Acute inflammatory lesions of the placenta consist of diffuse infiltration of neutrophils at different sites in the organ. These lesions include acute chorioamnionitis, funisitis, and chorionic ...vasculitis and represent a host response (maternal or fetal) to a chemotactic gradient in the amniotic cavity. While acute chorioamnionitis is evidence of a maternal host response, funisitis and chorionic vasculitis represent fetal inflammatory responses. Intraamniotic infection generally has been considered to be the cause of acute chorioamnionitis and funisitis; however, recent evidence indicates that “sterile” intraamniotic inflammation, which occurs in the absence of demonstrable microorganisms induced by “danger signals,” is frequently associated with these lesions. In the context of intraamniotic infection, chemokines (such as interleukin-8 and granulocyte chemotactic protein) establish a gradient that favors the migration of neutrophils from the maternal or fetal circulation into the chorioamniotic membranes or umbilical cord, respectively. Danger signals that are released during the course of cellular stress or cell death can also induce the release of neutrophil chemokines. The prevalence of chorioamnionitis is a function of gestational age at birth, and present in 3–5% of term placentas and in 94% of pacentas delivered at 21-24 weeks of gestation. The frequency is higher in patients with spontaneous labor, preterm labor, clinical chorioamnionitis (preterm or term), or ruptured membranes. Funisitis and chorionic vasculitis are the hallmarks of the fetal inflammatory response syndrome, a condition characterized by an elevation in the fetal plasma concentration of interleukin-6, and associated with the impending onset of preterm labor, a higher rate of neonatal morbidity (after adjustment for gestational age), and multiorgan fetal involvement. This syndrome is the counterpart of the systemic inflammatory response syndrome in adults: a risk factor for short- and long-term complications (ie, sterile inflammation in fetuses, neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided.
Available targeted therapies for esophageal squamous cell carcinoma (ESCC) are limited; thus, further genetic and epigenetic studies are needed. Recently, many long noncoding RNAs (lncRNAs) have been ...reported to be involved in various cancers. Here, we investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC based on previous studies in lung cancer. LUCAT1 was significantly upregulated in ESCC cell lines and cancer tissue compared with normal cells and adjacent normal tissues. LUCAT1 knockdown reduced cell proliferation, induced apoptosis, and upregulated tumor-suppressor genes by reducing DNA methylation in KYSE-30 cells. Moreover, LUCAT1 siRNA reduced DNA methyltransferase 1 (DNMT1) protein levels without affecting transcription. Patients with high LUCAT1 expression had significantly lower survival rates than patients with low LUCAT1 expression. Our results thus suggest that LUCAT1 regulates the stability of DNMT1 and inhibits the expression of tumor suppressors through DNA methylation, leading to the formation and metastasis of ESCC. We identified LUCAT1 as a potential target for drug development and as a biomarker for ESCC.
•We investigated whether the lncRNA LUCAT1 was related to the carcinogenesis of ESCC.•LUCAT1 was significantly upregulated in ESCC cell lines and tissues.•LUCAT1 modulated cell proliferation, apoptosis, and tumor-suppressor genes in ESCC.•LUCAT1 regulated the stability of DNMT1.•We identified LUCAT1 as a potential drug target and biomarker for ESCC.
The advent of high-throughput RNA sequencing (RNA-seq) has led to the discovery of unprecedentedly immense transcriptomes encoded by eukaryotic genomes. However, the transcriptome maps are still ...incomplete partly because they were mostly reconstructed based on RNA-seq reads that lack their orientations (known as unstranded reads) and certain boundary information. Methods to expand the usability of unstranded RNA-seq data by predetermining the orientation of the reads and precisely determining the boundaries of assembled transcripts could significantly benefit the quality of the resulting transcriptome maps. Here, we present a high-performing transcriptome assembly pipeline, called CAFE, that significantly improves the original assemblies, respectively assembled with stranded and/or unstranded RNA-seq data, by orienting unstranded reads using the maximum likelihood estimation and by integrating information about transcription start sites and cleavage and polyadenylation sites. Applying large-scale transcriptomic data comprising 230 billion RNA-seq reads from the ENCODE, Human BodyMap 2.0, The Cancer Genome Atlas, and GTEx projects, CAFE enabled us to predict the directions of about 220 billion unstranded reads, which led to the construction of more accurate transcriptome maps, comparable to the manually curated map, and a comprehensive lncRNA catalog that includes thousands of novel lncRNAs. Our pipeline should not only help to build comprehensive, precise transcriptome maps from complex genomes but also to expand the universe of noncoding genomes.
