Protective Effect of Vitamin K2 (MK-7) on Acute Lung Injury Induced by Lipopolysaccharide in Mice.

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

Application of role reversal and standardized patient simulation (SPS) in the training of new nurses.

PURPOSE: To explore the effect of role reversal and standardized patient simulation on the training of new nurses. METHOD: This study was conducted in a territory hospital in China between August 2021 and August 2022. The selected staff were all newly recruited and trained nurses, with a total of 58 cases. This study is a randomised controlled trial. The selected nurses were randomly divided into two groups. One group of 29 nurses (the control group) received routine training and assessment; the other group (the experimental group) was given role reversal combined with a standardized vertebral patient training examination. The implementation effects of different training and assessment methods were compared and analysed. RESULTS: Before the training, the core competence scores of nurses in the two groups were lower, and there was no significant data difference (P > 0.05). After training, the core competence scores of nurses were improved, and the score of nurses in the experimental group was 165.49 ± 22.34. The difference was statistically significant when compared with the score of nurses in the control group (P < 0.05), indicating that nurses in the experimental group had better abilities. At the same time, the satisfaction of the two groups of nurses with the training was 96.55% (experimental group) and 75.86% (control group), and the difference in data was significant (P < 0.05). The satisfaction of the experimental group of nurses was higher, and the training effect was better. CONCLUSION: In the training of new nurses, the combined application of role interchange and standardized patient training and assessment methods has significant effects, which can improve the core competency of nurses and improve the training satisfaction of nurses, which is significant.

Influence path identification of topography, soil, hydrology and landscape on phosphorus buffering capacity in typical agricultural catchments in central subtropical China.

The catchment phosphorus buffering capacity (PBF) determines the pressure-state-response relationship between anthropogenic P inputs and aquatic ecosystems at a catchment scale, and is affected by biogeochemical, hydrological, and ecological catchment characteristics. However, the complex relationship between these catchment characteristic factors and their impact pathways on PBF remains ambiguous, leading to large uncertainty in balancing agricultural productivity and water conservation via improving BF through management practices. In this study, the short-term buffering index, calculated from net anthropogenic P input and riverine P exports, was used to quantify the spatiotemporal variations in PBF in source agricultural catchments in the Dongting Lake basin. Partial least squares structural equation modeling was used to investigate the relationship between the PBF and the catchment characteristics. The results indicate that catchment PBF was directly determined by soil properties and hydrological conditions, while landscape patterns significantly mediated the effects of topography on soil and hydrology. Considering the pathway preferences of the model, landscape patterns could be the priority for characterizing and regulating PBF. According to a change-point analysis, the probability of PBF weakening increases dramatically when the proportion of farmland (Farm%) > 24.6%, degree of patch interspersion (Contagion index) < 64.5%, and Perimeter-Area Ratio Distribution (PARA) > 348.7. These findings provide new insights into catchment buffering mechanisms and can be used to promote the simultaneous achievement of agricultural production and environmental conservation goals.

Multi-spatial scale effects of multidimensional landscape pattern on stream water nitrogen pollution in a subtropical agricultural watershed.

Multidimensional (coupled land use, soil properties, and topography) landscape effects on stream water nitrogen (N) are complex and scale-dependent. However, studies that identify critical buffer zones that explain large variations in riverine N, and estimate specific thresholds of multidimensional landscape patterns at the class level, result in a sudden changes in riverine N pollution, are still limited. Here, a new multidimensional landscape metric that combined land use, soil properties, and topography effects was applied to various riparian buffer zones and sub-watershed scales, and their relationships to riverine N levels were investigated. We used stream water ammonium-N, nitrate-N, and total-N concentrations datasets, from 2010 to 2017, in the nine subtropical sub-watersheds in China. The results of model selection and model averaging in ordinary least squares regressions, indicated that the riparian buffer zone with widths of 400 m, had more pronounced influence on water NH4-N and TN levels than at other scales. Within the 400 m buffer zone, the key landscape metrics for NH4-N, NO3-N and TN concentrations in stream water were different, and explained up to 43.35%-76.55% (adjusted R2) of the total variation in river N levels. When ENN_MNClass17 below 39-56 m, PDClass8 above 4.63-6.55 n/km2, PLANDClass27 above 23-29%, and CONTIG_MNClass42 below 0.35-0.37% within the 400 m buffer zone, riverine NH4-N and TN would be abruptly increased. This study provided practical ideas for regulation regarding landscape management linked to watershed structure, and identified reference thresholds for multidimensional landscape metrics, which should help reduce riverine N pollution in subtropical China.

