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Karlsson Lindsay posted an update 6 months ago
Several strategies, including chemotherapy and radiotherapy, have improved therapeutic outcomes among cancer patients in clinical practice. However, due to their heterogeneity, cancer cells frequently display primary or acquired therapeutic resistance, thereby resulting in treatment failure. The mechanisms underlying cancer therapeutic resistance are complex and varied. Among them, N6-methyladenosine (m6A) RNA modification has gained increasing attention as a potential determinant of therapy resistance within various cancers. In this review, we primarily describe evidence for the effect of the m6A epitranscriptome on RNA homeostasis modulation, which has been shown to alter multiple cellular pathways in cancer research and treatment. Additionally, we discuss the profiles and biological implications of m6A RNA methylation, which is undergoing intensive investigation for its effect on the control of therapeutic resistance.
Acute myocardial infarction (AMI) initiates pathological inflammation which aggravates tissue damage and causes heart failure. Lysophosphatidic acid (LPA), produced by autotaxin (ATX), promotes inflammation and the development of atherosclerosis. The role of ATX/LPA signaling nexus in cardiac inflammation and resulting adverse cardiac remodeling is poorly understood.
We assessed autotaxin activity and LPA levels in relation to cardiac and systemic inflammation in AMI patients and C57BL/6 (WT) mice. Human and murine peripheral blood and cardiac tissue samples showed elevated levels of ATX activity, LPA, and inflammatory cells following AMI and there was strong correlation between LPA levels and circulating inflammatory cells. In a gain of function model, lipid phosphate phosphatase-3 (LPP3) specific inducible knock out (Mx1-Plpp3
) showed higher systemic and cardiac inflammation after AMI compared to littermate controls (Mx1-Plpp3
); and a corresponding increase in bone marrow progenitor cell count and proliferation. Moreover, in Mx1- Plpp3
mice, cardiac functional recovery was reduced with corresponding increases in adverse cardiac remodeling and scar size (as assessed by echocardiography and Masson’s Trichrome staining). To examine the effect of ATX/LPA nexus inhibition, we treated WT mice with the specific pharmacological inhibitor, PF8380, twice a day for 7days post AMI. Inhibition of the ATX/LPA signaling nexus resulted in significant reduction in post-AMI inflammatory response, leading to favorable cardiac functional recovery, reduced scar size and enhanced angiogenesis.
ATX/LPA signaling nexus plays an important role in modulating inflammation after AMI and targeting this mechanism represents a novel therapeutic target for patients presenting with acute myocardial injury.
ATX/LPA signaling nexus plays an important role in modulating inflammation after AMI and targeting this mechanism represents a novel therapeutic target for patients presenting with acute myocardial injury.
Sulforaphene (SFE), a naturally occurring isothiocyanate found in cruciferous vegetables, has attracted increasing attention for its anti-cancer effect in many cancers.
We explored the therapeutic effects of SFE in modulating the progression of osteosarcoma. CCK8 assay, colony formation assay, western blot, wounding healing assay and transwell assay were conducted to detect the proliferation, apoptosis, migration and invasion of osteosarcoma cells (U2OS and Saos2) treated with different concentrations of SFE. In addition, tumor xenograft in nude mice is performed to test the effects of SFE in tumorigenesis in vivo. Moreover, the levels of FSTL1 and NF-κB were determined by western blot, and loss of functions of FATL1 and NF-κB were further conducted to evaluate the underlying mechanisms of SFE on osteosarcoma development.
The results revealed that SFE inhibited the growth while promoted apoptosis of U2OS and Saos2 cells in a dose-dependent manner. Mechanistically, SFE significantly inhibited the expression of NF-κB and FSTL1. However, the genetic intervention of FSTL1 or pharmacologically inhibiting NF-κB weakened the anti-tumor role of SFE.
This study suggested that SFE alleviates the progression of osteosarcoma through modulating the FSTL1/NF-κB pathway.
This study suggested that SFE alleviates the progression of osteosarcoma through modulating the FSTL1/NF-κB pathway.Nonalcoholic fatty liver disease (NAFLD) is one of the major metabolic diseases that occur in almost one in every four global population, while colorectal cancer (CRC) is one of the leading causes of cancer related deaths in the world. Individuals with pre-existing NAFLD show a higher rate of developing CRC and liver metastasis, suggesting a causal relationship. Interestingly, both of these diseases are strongly associated with obesity, which is also a growing global health concern. In this current review, we will explore scientific findings that demonstrate the relationship between NAFLD, CRC and obesity, as well as the underlying mechanisms. We will also indicate the missing links and knowledge gaps that require more in-depth investigation.The spontaneous activity of the sinoatrial node initiates the heartbeat. Sino-atrial node dysfunction (SND) and sick sinoatrial (sick sinus) syndrome are caused by the heart’s inability to generate a normal sinoatrial node action potential. In clinical practice, SND is generally considered an age-related pathology, secondary to degenerative fibrosis of the heart pacemaker tissue. However, other forms of SND exist, including idiopathic primary SND, which is genetic, and forms that are secondary to cardiovascular or systemic disease. selleck chemical The incidence of SND in the general population is expected to increase over the next half century, boosting the need to implant electronic pacemakers. During the last two decades, our knowledge of sino-atrial node physiology and of the pathophysiological mechanisms underlying SND has advanced considerably. This review summarizes the current knowledge about SND mechanisms and discusses the possibility of introducing new pharmacologic therapies for treating SND.The poor prognosis of late gastric carcinomas (GC) underscores the necessity to identify novel biomarkers for earlier diagnosis and effective therapeutic targets. MiRNA-324-5p has been shown to be over-expressed in GC, however the biological function of miRNA-324-5p implicated in gastric cancer and its downstream targets were not well understood. Wnt/β-catenin signaling pathway is aberrantly regulated in GC. We sought to explore if miRNA-324-5p promotes oncogenesis through modulating Wnt signaling and EMT. MiRNA-324-5p is highly expressed in GC based on qRT-PCR and TCGA data. In addition, in vitro cell proliferation, cell migration assays and in vivo animal exenograft were executed to show that miRNA-324-5p is an oncogenic miRNA in GC. MiRNA-324-5p activates Wnt signaling and induces EMT in GC. Further, SUFU was identified as a target of miRNA-324-5p confirmed by western blotting and luciferase assays. Spearson analysis and TCGA data indicate that the expression of SUFU is negatively associated with the expression of miRNA-324-5p.