Recent studies have described the important multiple roles of long non‐coding RNAs (lncRNAs) during oncogenic transformation. Because the coding genome accounts for a small amount of total DNA, and ...many mutations leading to cancer occur in the non‐coding genome, it is plausible that the dysregulation of such non‐coding transcribes might also affect tumor phenotypes. Indeed, to date, lncRNAs have been reported to affect diverse biological processes through the regulation of mRNA stability, RNA splicing, chromatin structure, and miRNA‐mediated gene regulation by acting as miRNA sponges. Furthermore, accumulating studies have described the roles of lncRNAs in tumorigenesis; however, the precise mechanisms of many lncRNAs are still under investigation. Here, we discuss recently reported mechanistic insights into how lncRNAs regulate gene expression and contribute to tumorigenesis through interactions with other regulatory molecules. We especially highlight the role of taurine upregulated gene 1, which was recently reported to have biological functions related to gene regulation, and discuss the future clinical implications of lncRNAs in cancer treatments.
Understanding how lncRNAs and epigenetic regulators communicate with each other and affect gene expression is important and challenging issue to yield better options for cancer treatments. Here, we describe recently reported mechanistic insights into how lncRNAs regulate gene expression and contribute to tumorigenesis via interactions with other regulatory molecules. We also discuss the future clinical implications of lncRNAs in cancer treatments.
DNA methylation, histone modifications, and the chromatin structure are profoundly altered in human cancers. The silencing of cancer-related genes by these epigenetic regulators is recognized as a ...key mechanism in tumor formation. Recent findings revealed that DNA methylation and histone modifications appear to be linked to each other. However, it is not clearly understood how the formation of histone modifications may affect DNA methylation and which genes are relevantly involved with tumor formation. The presence of histone modifications does not always link to DNA methylation in human cancers, which suggests that another factor is required to connect these two epigenetic mechanisms. In this review, examples of studies that demonstrated the relationship between histone modifications and DNA methylation in human cancers are presented and the potential implications of these epigenetic mechanisms in human neoplasia are discussed.
The study by Filipczak and colleagues identified the interplay between mutant p53 proteins and methylcytosine dioxygenase ten-eleven translocation 1 (TET1) in lung cancers. p53 transversion mutations ...were closely associated with high TET1 expression, which prevented genomic instability-associated cellular senescence. Depletion of TET1 was synergistic with classical antitumor drugs, such as cisplatin or doxorubicin, providing an attractive rationale for targeted therapies against TET1 combined with antitumor drugs in patients with p53-mutant lung cancer.
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It is widely accepted that epigenetic alterations are associated with different stages of tumour formation and progression in many cancers. Therefore, epigenetic abnormalities in cancers are emerging ...as important biomarkers and may have therapeutic potential. The polycomb repressive complex 2 (PRC2) is a key epigenetic regulator that catalyses trimethylation of lysine 27 on histone H3 (H3K27me3) via the histone methyltransferase, EZH2, which confers stemness and regulates differentiation during embryonic development. Given these roles of EZH2 and H3K27me3, plastic and dynamic features of cancer cells, especially cancer stem cells (CSCs), may be closely associated with this epigenetic mechanism. In addition, recent sequencing technology revealed that there are many recurrent mutations in polycomb-related genes, including EZH2, in different types of cancers. Therefore, researchers focused on targeting EZH2 as a novel cancer treatment and identified small compounds that inhibit EZH2 activity. Some of them are now under clinical trial in B-cell lymphoma. However, the underlying mechanisms by which PRC2 precisely regulate epigenetic alterations at certain genomic loci under different cellular conditions remain unclear. In this review, I focus on the recent advancements in EZH2 research, especially its dynamic regulation of epigenetic alterations in tumour cells, including the CSC population, and discuss perspectives and challenges for cancer treatment in the near future.
We used a single-particle soot photometer (SP2) to measure the mass of individual black carbon (BC) particles down to ∼ 0.5 fg by means of laser-induced incandescence with an intra-cavity, ...continuous-wave laser. The incandescence of nine different types of BC samples was investigated to provide a physical basis for choosing appropriate BC materials for SP2 calibration. We estimated the vaporization temperatures of these BC samples from the spectral dependence of incandescence at the limit of the small size parameter x, for which spectral dependence of emissivity is known a priori. The vaporization temperatures differed by less than 2.2% among the samples. For the x < 1 regime of particle size, the peak amplitude of the incandescence signal measured by the SP2 was linearly proportional to the particle mass. The slopes of such linear proportionality were positively correlated with | (m
2
-1)/(m
2
+2)|, where the m is the complex refractive index of the BC particle. For particles in which x > 1, the rate of increase in the peak amplitude of the incandescence signal with increasing particle mass was negatively correlated with the compactness of particle shape, consistent with the theoretical prediction of emissivity, which accounts for particle shape. The incandescence-BC mass relationships were similar between fullerene soot and ambient soot sampled in Tokyo, thus suggesting that fullerene soot is a suitable calibration standard for SP2 measurements of ambient soot.