To perform a systematic review and meta-analysis of the diagnostic performance of computed tomography (CT) and magnetic resonance (MR) imaging as noninvasive modalities for evaluating hepatocellular ...carcinoma (HCC) in patients with chronic liver disease.
A search of the MEDLINE, EMBASE, and Cochrane Library databases was performed to identify studies providing per-patient or per-lesion diagnostic accuracies of multidetector CT and MR imaging for HCCs in patients with chronic liver disease. Studies published from January 2000 to December 2012 that used a reference standard based on histopathologic findings and/or findings at follow-up were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model with further exploration with meta-regression and subgroup analyses.
Forty studies (six on multidetector CT, 22 on MR imaging, and 12 on both CT and MR imaging) were included. The studies evaluated a total of 1135 patients with multidetector CT and 2489 patients with MR imaging. The overall per-patient sensitivity of MR imaging was 88% (95% confidence interval CI: 83%, 92%), with a specificity of 94% (95% CI: 85%, 98%). The overall per-lesion sensitivity of MR imaging was higher than that of multidetector CT when the paired data of the 11 available studies were pooled (80% vs 68%, P = .0023). Gadoxetic acid-enhanced MR imaging showed significantly higher per-lesion sensitivity than MR imaging performed with other contrast agents (87% vs 74%, P = .03). Per-lesion sensitivity was significantly lower for HCCs smaller than 1 cm than that for HCCs 1 cm or larger (P < .001 for CT, P = .02 for MR imaging) and for those in explanted livers (P = .04 for CT, P < .001 for MR imaging).
MR imaging showed higher per-lesion sensitivity than multidetector CT and should be the preferred imaging modality for the diagnosis of HCCs in patients with chronic liver disease.
Wnt signaling through both canonical and noncanonical pathways plays a core role in development. Dysregulation of these pathways often causes cancer development and progression. Although the pathways ...independently contribute to the core processes, a regulatory molecule that commonly activates both of them has not yet been reported. Here, we describe a long noncoding RNA (lncRNA), HERES, that epigenetically regulates both canonical and noncanonical Wnt signaling pathways in esophageal squamous cell carcinoma (ESCC). For this study, we performed RNA-seq analysis on Korean ESCC patients and validated these results on a larger ESCC cohort to identify lncRNAs commonly dysregulated in ESCCs. Six of the dysregulated lncRNAs were significantly associated with the clinical outcomes of ESCC patients and defined 4 ESCC subclasses with different prognoses. HERES reduction repressed cell proliferation, migration, invasion, and colony formation in ESCC cell lines and tumor growth in xenograft models. HERES appears to be a transacting factor that regulates CACNA2D3, SFRP2, and CXXC4 simultaneously to activate Wnt signaling pathways through an interaction with EZH2 via its G-quadruple structure-like motif. Our results suggest that HERES holds substantial potential as a therapeutic target for ESCC and probably other cancers caused by defects in Wnt signaling pathways.
Metformin is everywhere. Originally introduced in clinical practice as an antidiabetic agent, its role as a therapeutic agent is expanding to include treatment of prediabetes mellitus, gestational ...diabetes mellitus, and polycystic ovarian disease; more recently, experimental studies and observations in randomized clinical trials suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes mellitus and reviews the results of metaanalyses of metformin in gestational diabetes mellitus as well as the treatment of obese, non-diabetic, pregnant women to prevent macrosomia. We highlight the results of a randomized clinical trial in which metformin administration in early pregnancy did not reduce the frequency of large-for-gestational-age infants (the primary endpoint) but did decrease the frequency of preeclampsia (a secondary endpoint). The mechanisms by which metformin may prevent preeclampsia include a reduction in the production of antiangiogenic factors (soluble vascular endothelial growth factor receptor-1 and soluble endoglin) and the improvement of endothelial dysfunction, probably through an effect on the mitochondria. Another potential mechanism whereby metformin may play a role in the prevention of preeclampsia is its ability to modify cellular homeostasis and energy disposition, mediated by rapamycin, a mechanistic target. Metformin has a molecular weight of 129 Daltons and therefore readily crosses the placenta. There is considerable evidence to suggest that this agent is safe during pregnancy. New literature on the role of metformin as a chemotherapeutic adjuvant in the prevention of cancer and in prolonging life and protecting against aging is reviewed briefly. Herein, we discuss the mechanisms of action and potential benefits of metformin.