Clinical study on flipped classroom and mind map in newly recruited nurses' pre-job training.

BACKGROUND: Traditional pre-job training mainly provides theoretical lectures and operational skill training for new nurses. However, it has a single teaching method, lacks in comprehensiveness and flexibility, and has unsatisfactory teaching effects. The purpose of this article is to evaluate the influence of the flipped classroom and mind map in the pre-job training of newly recruited nurses. METHOD: A total of 92 nurses newly recruited in 2019 were included in the present study and randomly divided into two groups: the intervention group and the control group (n = 46, each). An ordinary training program was applied in the control group, and the flipped classroom + mind map training method was applied in the intervention group. All the new nurses were evaluated using the autonomous learning ability scale before and after pre-job training. RESULTS: The results of the present study showed that before the pre-job training, the total scores of independent learning ability, learning motivation, self-management ability, learning cooperation ability and information quality of nursing staff were similar in the control group and the intervention group; the differences were not statistically significant (P > 0.05). After the application of different training methods, the total score of independent learning ability (84.95 ± 5.146 vs. 66.73 ± 11.213), learning motivation (28.65 ± 3.198 vs. 22.78 ± 5.995), self-management ability (24.97 ± 3.586 vs. 17.89 ± 4.153), learning and cooperation ability (14.391 ± 1.584 vs. 12.17 ± 2.584) and information quality score (16.93 ± 1.306 vs. 13.89 ± 2.651) in the intervention group were significantly higher than in the control group; the differences were statistically significant (P < 0.05). CONCLUSION: The flipped classroom + mind map training method can effectively improve the autonomous learning ability of newly recruited nurses.

[Role of prostaglandin E2 in the modulation of renal water transport].

Prostaglandin E2 (PGE2), a bioactive lipid mediator, is one of the most important locally acting factors involved in a variety of physiological and pathophysiological processes. PGE2 binds with four EP receptors (EP1-4) to activate G protein-coupled receptor signaling responses. Recent functional and molecular studies have revealed that PGE2 plays an essential role in regulation of renal fluid transport via a variety of mechanisms. The water balance mainly depends on the regulation of aquaporin-2 (AQP2) by arginine vasopressin (AVP) in renal collecting duct principal cells. In recent years, increasing evidence suggests that PGE2 plays an important role in renal water reabsorption in the collecting ducts. In this paper, we reviewed the role of PGE2 and its receptors in the regulation of water reabsorption in the kidney, which may provide a new therapeutic strategy for many diseases especially nephrogenic diabetes insipidus.

Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice.

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.

Design and synthesis of tetrahydropyridopyrimidine derivatives as dual GPR119 and DPP-4 modulators.

Based on the approach of merged pharmacophores of GPR119 agonists and DPP-4 inhibitors, a series of tetrahydropyridopyrimidine compounds were designed as dual GPR119 and DPP-4 modulators with hypoglycemic activity. Seven fragments extracted from DPP-4 inhibitors were hybridized with the scaffold of tetrahydropyridopyrimidine. Among them, compound 51 displayed most potent GPR119 agonistic activity (EC50 = 8.7 nM) and good inhibition rate of 74.5% against DPP-4 at 10 µM. Furthermore, the blood glucose AUC0-2h of 51 was reduced to 19.5% in the oral glucose tolerance test (oGTT) at the dose of 30 mg/kg in C57BL/6N mice, which was more potent than that of vildagliptin (16.4%) at the same dose. The docking study of compound 51 with DPP-4 indicated GPR119 agonists could inhibit DPP-4 to serve as dual GPR119 and DPP-4 modulators.