Early and accurate diagnosis of sepsis is challenging. Although procalcitonin and presepsin have been identified as potential biomarkers to differentiate between sepsis and other non-infectious ...causes of systemic inflammation, the diagnostic accuracy of these biomarkers remains controversial. Herein, we performed a comprehensive meta-analysis to assess the overall diagnostic value of procalcitonin and presepsin for the diagnosis of sepsis.
We searched three electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials) for relevant studies. Two authors independently screened articles on the basis of inclusion and exclusion criteria. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. The quality of evidence for diagnostic accuracy in absolute effects, i.e., the number of true or false positives and true or false negatives, gave a particular pre-test probability.
We included 19 studies (19 observational studies and no randomized controlled trials) that had enrolled 3012 patients. Analyses of summary receiver operating characteristic curves revealed areas under the receiver operating characteristic curves of 0.84 for procalcitonin and 0.87 for presepsin. The pooled sensitivities and specificities were 0.80 (95% confidence interval 0.75 to 0.84) and 0.75 (95% confidence interval 0.67 to 0.81) for procalcitonin. For presepsin, these values were 0.84 (95% confidence interval 0.80 to 0.88) and 0.73 (95% confidence interval 0.61 to 0.82), respectively. There were no statistically significant differences in both pooled sensitivities (
= 0.48) and specificities (
= 0.57) between procalcitonin and presepsin.
Our meta-analysis provided evidence that the diagnostic accuracy of procalcitonin and presepsin in detecting infection was similar and that both are useful for early diagnosis of sepsis and subsequent reduction of mortality in critically ill adult patients.
The study was registered in PROSPERO under the registration number CRD42016035784.
Recent studies provide compelling evidence that epigenetic dysregulation is involved in almost every step of tumor development and progression. Differences in tumor behavior, which ultimately ...reflects clinical outcome, can be explained by variations in gene expression patterns generated by epigenetic mechanisms, such as DNA methylation. Therefore, epigenetic abnormalities are considered potential biomarkers and therapeutic targets. DNA methylation is stable at certain specific loci in cancer cells and predominantly reflects the characteristic clinicopathological features. Thus, it is an ideal biomarker for cancer screening, classification and prognostic purposes. Epigenetic treatment for cancers is based on the pharmacologic targeting of various core transcriptional programs that sustains cancer cell identity. Therefore, targeting aberrant epigenetic modifiers may be effective for multiple processes compared with using a selective inhibitor of aberrant single signaling pathway. This review provides an overview of the epigenetic alterations in human cancers and discusses about novel therapeutic strategies targeting epigenetic alterations.
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Heat stroke Hifumi, Toru; Kondo, Yutaka; Shimizu, Keiki ...
Journal of intensive care,
05/2018, Volume:
6, Issue:
1
Journal Article
Peer reviewed
Open access
Heat stroke is a life-threatening injury requiring neurocritical care; however, heat stroke has not been completely examined due to several possible reasons, such as no universally accepted ...definition or classification, and the occurrence of heat wave victims every few years. Thus, in this review, we elucidate the definition/classification, pathophysiology, and prognostic factors related to heat stroke and also summarize the results of current studies regarding the management of heat stroke, including the use of intravascular balloon catheter system, blood purification therapy, continuous electroencephalogram monitoring, and anticoagulation therapy.
Two systems for the definition/classification of heat stroke are available, namely Bouchama's definition and the Japanese Association for Acute Medicine criteria. According to the detailed analysis of risk factors, prevention strategies for heat stroke, such as air conditioner use, are important. Moreover, hematological, cardiovascular, neurological, and renal dysfunctions on admission are associated with high mortality, which thus represent the potential targets for intensive and specific therapies for patients with heat stroke. No prospective, comparable study has confirmed the efficacy of intravascular cooling devices, anticoagulation, or blood purification in heat stroke.
The effectiveness of cooling devices, drugs, and therapies in heat stroke remains inconclusive. Further large studies are required to continue to evaluate these treatment strategies.
Sepsis-associated muscle wasting (SAMW) is characterized by decreased muscle mass, reduced muscle fiber size, and decreased muscle strength, resulting in persistent physical disability accompanied by ...sepsis. Systemic inflammatory cytokines are the main cause of SAMW, which occurs in 40-70% of patients with sepsis. The pathways associated with the ubiquitin-proteasome and autophagy systems are particularly activated in the muscle tissues during sepsis and may lead to muscle wasting. Additionally, expression of muscle atrophy-related genes Atrogin-1 and MuRF-1 are seemingly increased via the ubiquitin-proteasome pathway. In clinical settings, electrical muscular stimulation, physiotherapy, early mobilization, and nutritional support are used for patients with sepsis to prevent or treat SAMW. However, there are no pharmacological treatments for SAMW, and the underlying mechanisms are still unknown. Therefore, research is urgently required in this field.
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