Plastic pollution is becoming a significant problem in urban areas due to excessive use and careless disposal. While studies on microplastics are increasingly being conducted across various ...environments, research on microplastics in soil is limited compared to other areas. Microplastics entering the soil through various routes can stay there for a long period of time, threatening soil organisms and eventually humans. Therefore, this study was carried out to investigate the distribution characteristics of microplastics according to types of land use. For this purpose, a total of 54 soil samples were collected from agricultural land, residential areas, roadsides, parks, and forests. The analysis of microplastics in the soil by stereo microscopy showed that the average numbers of microplastics (particles/kg) in agricultural land, residential areas, roadsides, parks, and forests were 5047, 3646, 4987, 2673, and 1097, respectively. Various colors (black, red, green, blue, yellow, white, and transparent) and shapes (fragment, fiber, film, and sphere) of microplastics were found in soils. The combination of black x fragment plastics showed the highest frequency. Microplastics in soil samples from agricultural land, roadside, and residential areas with sizes between 20 µm and 500 µm were determined using Fourier transform infrared spectrometer (FT-IR) and analyzed by MP finder. The number of microplastics detected in the soil with sizes ranging between 20 µm and 500 µm was in the order of roadside > residential areas > agricultural land, which was different from the results by stereomicroscopy. Polyethylene (PE), polypropylene (PP), and polymethyl methacrylate (PMMA) were detected in soils from roadsides. Polyurethane (PU), cellulose acetate (CA), polyethylene terephthalate (PET), PP, and polystyrene (PS) were detected in soils from residential areas, with PU being the most frequently detected.
Objectives
The Korean Medication Algorithm Project for Bipolar Disorder (KMAP‐BP) is based on expert consensus and has been revised five times since 2002. This study evaluated the changes in ...treatment strategies advocated by the KMAP‐BP over time.
Methods
The five editions of the KMAP‐BP were reviewed, and the recommendations of the KMAP‐BP were compared with those of other bipolar disorder (BP) treatment guidelines.
Results
The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP). Either MS or AAP monotherapy was also considered a first‐line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. In general, although lithium and valproic acid were commonly recommended, valproic acid has been increasingly preferred for all phases of BP. The most notable changes over time included the increasing preference for AAPs for all phases of BP, and lamotrigine for the depressive and maintenance phases. The use of antidepressants for BP has gradually decreased, but still represents a first‐line option for severe and psychotic depression.
Conclusions
In general, the recommended strategies of the KMAP‐BP were similar to those of other guidelines, but differed in terms of the emphasis on rapid effectiveness, which is often desirable in actual clinical situations. The major limitation of the KMAP‐BP is that it is a consensus‐based rather than an evidence‐based tool. Nevertheless, it may confer advantages in actual clinical practice.
The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term “Fetal ...Inflammatory Response Syndrome” (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur (“rescued by birth”). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.
This paper proposes an architecture and system modules for a big data analytics platform to implement smart factories in small and medium-sized enterprises. The big data analytics platform enables ...small and medium-sized enterprises 1) to achieve the integrated system environment between the legacy system and the platform; 2) to address quality issues by applying analytical models to their factories; and 3) to reduce their financial burdens of infrastructure and experts for the platform through cloud computing. In terms of evaluation, the proposed platform was applied to the factory of a die casting company in South Korea. Using the big data analytics platform that was developed, this paper also introduced the application scenario to identify defects in the die casting process. From this empirical research, we have clarified the difficulties and challenges in applying big data analytics to small and medium-sized manufacturing enterprises. For future works, this paper suggests a manufacturing data analytics library to provide consolidated information, including a data-mining model, its datasets, and preprocessing methods for specific manufacturing problems.
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