Elevated cholesteryl ester transfer and phospholipid transfer proteins aggravated psoriasis in imiquimod-induced mouse models.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder related to dyslipidemia, with decreased high-density lipoprotein (HDL). Various cell types express phospholipid transfer protein (PLTP) as well as cholesteryl ester transfer protein (CETP). Their elevated levels among transgenic (Tg) mice led to reduced HDL and a higher risk of atherosclerosis (AS). This study examined whether elevated CETP and PLTP could aggravate psoriasis in a psoriasis vulgaris mouse model. METHODS: The back skins of CETP-Tg, PLTP-Tg, and C57BL/6 male mice, aged six to 8 weeks, were shaved for imiquimod cream (IMQ) (5%) treatment for five consecutive days. The clinical pathological parameters were rated independently using the modified target lesion psoriasis severity score. The skin sections stained with hematoxylin-eosin were scored by the Baker score. Epidermal thickening and differentiation and inflammatory factor infiltration were determined by immunohistochemistry. Inflammatory cytokine levels were measured using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. This work employed SPSS Statistics Version to conduct statistical analyses. RESULTS: In this study, CETP-Tg and PLTP-Tg mice had higher clinical and histological scores than wild-type (WT) mice. Immunohistochemistry of the epidermis and dermis revealed a high proportion of proliferating cell nuclear antigen (PCNA) positivity within psoriatic skin lesions of CETP-Tg and PLTP-Tg mice compared with WT mice. Interferon-α (IFN-α), interleukin-1ß (IL-1ß), IL-6, IL-17A, IL-17F, IL-22, and IL-23p19 mRNA levels increased within CETP-Tg and PLTP-Tg mice compared with WT counterparts. In comparison with WT mice, plasma tumor necrosis factor-α (TNF-α) levels, rather than IL-6 levels, were increased in CETP-Tg and PLTP-Tg mice. CONCLUSIONS: Elevated CETP and PLTP aggravate psoriasis in a imiquimod-induced mouse model.

Droplet digital PCR for quantification of PML-RARα in acute promyelocytic leukemia: a comprehensive comparison with real-time PCR.

Real-time quantitative PCR (qPCR) has been widely implemented for molecular testing, but there are still some inherent limitations that hamper its usefulness. Droplet digital PCR (ddPCR), which can provide direct, standards-free quantification, has recently received increasing attention. In our study, a comprehensive comparison of ddPCR with qPCR in relation to the quantification of PML-RARα was performed to evaluate the diagnostic potential of ddPCR. Results showed that ddPCR displayed significant concordance with qPCR in the detection of PML-RARα in clinical samples, but showed advantages over qPCR in terms of precision, limit of detection (LOD), and other basic performance parameters. A study of the feasibility of duplexing also indicated that ddPCR could simultaneously quantify the target PML-RARα and the clinical common reference gene ABL in a reaction, in contrast to qPCR. Moreover, ddPCR was more tolerant than qPCR of inhibition, and was shown to be able to quantify inhibition-prone samples. Another advantage of using ddPCR in clinical applications is that it will yield accurate results for patients with PML-RARα levels that fluctuate around the LOD of qPCR. Therefore, ddPCR is considered to have the potential to become a reliable alternative technique for quantifying PML-RARα. Graphical abstract ᅟ.

The Contribution of Necroptosis in Neurodegenerative Diseases.

Over the past decades, cell apoptosis has been significantly reputed as an accidental, redundant and alternative manner of cell demise which partakes in homeostasis in the development of extensive diseases. Nevertheless, necroptosis, another novel manner of cell death through a caspase-independent way, especially in neurodegenerative diseases remains ambiguous. The cognition of this form of cell demise is helpful to understand other forms of morphological resemblance of necrosis. Additionally, the concrete signal mechanism in the regulation of necroptosis is beneficial to the diagnosis and treatment of neurodegenerative diseases. Recent studies have demonstrated that necroptotic inhibitor, 24(S)-Hydroxycholesterol and partial specific histone deacetylase inhibitors could alleviate pathogenetic conditions of neurodegenerative diseases via necroptosis pathway. In this review, we summarize recent researches about mechanisms and modulation of necroptotic signaling pathways and probe into the role of programmed necroptotic cell demise in neurodegenerative diseases such as Parkinson's disease, Multiple sclerosis, Amyotrophic lateral sclerosis.

A review of the challenge in measuring and standardizing BCR-ABL1.

Breakpoint cluster region-Abelson (BCR-ABL1) translocation is the characteristic sign of chronic myeloid leukemia (CML). The quantitation of BCR-ABL1 messenger RNA is requisite for patients with CML, and reverse-transcription real-time quantitative polymerase chain reaction (RQ-PCR) is the method used most extensively in testing laboratories worldwide. Nevertheless, substantial variation in RQ-PCR results from different laboratories makes interlaboratory comparability inconvincible owing to the lack of standardization. To facilitate interlaboratory comparative assessment and international standardization, an international scale (IS) for BCR-ABL1 was proposed. The laboratory-specific conversion factors derived from the IS can convert local different values to the IS without changing procedures. The standardization of BCR-ABL1 also includes the whole analytical process, so it is noteworthy to pay attention to the quality control before BCR-ABL1 quantitative analysis. More importantly, the World Health Organization has validated a first genetic reference panel which is limited to the manufacturers to produce and calibrate secondary reference reagents. Also, a certified reference plasmid, ERM-AD623, was internationally accepted. This article mainly focuses on BCR-ABL1 measurement and these standardization efforts in progress.

Ultrasensitive detection strategy for CAP by molecularity imprinted SERS sensor based on multiple synergistic enhancement of SiO2@AuAg with MOFs@Au signal carrier.

Chloramphenicol (CAP) residue in food can cause great harm to human health, it is important to develop a rapid and sensitive method to detect CAP. Here, molecularly imprinted polymer (MIP) was combined with metal-organic frameworks@Au (MOFs@Au) collaborative construction surface-enhanced Raman spectroscopy (SERS) based aptasensor for CAP ultrasensitive detection. MOFs@Au first carried the Raman signal molecule toluidine blue (TB) and aptamer to form MOFs@Au@TB@Apt. In addition, rMIP (CAP was removed) was dropped onto the uniform three-dimensional (3D) SERS substrate SiO2@AuAg to form SiO2@AuAg@rMIP. In the presence of target CAP, it could be specifically captured with rMIP by covalent interaction and was recognised by the aptamer. During this time, SiO2@AuAg@rMIP@CAP could selectively connect MOFs@Au@TB@Apt to realise synergistic enhance the Raman signal. Based on this principle, the proposed SERS aptasensor exhibits excellent sensitivity with a detection limit of 7.59×10-13 M for CAP, providing a new strategy for trace detection in food.

Compositional and Hollow Engineering of Silicon Carbide/Carbon Microspheres as High-Performance Microwave Absorbing Materials with Good Environmental Tolerance.

Microwave absorbing materials (MAMs) characterized by high absorption efficiency and good environmental tolerance are highly desirable in practical applications. Both silicon carbide and carbon are considered as stable MAMs under some rigorous conditions, while their composites still fail to produce satisfactory microwave absorption performance regardless of the improvements as compared with the individuals. Herein, we have successfully implemented compositional and structural engineering to fabricate hollow SiC/C microspheres with controllable composition. The simultaneous modulation on dielectric properties and impedance matching can be easily achieved as the change in the composition of these composites. The formation of hollow structure not only favors lightweight feature, but also generates considerable contribution to microwave attenuation capacity. With the synergistic effect of composition and structure, the optimized SiC/C composite exhibits excellent performance, whose the strongest reflection loss intensity and broadest effective absorption reach - 60.8 dB and 5.1 GHz, respectively, and its microwave absorption properties are actually superior to those of most SiC/C composites in previous studies. In addition, the stability tests of microwave absorption capacity after exposure to harsh conditions and Radar Cross Section simulation data demonstrate that hollow SiC/C microspheres from compositional and structural optimization have a bright prospect in practical applications.

Gestational exposure to 1-NP induces ferroptosis in placental trophoblasts via CYP1B1/ERK signaling pathway leading to fetal growth restriction.

Fetal growth restriction (FGR) is a prevalent complication in obstetrics, yet its exact aetiology remains unknown. Numerous studies suggest that the degradation of the living environment is a significant risk factor for FGR. 1-Nitropyrene (1-NP) is a widespread environmental pollutant as a representative substance of nitro-polycyclic aromatic hydrocarbons. In this study, we revealed that 1-NP induced FGR in fetal mice by constructing 1-NP exposed pregnant mice models. Intriguingly, we found that placental trophoblasts of 1-NP exposed mice exhibited significant ferroptosis, which was similarly detected in placental trophoblasts from human FGR patients. In this regard, we established a 1-NP exposed cell model in vitro using two human trophoblast cell lines, HTR8/SVneo and JEG-3. We found that 1-NP not only impaired the proliferation, migration, invasion and angiogenesis of trophoblasts, but also induced severe cellular ferroptosis. Meanwhile, the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively rescued 1-NP-induced trophoblast biological function impairment. Mechanistically, we revealed that 1-NP regulated ferroptosis by activating the ERK signaling pathway. Moreover, we innovatively revealed that CYP1B1 was essential for the activation of ERK signaling pathway induced by 1-NP. Overall, our study innovatively identified ferroptosis as a significant contributor to 1-NP induced trophoblastic functional impairment leading to FGR and clarified the specific mechanism by which 1-NP induced ferroptosis via the CYP1B1/ERK signaling pathway. Our study provided novel insights into the aetiology of FGR and revealed new mechanisms of reproductive toxicity of environmental pollutants.

A differential role of macrophage TRPM2 channels in Ca²âº signaling and cell death in early responses to H2O2.

Reactive oxygen species such as H2O2 elevates the cytosolic Ca²âº concentration ([Ca²âº]c) and causes cell death via poly(ADPR) polymerase (PARP) activation, which also represents the primary mechanism by which H2O2 activate the transient receptor potential melastatin-related 2 (TRPM2) channel as a Ca²âº-permeable channel present in the plasma membrane or an intracellular Ca²âº-release channel. The present study aimed to define the contribution and mechanisms of the TRPM2 channels in macrophage cells in mediating Ca²âº signaling and cell death during initial response to H2O2, using mouse peritoneal macrophage, RAW264.7, and differentiated THP-1 cells. H2O2 evoked robust increases in the [Ca²âº]c, and such Ca²âº responses were significantly greater at body temperature than room temperature. H2O2-induced Ca²âº responses were strongly inhibited by pretreatment with PJ-34, a PARP inhibitor, and largely prevented by removal of extracellular Ca²âº. Furthermore, H2O2-induced increases in the [Ca²âº]c were completely abolished in macrophage cells isolated from trpm2-/- mice. H2O2 reduced macrophage cell viability in a duration- and concentration-dependent manner. H2O2-induced cell death was significantly attenuated by pretreatment with PJ-34 and TRPM2 channel deficiency but remained significant and persistent. Taken together, these results show that the TRPM2 channel in macrophage cells functions as a cell surface Ca²âº-permeable channel that mediates Ca²âº influx and constitutes the principal Ca²âº signaling mechanism but has a limited, albeit significant, role in cell death during early exposure to H2O2.

Effect of mask coverage on face identification in Taiwanese men and women.

Mask wearing is the easiest and most effective way to avoid COVID-19 infection; however, it affects interpersonal activities, especially face identification. This study examined the effects of three mask coverage levels (full coverage, FC; coverage up to the middle [MB] or bottom of the nose bridge [BB]) on face identification accuracy and time. A total of 115 university students (60 men and 55 women) were recruited to conduct a computer-based simulation test consisting of 30 questions (10 questions [five face images each of men and women] for the three mask coverage levels). One unmasked target face and four face images with a specified mask coverage level were designed for each question, and the participants were requested to select the same face from the four covered face images on the basis of the target face. The ANOVA results indicated that identification accuracy was significantly affected by sex (p < 0.01) and the mask coverage level (p < 0.001), whereas identification time was only influenced by sex (p < 0.05). The multiple comparison results indicated that the identification accuracy rate for faces wearing a mask with FC (90.3%) was significantly lower than for those wearing masks with coverage up to the MB (93.7%) and BB (94.9%) positions; however, no difference in identification accuracy rate was observed between the MB and BB levels. Women exhibited a higher identification accuracy rate than men (94.1% vs. 91.9%) in identifying unfamiliar faces, even though they may spend less time identifying the images. A smaller mask coverage level (i.e., the BB level) does not facilitate face identification. The findings can be served as a reference for people to trade-off between wearing a mask and interpersonal interaction in their daily activities.

Cardiometabolic index is associated with urinary albumin excretion and renal function in aged person over 60: Data from NHANES 2011-2018.

PURPOSE: Cardiometabolic index (CMI) is recently considered to have certain significance in the screening of diabetes, atherosclerosis, and renal dysfunction. Therefore, this study intends to explore the relationship between CMI and the risk of albuminuria. METHODS: This is a cross-sectional study involving 2732 elderly people (age ≥ 60). The research data are from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Calculate CMI index: Triglyceride (TG) (mmol/L)/ High density lipid-cholesterol (HDLC) (mmol/L) × WHtR. RESULTS: The CMI level in microalbuminuria group was significantly higher than that in normal albuminuria group (P < 0.05 or P < 0.01), whether in the general population or in diabetes and hypertensive population respectively. The proportion of abnormal microalbuminuria increased gradually with the increase of CMI tertile interval (P < 0.01). Correlation analysis showed that CMI was positively correlated with urinary albumin-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine (Scr), and negatively correlated with estimated glomerular filtration rate (eGFR). With the occurrence of albuminuria as the dependent variable, weighted logistic regression analysis showed that CMI was an independent risk factor for microalbuminuria. Weighted smooth curve fitting showed that CMI index was linearly related to the risk of microalbuminuria. Subgroup analysis and interaction test showed that they participated in this positive correlation. CONCLUSIONS: Obviously, CMI is independently associated with microalbuminuria, suggesting that CMI, a simple indicator, can be used for risk assessment of microalbuminuria, especially in diabetes patients.

State-of-the-art in carbides/carbon composites for electromagnetic wave absorption.

Electromagnetic wave absorbing materials (EWAMs) have made great progress in the past decades, and are playing an increasingly important role in radiation prevention and antiradar detection due to their essential attenuation toward incident EM wave. With the flourish of nanotechnology, the design of high-performance EWAMs is not just dependent on the intrinsic characteristics of single-component medium, but pays more attention to the synergistic effects from different components to generate rich loss mechanisms. Among various candidates, carbides and carbon materials are usually labeled with the features of chemical stability, low density, tunable dielectric property, and diversified morphology/microstructure, and thus the combination of carbides and carbon materials will be a promising way to acquire new EWAMs with good practical application prospects. In this review, we introduce EM loss mechanisms related to dielectric composites, and then highlight the state-of-the-art progress in carbides/carbon composites as high-performance EWAMs, including silicon carbide/carbon, MXene/carbon, molybdenum carbide/carbon, as well as some uncommon carbides/carbon composites and multicomponent composites. The critical information regarding composition optimization, structural engineering, performance reinforcement, and structure-function relationship are discussed in detail. In addition, some challenges and perspectives for the development of carbides/carbon composites are also proposed after comparing the performance of some representative composites.

Microfluidic chemostatic bioreactor for high-throughput screening and sustainable co-harvesting of biomass and biodiesel in microalgae.

As a renewable and sustainable source for energy, environment, and biomedical applications, microalgae and microalgal biodiesel have attracted great attention. However, their applications are confined due to the cost-efficiency of microalgal mass production. One-step strategy and continuous culturing systems could be solutions. However, current studies for optimization throughout microalgae-based biofuel production pipelines are generally derived from the batch culture process. Better tools are needed to study algal growth kinetics in continuous systems. A microfluidic chemostatic bioreactor was presented here, providing low-bioadhesive cultivations for algae in a cooperative environment of gas, nutrition, and temperature (GNT) involved with high throughput. The chip was used to mimic the continuous culture environment of bioreactors. It allowed simultaneously studying of 8 × 8 different chemostatic conditions on algal growth and oil production in parallel on a 7 × 7 cm2 footprint. On-chip experiments of batch and continuous cultures of Chlorella. sp. were performed to study growth and lipid accumulation under different nitrogen concentrations. The results demonstrated that microalgal cultures can be regulated to grow and accumulate lipids concurrently, thus enhancing lipid productivity in one step. The developed on-chip culturing condition screening, which was more suitable for continuous bioreactor, was achieved at a half shorter time, 64-times higher throughput, and less reagent consumption. It could be used to establish chemostat cultures in continuous bioreactors which can dramatically accelerate the development of renewable and sustainable algal for CO2 fixation and biosynthesis and related systems for advanced sustainable energy, food, pharmacy, and agriculture with enormous social and ecological benefits.

PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis.

Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal numbers and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies.

Career Development and Occupational Disease in Chinese Nurses: A Cross-Sectional Study.

BACKGROUND: A high tendency of intention to leave has been noted for nurses in China. The nursing profession is currently unstable. METHODS: A sample of 51406 nurses from 311 hospitals in China who completed the self-administered questionnaire online was recruited via the China Nursing Association by email and phone using a simple random sampling method. The recruitment occurred between July 2016 and July 2017. RESULTS: The majority of the nurses had working experience ≤20 years and had to work on night shifts. A high percentage of nurses (71.8%) had insomnia, followed by 37.0% who developed varicose veins and 40.9% who experienced musculoskeletal-related disorders. The proportions of the nurses who developed gastrointestinal and urinary system diseases were 56.0% and 18.2%, respectively. Nearly half of the nurses did not have a clear goal for their future career development and intended to leave. Nurses with long working hours each week were positively associated with the development of occupational diseases. The prevalence of occupational diseases was independently associated with career development. CONCLUSIONS: A high prevalence of occupational diseases was noted among nurses in China. The data indicated that 50% of the nurses were vague regarding their career planning. The data suggest that managers need to pay more attention and to prevent this problem. Appropriate interventions should also be provided.

Creating a Healthy Life for the Elderly through Participation in Self-Media: A Study on the Demands of the Elderly in Self-Media.

In recent years, with the trends in digital media and a shift in the sources of information, self-media has gradually become a unique new type of media with considerable potential. Numerous related studies have also indicated that participating in self-media positively impacts the elderly, especially in self-media regarding healthcare and welfare. However, research has seldom explored the demands and services for elderly participation in self-media. In this study, the research targets were 55-75 years of age, in good health, with a monthly disposable income of more than TWD 30,000 (N = 180). The research methods had two aims: (1) to analyze the current well-known self-media and websites related to healthcare; and (2) via the Kano Model questionnaire, to survey and explore the demand for self-media among the elderly. The results summarize and describe the preferred layout, content items, interaction methods, and information display of self-media content for the elderly. We anticipate designing a self-media website platform that meets the demands of the elderly and that continues to develop into social media platforms and audio-visual content in the future.

Effectiveness of self-efficacy-enhancing interventions on rehabilitation following total hip replacement: a randomized controlled trial with six-month follow-up.

BACKGROUND: As the world's population ages, hip replacement, a routine treatment for arthritis, has become more common. However, after surgery, rehabilitation has some limited effectiveness with postoperative complications and persistent impairments. This study aimed to explore the effect of a self-efficacy-enhancing intervention program following hip replacement on patients' rehabilitation outcomes (self-efficacy, functional exercise compliance, hip function, activity and social participation, anxiety and depression, and quality of life). METHODS: A prospective randomized controlled trial with a repeated-measures, two-group design was conducted in a grade A general hospital in Guangdong Province, China. A total of 150 participants with a unilateral total hip replacement were recruited via convenience sampling. Participants were randomly assigned to either the self-efficacy enhancing intervention group (n = 76) or the control group (n = 74). The intervention encompassed a face-to-face education before discharge and four telephone-based follow-ups in six months after surgery. Researchers collected baseline data on one to three days after surgery, and outcomes data were collected one, three, and six months after surgery. RESULTS: Average age (deviation) in intervention and control group were 58 (10.32) and 59 (10.82), respectively. After six months, intervention group scored 86.83 ± 5.89 in rehabilitation self-efficacy, significantly higher than control group (72.16 ± 6.52, t = -10.820, p < 0.001) and their hip function has turned to "excellent" (90.52 ± 4.03), while that of the latter was limited to a "middle" level (78.47 ± 7.57). Statistically significant differences were found in secondary outcomes (p < 0.001). The advantage of intervention in improving quality of life was seen in the long term rather than in the early postoperative period. CONCLUSIONS: The self-efficacy-enhancing intervention performed by nurses induced better exercise compliance and physical, psychological, and social functions after hip replacement compared with routine care. We recommend such interventions to be combined with routine care soon after hip replacement. Further research should focus on the social participation of patients with hip replacement. Trial registration Retrospectively registered at Chinese Clinical Trial Registry (31/01/2020, No. ChiCTR2000029422, http://www.chictr.org.cn/index.aspx ).

Co-cultured Lepista sordida and Pholiota nameko polysaccharide-iron(iii) chelates exhibit good antioxidant activity.

In the present study, the structural characteristics and antioxidant activities of polysaccharide from the co-cultured Lepista sordida and Pholiota nameko and its polysaccharide-iron(iii) chelates were determined. Two polysaccharide fractions named CP-1 and CP-3 were isolated previously from polysaccharide of the fermentation liquid of the co-cultured Lepista sordida and Pholiota nameko. And their chemical structures were measured by FT-IR infrared spectroscopy, TG analysis, X-ray diffraction and 1H NMR spectroscopy. The results suggested that polysaccharides were chelated with iron(iii) by -OH and -COOH groups, forming a stable structure of ß-FeOOH and improving crystallinity. Furthermore, the antioxidant activities of polysaccharide-iron(iii) chelates exhibited stronger hydroxyl radical and superoxide radical scavenging activity than the polysaccharides. Therefore, the polysaccharide-iron(iii) chelates could be used as a potential iron supplement.

Betatrophin for diagnosis and prognosis of mothers with gestational diabetes mellitus.

OBJECTIVES: Betatrophin is a widely used diagnostic marker for type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational DM (GDM) is unclear. We evaluated the relationship between betatrophin and the risk of GDM as well as the ability of betatrophin to predict postpartum type 2 DM (PDM). METHODS: In total, 386 patients were categorized into those with and without PDM. All underwent the oral glucose tolerance test while pregnant. Betatrophin was assessed to examine the diagnostic characteristics of GDM. RESULTS: The betatrophin concentration was remarkably higher in patients with than without GDM. The patients were categorized into three groups; those with a betatrophin concentration of 300 to 600 pg/mL and >600 pg/mL had a higher risk of GDM after adjusting for body mass index, age, homeostatic model assessment-insulin resistance (HOMA-IR) concentration, and betatrophin concentration than those with a betatrophin concentration of <300 pg/mL. The HOMA-IR concentration tended to increase as the betatrophin concentration increased, and betatrophin was independently associated with GDM after adjusting for confounders. The betatrophin concentration was higher among pregnant patients with than without PDM. CONCLUSIONS: Betatrophin has high sensitivity but low specificity for diagnosing GDM and may be a promising predictor of PDM.

MicroRNA-149 is associated with clinical outcome in human neuroblastoma and modulates cancer cell proliferation through Rap1 independent of MYCN amplification.

PURPOSE: We evaluated the clinical relevance of microRNA-149 (miR-149) in neuroblastoma (NB) and its functional roles in regulating NB proliferation in vitro. METHODS: QRT-PCR was used to evaluate miR-149 expression in NB cell lines and primary NB tumors. Association between endogenous miR-149 expression in primary NB tumors and their host patients' clinicopathological factors and overall survival (OS) were statistically evaluated. In SH-SY5Y, an MYCN-non-amplified, and LAN5, an MYCN-amplified NB cell lines, miR-149 was either upregulated or downregulated by lentiviral transduction, to evaluate its effect on NB proliferation in vitro. Possible downstream target of miR-149, Ras-related protein 1 (Rap1), was evaluated by qRT-PCR and western blot in lentiviral-transduced NB cells. Moreover, Rap1 was either upregulated or downregulated in lentiviral-transduced NB cells to further evaluate its effect on miR-149-mediated NB proliferation in vitro. RESULTS: MiR-149 is markedly downregulated in both in vitro NB cell lines and in vivo NB primary tumors. Low miR-149 expression is predominantly associated with Stage 3 or 4 primary NB tumors, and poor OS among NB patients. In SH-SY5Y and LAN5 cells, lentivirus-induced miR-149 upregulation inhibited, whereas miR-149 downregulation promoted NB proliferation in vitro, despite MYCN-amplification status. Rap1 expression, at both mRNA and protein levels, was inversely associated with miR-149 in NB. In addition, Rap1 upregulation or downregulation reversely regulated miR-149-mediated NB proliferation in vitro. CONCLUSION: MiR-149 is downregulated in NB and closely associated with NB patients' clinical outcome. MiR-149 also functionally modulates NB cell proliferation in vitro, possibly through inverse-regulation on Rap1.