Enhanced nitrogen removal and quantitative analysis of removal mechanism in multistage surface flow constructed wetlands for the large-scale treatment of swine wastewater.

Constructed wetlands have recently been studied as a form of green infrastructure for the enhanced removal of nitrogen (N). This study aimed to demonstrate the use of multistage surface flow constructed wetland (SFCW) for treatment of swine wastewater. The results showed chemical oxygen demand (COD), total nitrogen (TN), NH4+, and NO3- removal rates of 16.3 g m-2 d-1, 9.14 g m-2 d-1, 7.75 g m-2 d-1, and 45.49 mg m-2 d-1, respectively. The sediment and plant absorption N rates were 2.44 g m-2 d-1, and 1.24 g m-2 d-1, respectively. Moreover, the microbial process which is the primary process, by which N is removed, accounted for 56.75-65.35%. Quantitative polymerase chain reaction (qPCR) revealed the highest microbial abundance in the segment of the SFCW with high N concentration. Ammonia-oxidizing bacteria (AOB) and nirK could be primarily responsible for the high removal rate of N. Factors like pH, DO, COD, N, and OM play an important role in influencing microbial abundance. It is suggested that the multistage SFCW has a promising future for the large scale treatment of swine wastewater.

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression.

BACKGROUND/AIMS: Emerging evidence suggests a close link between gut microbiota and non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the association between gut microbiota and the DNA methylation of adiponectin (an adipocyte-specific adipocytokine) in rats, following diet-induced NAFLD. METHODS: 50 male SD rats were randomly divided into five groups with or without a high fat diet (HFD), antibiotics, and probiotics, in order to establish an imbalanced gut microbiota and probiotic treatment model in NAFLD rats. After 13 weeks of treatment, blood, liver, and cecal tissue samples were collected. Serum lipids, liver function indexes by biochemical analyzers, and changes in liver pathology with hematoxylin-eosin (HE) and masson staining were detected. Furthermore, the serum adiponectin by enzyme-linked immunosorbent assay (ELISA) and liver adiponectin methylation levels in the promoter regions by pyrophosphate sequencing were determined. High throughput Illumina sequencing targeted microbial 16S genes, bioinformatics and statistical analysis identified cecal-associated gut microbiota. RESULTS: HFD with antibiotic exposure showed the most severe steatohepatitis and a severe gut microbiota alteration. Reduced bacterial diversity was also seen and the abundances of Firmicutes, Lactobacillus, Cyanobacteria, Acidobacteria, Chlamydiae, Chlamydiales, Rubrobacteria, Verrucomicrobia, Blautia, Shewanella, Bacteroides, Bacteroides acidifaciens, and Bacteroides uniformis, were shown to be partly reversed by probiotic treatment. Decreased serum adiponectin levels and increased DNA methylation levels of adiponectin promoter regions were also markedly associated with the NAFLD progression during gut microbiota alteration. CONCLUSION: Our results suggested that both gut microbiota alteration and adiponectin variability may be drivers of NAFLD progression and that targeting the gut microbiota, such as via administration of a probiotic, may delay NAFLD progression via adiponectin.

Diversity and distribution of bacteria in a multistage surface flow constructed wetland to treat swine wastewater in sediments.

Managing waste produced from swine farming operations is a significant agricultural and environmental challenge. Confined animal feeding operations continually generate large amounts of animal waste, which necessitates adequate waste management systems. This study examines the use of multistage surface flow constructed wetlands (SFCWs) to treat pig farm sewage. The wastewater removal rate, sediment deposits, physicochemical properties, and microbial community compositions of each segment of a SFCW were examined. The results indicated that removal rates of chemical oxygen demand (COD), total nitrogen (TN), NH4+, NO3-, and total phosphorus (TP) were 89.8%, 97.9%, 98.2%, 87.6%, and 96.4%, respectively, in the multistage SFCW. The general trend showed increase in the dissolved oxygen (DO) concentrations and oxidation reduction potential (Eh) from the beginning of the SFCW to its end. Sediment concentrations of N and P in each segment of the SFCW generally decreased, suggesting their accumulation in each segment. High-throughput sequencing indicated that the bacterial diversity increased over time. Proteobacteria, Bacteroidetes, Chloroflexi, and Firmicutes were dominant in multistage SFCW bacterial communities at the phylum level. Results further indicate that DO and Eh are major environmental factors that influence the bacterial community distribution. Overall, our findings suggest that multistage SFCWs not only improve contaminant removal but also change the bacterial community composition and promote bacterial community diversity.

Prostaglandin E2 in the Regulation of Water Transport in Renal Collecting Ducts.

The kidney plays a central role in the regulation of the body water balance. The process of targeting the water channel aquaporin-2 (AQP2) on the apical plasma membrane of the collecting duct (CD) principal cells is mainly regulated by the antidiuretic peptide hormone arginine vasopressin (AVP), which is responsible for the maintenance of water homeostasis. Recently, much attention has been focused on the local factors modulating renal water reabsorption by AQP2 in the collecting ducts, especially prostaglandin E2 (PGE2). PGE2 is a lipid mediator involved in a variety of physiological and pathophysiological processes in the kidney. The biological function of PGE2 is mainly mediated by four G-protein-coupled receptors, namely EP1-4, which couple to drive separate intracellular signaling pathways. Increasing evidence demonstrates that PGE2 is essential for renal water transport regulation via multiple mechanisms. Each EP receptor plays a unique role in regulating water reabsorption in renal collecting ducts. This brief review highlights the role of PGE2 in the regulation of water reabsorption and discusses the involvement of each EP receptor subtype in renal collecting duct. A better understanding of the role of PGE2 in renal water transport process may improve disease management strategies for water balance disorders, including nephrogenic diabetes insipidus.

Visible-Light-Induced Photocatalytic Aerobic Oxidation/Povarov Cyclization Reaction: Synthesis of Substituted Quinoline-Fused Lactones.

A one-step construction of quinoline-fused lactones was achieved by visible-light-induced photocatalytic aerobic oxidation/Povarov cyclization reaction. This method provides a new access to the synthesis of important fused heterocycles under mild reaction conditions.

Visible Light-Induced Radical Rearrangement to Construct C-C Bonds via an Intramolecular Aryl Migration/Desulfonylation Process.

A highly efficient intramolecular selective aryl migration/desulfonylation of 2-bromo-N-aryl-N-(arenesulfonyl)amide via visible light-induced photoredox catalysis has been accomplished. This approach allows for the construction of a variety of multisubstituted N,2-diarylacetamide under mild reaction conditions.

Clinical characteristics of Clostridium difficile-associated diarrhea among patients in a tertiary care center in China.

OBJECTIVE: This study investigated the incidence, risk factors, and clinical characteristics of Clostridium difficile-associated diarrhea (CDAD) in Chinese patients. METHODS: Fecal specimens of patients with antibiotic-associated diarrhea (AAD) were collected to test C. difficile toxin A and B using enzyme-linked fluorescent assay to identify CDAD. By adopting a nested case-control design, the matched people (ratio 1:3) without AAD were included as controls. RESULTS: Out of 56,172 inpatients, 39,882 (71.0%) used antibiotics, 470 suffered from AAD, and 93 were diagnosed with CDAD. The incidence of nosocomial CDAD was 166 per 100,000. The proportion of CDAD in AAD was 19.8%. CDAD patients presented with more severe clinical manifestations and exhibited more concurrent illness. Logistic regression analysis showed the risk factors of CDAD: advanced age, nasogastric tube-feeding, high APACHE II scores, high level of serum C-reaction protein, low level of serum albumin, severe underlining disease or comorbidity, and number of antibiotic intake. Twenty-nine patients (31.2%) were cured with vancomycin, 54 (58.1%) were cured after dual therapy of vancomycin plus metronidazole, 7 (7.5%) died of underlying diseases aggravated with CDAD, and 3 (3.2%) were transferred to other hospitals for personal reasons. CONCLUSION: The incidence of nosocomial CDAD in China was high. Some risk factors could predispose CDAD.

Accelerated partial hepatectomy-induced liver cell proliferation is associated with liver injury in Nur77 knockout mice.

Nur77, encoded by Nr4a1 (alias Nur77), plays roles in cell death, survival, and inflammation. To study the role of Nur77 in liver regeneration, wild-type (WT) and Nur77 knockout (KO) mice were subjected to standard two-thirds partial hepatectomy (PH). Nur77 mRNA and protein levels were markedly induced at 1 hour after PH in WT livers, coinciding with ERK1/2 activation. Surprisingly, Nur77 KO mice exhibited a higher liver-to-body weight ratio than WT mice at 24, 48, and 72 hours after PH. Nur77 KO livers exhibited increase in Ki-67-positive hepatocytes at 24 hours, with early induction of cell-cycle genes. Despite accelerated regeneration, Nur77 KO livers paradoxically incurred necrosis, hepatocyte apoptosis, elevated serum alanine aminotransferase activity, and Kupffer cell accumulation. Microarray analysis revealed up-regulation of genes modulating inflammation, cell proliferation, and apoptosis but down-regulation (due to Nur77 deficiency) of glucose and lipid homeostasis genes. Levels of proinflammatory cytokines IL-6, IL-12, IL-23, and CCL2 were increased and levels of anti-inflammatory IL-10 were decreased, compared with WT. Activated NF-κB and STAT3 and mRNA levels of target genes Myc and Bcl2l1 were elevated in Nur77 KO livers. Overall, Nur77 appears essential for regulating early signaling of liver regeneration by modulating cytokine-mediated inflammatory, apoptotic, and energy mobilization processes. The accelerated liver regeneration observed in Nur77 KO mice is likely due to a compensatory effect caused by injury.

Serum ubiquitin C-terminal hydrolase L1 as a biomarker for traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVE: Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker of traumatic brain injury (TBI). However, previous studies on levels of UCH-L1 in serum remain inconsistent. This systematic review and meta-analysis were conducted on observational studies that reported the association between serum UCH-L1 levels and TBI. METHODS: Studies were identified by searching PubMed and ISI Web of Science up to February 2015. For the continuous outcomes, we calculated the weighted mean difference and 95% confidence interval. The statistical analysis was performed by RevMan 5.1 and Stata 12 software. Only case-control studies were included if they had data on serum UCH-L1 levels in TBI patients and healthy controls. Funnel plot and Egger's regression test were applied to assess the potential publication bias. RESULTS: Of the 145 selected studies, 11 observational studies (including 9 case-control and 2 case-crossover studies) met the selection criteria, containing a total of 1138 TBI cases and 1373 controls. Finally, 5 case-control studies (including 673 TBI and 1004 controls) were eligible for the present meta-analysis. The results of our study showed that there was a significant increase in serum UCH-L1 levels in patients with TBI compared to controls (weighted mean difference, 0.96; 95% confidence interval, 0.31-1.61; P = .004). CONCLUSION: In conclusion, TBI cases had higher serum UCH-L1 concentrations than matched controls. This reinforces the conceptualization of UCH-L1 as a potential biomarker of TBI.

TMDL for phosphorus and contributing factors in subtropical watersheds of southern China.

Water eutrophication, particularly that caused by phosphorus runoff, is of major concern in China due to the serious threats it poses to watershed environments. We investigated one forested and nine agricultural watersheds with areas of 9-5212 ha in a hilly region of Hunan Province in a subtropical region of southern China from 2010 to 2012 to study total phosphorus (TP) loads and contributing factors. The annual TP loads varied from 35.7 to 222.1 kg P km(-2) year(-1) among the different watersheds, with the rainy season of spring and summer accounting for 56.3-82.0% of TP loss. The highest total maximum daily load (TMDL, 0.5 kg P km(-2) day(-1)) and existing exported daily TP loads (DTPL, 1.8 kg P km(-2) day(-1)) were observed under high flow and moist flow conditions in the ten watersheds. However, the target daily reduction ratios for the DTPLs to reach the water quality standard of 0.05 mg P L(-1) varied little with flow condition in the stream but depended on the type of watershed, i.e., <50, <80, and 80-90% for forested, agricultural, and livestock-dominated watersheds, respectively. Gray relational analysis (GRA) suggested that livestock density was the most important factor for watershed TP load under various hydrologic conditions, while livestock density (LD), soil available phosphorous (SAP), cropland percentage, and mean shape index (SHMN) were notable factors for daily reduction rate (DRR) under high and moist flow conditions. Therefore, to protect the local watershed environments, watershed management approaches that include the regulation of livestock production are recommended as the most effective means of reducing P loads at the watershed scale in subtropical areas of southern China.

The effect of miRNA-122 in regulating fat deposition in a cell line model.

Accumulating evidence supports the role of miR-122 in fatty liver disease. We investigated miR-122 expression in a steatotic hepatocyte model, the effect of miR-122 over-expression and inhibition in the pathogenesis. Human hepatic cell line L02 was induced with oleic acid to establish the steatotic hepatocyte model. Intracellular lipid content was observed with laser scanning confocal microscope (LSCM), and triglyceride content was determined with kits. Total RNA was extracted and reversely transcribed into cDNA. miR-122 expression was measured using qRT-PCR. Subsequently, miR-122 mimic and miR-122 inhibitor were transfected into steatotic hepatocytes to observe their effect on intracellular lipid content. The lipid fluorescence intensity and triglyceride content within the steatotic hepatocytes were significantly higher than those in normal control (860.01 ± 26.52 vs. 257.77 ± 29.69 and 3.47 ± 0.12 vs. 1.85 ± 0.02 at 24 h) (P < 0.01). miR-122 expression in steatotic hepatocytes was down-regulated compared with that in control (2-ΔCt value: 0.0286 ± 0.0078 vs. 0.0075 ± 0.0012) (P ≪ 0.01). After transfection, miR-122 expression (2-ΔCt value) in the miR-122 mimic group increased 2.96-fold compared with that in control, and its lipid fluorescence intensity was significantly lower than that in control (790.92 ± 46.72 vs. 1,022.16 ± 49.66) (P < 0.01). Nevertheless, miR-122 expression decreased 3.45-fold in the miR-122 inhibitor group compared with that in control, and its fluorescence intensity was significantly higher than that in control (1,386.49 ± 40.34 vs 1,022.16 ± 49.66)(P ≪ 0.01). We concluded that miR-122 was down-regulated in steatotic hepatocytes model. The pathogenesis of hepatocyte steatosis was enhanced by miR-122 mimic and reduced with miR-122 inhibitor.

G-A variant in miR-200c binding site of EFNA1 alters susceptibility to gastric cancer.

MicroRNAs (miRNAs) post-transcriptionally modulate gene expression by binding to complementary sites at 3'-untranslated regions (3'UTRs) of their target messenger RNAs (mRNAs). Genetic variations in miRNA binding sites may alter individual susceptibilities to many cancers. However, whether miRNA binding site single nucleotide polymorphisms (SNPs) interfere with gastric cancer (GC) susceptibility has not been reported. In this case-control study including 525 GC patients and 501 controls, we selected three miRNA binding site SNPs located in 3'UTRs of genes involved in GC to investigated their associations with GC susceptibility. We identified that rs12904 in ephrin-A1 (EFNA1) gene was significantly associated with risk of GC, with the OR for carrying AG or GG genotype being 0.65 (P = 0.002, OR 0.65; 95% CI, 0.50-0.85) compared with AA genotype. Specifically, we found that rs12904 is in strong linkage disequilibrium (LD) with rs4072037, a susceptibility variant reported by previous genome-wide association study (GWAS). No significant associations were observed for the other two SNPs (rs699517 in TYMS and rs1042542 in BIRC5). Furthermore, luciferase assays indicated EFNA1 as the target of hsa-miR-200c and rs12904 G > A change resulted in altered regulation of luciferase expression. In addition, rs12904 AA genotype was associated with increased expression of EFNA1 mRNA compared with AG or GG genotype in the cancer tissues from 48 patients. Taken together, these findings indicate that the miR-200c binding site SNP (rs12904 G > A) in the 3'UTR of EFNA1 can modulate EFNA1 expression and is associated with GC susceptibility. Larger replication studies are needed to confirm our findings.