the development and maintenance of senescent cells still remains elusive. Here, we established a doxorubicin-induced senescent HSkM cell model and found that both iron accumulation and lipid peroxidation increase in senescent cells. Moreover, such iron overload in senescent cells has changed the expression panel of the ferroptosis-response proteins...

BACKGROUND: Glucocorticoids (GCs) are commonly used as the primary chemotherapy for lymphoid malignancies, including acute lymphoblastic leukemia (ALL). However, the development of GC resistance limits their prolonged use. METHODS: In this study, we investigated the potential of a newly synthesized indole derivative called LWX-473, in combination with the classic GC Dexamethasone (DEX), to enhance the responsiveness of Jurkat cells to GC treatment. RESULTS: Our findings demonstrate that LWX-473 alone or in combination with DEX significantly improves GC-induced cell apoptosis and arrests the cell cycle in the G1 phase...

Glioma, a malignant brain tumor originating from neural glial cells, presents significant treatment challenges. However, the underlying mechanisms of glioma development are not fully understood, and effective targets are lacking. This study provides insights into the role of insulin-like growth factor 2 messenger RNA-binding protein 2 (IGF2BP2) in glioma progression and its therapeutic potential. Our analysis illustrated that elevated IGF2BP2 expression associated with significantly shorter survival among patients with low-grade glioma (LGG) in The Cancer Genome Atlas (TCGA) database...

XIAP, or the X-linked Inhibitor of Apoptosis Protein, is the most extensively studied member within the IAP gene family. It possesses the capability to impede apoptosis through direct inhibition of caspase activity. Various kinds of cancers overexpress XIAP to enable cancer cells to avoid apoptosis. Consequently, the inhibition of XIAP holds significant clinical implications for the development of anti-tumor medications and the treatment of cancer. In this study, sterigmatocystin, a natural compound obtained from the genus asperigillus , was demonstrated to be able to induce apoptotic and autophagic cell death in liver cancer cells...

AIMS: Despite its implication in various human cancers, the expression and functional significance of Kinesin family member 15 (KIF15) in chordomas remain unexplored. MAIN METHODS: The evaluation of KIF15 protein levels was conducted through immunohistochemistry (IHC) staining and Western blot analysis. Cell proliferation was quantified using MTT and CCK8 assays, whereas cell migration was examined using wound healing and Transwell assays. Furthermore, flow cytometric analysis was utilized to assess cell apoptosis and the cell cycle...

Kinesin spindle protein (KSP) inhibitors are one of the most promising anticancer agents developed in recent years. Herein, we report the synthesis of ispinesib-core pyridine derivative conjugates, which are potent KSP inhibitors, with half-sandwich complexes of ruthenium, osmium, rhodium, and iridium. Conjugation of 7-chloroquinazolin-4(3H)-one with the pyridine-2-ylmethylimine group and the organometallic moiety resulted in up to a 36-fold increased cytotoxicity with IC50 values in the micromolar and nanomolar range also toward drug-resistant cells...

BACKGROUND: This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure. CASE SUMMARY: Here, we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital...

In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development...

BACKGROUND: Silver diamine fluoride (SDF) gel was developed to overcome the clinical limitations of liquids with children. The authors conducted a clinical trial to determine caries lesion arrest in primary teeth at 1-year follow-up when 38% SDF gel and 2.5% sodium fluoride varnish were applied sequentially at the same appointment. Parent satisfaction was assessed. METHODS: The study design was an open-label prospective, clinical trial with single group assignment...

The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals...

The mortality rate of newborns with severe congenital heart disease (CHD) has significantly decreased over the past few decades. However, many of these children experience neurological impairments, particularly following a hypoxic cardiac arrest. The use of extracorporeal membrane oxygenation (ECMO) has been considered an effective treatment for severe hypoxia in CHD cases. Various clinical studies have examined the use of ECMO for resuscitation after hypoxic cardiac arrest, but the results have been contradictory, showing a significant incidence of both mortality and morbidity in some studies while others report good outcome...

Myocardial ischemia-reperfusion injury (IRI) after myocardial ischemia, cardiac surgery, or circulatory arrest leads to adverse cardiovascular outcomes. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, namely, ischemia, resulting in damage or dysfunction of the cardiac tissue. Early restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome...

BACKGROUND: Mitochondrial dysfunction, which is triggered by systemic ischemia-reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury...