An essential endoplasmic reticulum-resident N-acetyltransferase ortholog in Plasmodium falciparum.

N-terminal acetylation is a common eukaryotic protein modification that involves the addition of an acetyl group to the N-terminus of a polypeptide. This modification is largely performed by cytosolic N-terminal acetyltransferases (NATs). Most associate with the ribosome, acetylating nascent polypeptides co-translationally. In the malaria parasite Plasmodium falciparum, exported effectors are thought to be translated into the endoplasmic reticulum (ER), processed by the aspartic protease plasmepsin V and then N-acetylated, despite having no clear access to cytosolic NATs. Here, we used inducible gene deletion and post-transcriptional knockdown to investigate the primary ER-resident NAT candidate, Pf3D7_1437000. We found that it localizes to the ER and is required for parasite growth. However, depletion of Pf3D7_1437000 had no effect on protein export or acetylation of the exported proteins HRP2 and HRP3. Despite this, Pf3D7_1437000 depletion impedes parasite development within the host red blood cell and prevents parasites from completing genome replication. Thus, this work provides further proof of N-terminal acetylation of secretory system proteins, a process unique to apicomplexan parasites, but strongly discounts a promising candidate for this post-translational modification.

Proteomic and metabolomic proof of concept for unified airways in chronic rhinosinusitis and asthma.

BACKGROUND: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) with comorbid asthma remains unclear. OBJECTIVE: To assess upper and lower airway unity and identify a possible common pathogenesis in CRSwNP with asthma. METHODS: This study analyzed the expression of proteins and metabolites in nasal lavage fluid cells (NLFCs) and induced sputum cells (ISCs). Differentially expressed proteins and their function-related metabolites in the upper and lower airways of patients having CRSwNP with or without asthma were identified; relevant signaling pathways were analyzed, and key pathway-related proteins were identified. Parallel reaction monitoring was used to verify these target proteins. RESULTS: Protein or metabolite expression between NLFCs and ISCs was highly correlated and conservative on the basis of expression profiles and weighted gene coexpression network analysis. There were 17 differentially coexpressed proteins and their function-related 13 metabolites that were identified in the NLFCs and ISCs of CRSwNP, whereas 11 proteins and 11 metabolites were identified in CRSwNP with asthma. An asthma pathway was involved in the copathogenesis of upper and lower airways in whether CRSwNP or CRSwNP with asthma. The asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase, as the core of the protein-metabolism interaction networks between the upper and lower airways, were both highly coexpressed in NLFCs and ISCs in patients having either CRSwNP or CRSwNP with asthma by parallel reaction monitoring validation. CONCLUSION: Proteomics and metabolomics reveal upper and lower airway unity. Asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase from the upper airway could be used to assess the potential risk of lower airway dysfunction in CRSwNP.

Rapid Nucleic Acid Detection of Listeria monocytogenes Based on RAA-CRISPR Cas12a System.

Listeria monocytogenes (L. monocytogenes) is a food-borne pathogenic bacteria that frequently contaminates animal-derived food and low-temperature preserved food. Listeriosis caused by its infection has a high mortality rate and poses a serious threat to human health. Therefore, it is crucial to establish a sensitive, rapid and easy-to-operate technique. In this study, a Recombinase Aided Amplification (RAA) assisted CRISPR/Cas12a (RAA-CRISPR/Cas12a) fluorescence platform was established for highly sensitive nucleic acid detection of L. monocytogenes. The established RAA-CRISPR/Cas12a showed high sensitivity and high specificity, with the sensitivity of 350 CFU/mL and 5.4 × 10-3 ng/µL for pure bacterial solution and genomic DNA, and good specificity for 5 strains of Listeria spp. and 14 strains of other common pathogenic bacteria. L. monocytogenes could be detected at an initial concentration of 2.3 CFU/25g within 2 h of enriching the beef in the food matrix, and this method could be applied to food samples that were easily contaminated with L. monocytogenes The results of RAA-CRISPR/Cas12a could be observed in 5 min, while the amplification was completed in 20-30 min. The speed and sensitivity of RAA-CRISPR/Cas12a were significantly higher than that of the national standard method. In conclusion, the RAA-CRISPR/Cas12a system established in this study has new application potential in the diagnosis of food-borne pathogens.

Risk Factors for Acute Rhinosinusitis in Childhood Asthma.

INTRODUCTION: Specific pathogen infections associated with acute rhinosinusitis (ARS) in infants are risk factors for allergic asthma in adolescents. However, the risk factors for ARS onset remain largely unknown in asthmatic children. In this study, we aim to investigate the risk factors for ARS in childhood asthma. METHODS: This study retrospectively compared and analyzed the clinical characteristics of asthmatic children with (n = 194) or without ARS (n = 799). Univariate regression analyses were performed to identify ARS-associated risk factors in asthmatic children, and subsequent multivariate backward stepwise logistic regression analyses were performed to identify independent risk factors. RESULTS: The onset age, values of blood eosinophils (EOS) (%), and total IgE were significantly lower in patients with ARS than in those without ARS. Moreover, the proportions of patients allergic to Dermatophagoides pteronyssinus (d1) and Dermatophagoides farinae (d2) were significantly smaller in children with ARS (all p values <0.05). Univariate analyses showed that an older onset age, a higher body mass index, a higher value of blood EOS (%) were protective factors, while a higher value of blood lymphocytes (%) and a higher degree of sensitization to d1 and d2 were risk factors for ARS. Further backward stepwise multivariate logistic regression analyses confirmed that a younger onset age and allergic sensitization to d1 were independent risk factors for ARS in childhood asthma. CONCLUSION: Younger onset age and allergic sensitization to d1 are risk factors for the onset of ARS in childhood asthma, so allergen intervention should be performed as early as possible in asthmatic children.

Risk Factors for Abnormal Small Airway Function Indicators in Nasal Polyp Patients with and without Asthma.

INTRODUCTION: Small airway dysfunction (SAD) is associated with type 2 inflammation in patients who have non-asthmatic chronic rhinosinusitis with nasal polyps (CRSwNPs); however, the risk factors for abnormal small airway function indicators in CRSwNP patients with and without asthma remain unclear. METHODS: We retrospectively analyzed 41 asthmatic and 109 non-asthmatic CRSwNP patients. Clinical characteristics were compared between groups, correlations between small airway function and clinical parameters were calculated, and independent risk factors for every small airway indicator were identified in each group. RESULTS: Asthmatic CRSwNP patients had significantly reduced small airway function, and the proportion of patients with SAD was higher in asthmatic CRSwNP patients (65.85%) than in patients without asthma (9.17%). With regard to specific airway function indicators, age and a patient's blood eosinophil (%) were identified as independent risk factors for lower FEF50% %pred and FEF25-75% pred, with age being an independent risk factor for FEF75% %pred in asthmatic CRSwNP patients. In non-asthmatic CRSwNP patients, allergic rhinitis comorbidity was found to be an independent risk factor for FEF50% %pred, FEF75% %pred, and FEF25-75% %pred. CONCLUSION: Physicians should pay greater attention to risk factors for abnormal small airway function indicators in patients with CRSwNPs to prevent the occurrence of SAD.

Total serum immunoglobulin E (IgE) as an effective predictor for identifying allergic asthma in childhood asthma.

Background: Allergic asthma accounts for the majority of childhood asthma and is characterized by elevated total serum immunoglobulin E (tIgE). However, whether tIgE can predict allergic asthma in childhood asthma remains unclear. Objective: The purpose of this study was to identify the potential of tIgE for predicting allergic asthma in childhood asthma and provide a reliable reference value. Methods: Clinical characteristics and the level of tIgE from children with asthma in 2008 (n = 280) and 2018 (n = 479) were retrospectively analyzed. Receiver operating characteristic (ROC) curves were generated to determine the optimal cutoff points and predictive values of tIgE for diagnosing allergic asthma in childhood asthma in 2008 and 2018, and the diagnosis efficiency of tIgE was validated in 491 children with asthma of 2019. Results: The level of tIgE was significantly lower in 2018 than that in 2008. Receiver operating characteristic curves showed cutoff values of tIgE were 142.50 IU/mL (area under the curve [AUC] = 0.864) and 96.25 IU/mL (AUC = 0.835) for diagnosing allergic asthma in 2008 and 2018, respectively. The level of tIgE from children with asthma in 2019 was similar to that in 2018 but was significantly lower than that in 2008. We further used the cutoff value of tIgE = 96.25 IU/mL to validate the diagnosis efficiency in children with asthma of 2019 and found that the diagnostic accuracy, sensitivity, specificity of allergic asthma, and the Youden index reached 76.78%, 76.10%, 78.03%, and 0.540, respectively. Conclusion: The tIgE value is an effective predictor for diagnosing allergic asthma in childhood asthma, with tIgE = 96.25 IU/mL being the recommended limit.

Network Pharmacology-Based Approach for Investigating the Role of Xanthii Fructus in Treatment of Allergic Rhinitis.

Xanthii Fructus (XF) has been used for treatment of allergic rhinitis (AR), but its pharmacological mechanism of action remains unclear. We aimed to explore the potential mechanism of XF in treatment of AR by using a network pharmacology approach combined with in vivo verification experiments in this study. We identified 945 AR-related pathogenic genes, 11 active components in XF and 178 targets of those active components by corresponding databases. Finally, 54 targets of active components from XF in treatment of AR were identified by the Protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, among which Tumor Necrosis Factor (TNF), Mitogen-activated Protein Kinase 3 (MAPK3), Prostaglandin G/H Synthase 2 (PTGS2), Epidermal Growth Factor Receptor (EGFR) showed strongest interactions. The molecular docking analysis showed that moupinamide could bind to EGFR at LEU704 and LEU703, and PTGS2 at TRP387; 24-Ethylcholest-4-en-3-one was identified to bind to MAPK3 at THR347. The validation of quantitative real-time reverse transcription PCR (RT-PCR) showed that XF decreased the levels of MAPK3, PTGS2, and EGFR expression in the nasal mucosa from AR mice gavaged with an XF water decoction. Meanwhile, the levels of interleukin (IL)-4, IL-5 and IL-13were also decreased after the treatment of XF by Enzyme-linked immunosorbent assay (ELISA). Our results provide the pharmacological mechanism and possible intervention targets of XF in treatment of AR.

miR-146a enhances regulatory T-cell differentiation and function in allergic rhinitis by targeting STAT5b.

BACKGROUND: MicroRNA (miR)-146a, as an important immune regulatory factor with an anti-inflammatory effect, plays a crucial role in regulatory T-cell (Tregs) differentiation and function in allergic rhinitis (AR). The present study aimed to investigate the regulatory mechanism employed by miR-146a to control Treg differentiation and function in AR. METHODS: Expression of miR-146a and STAT5b in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from patients with AR was detected by qPCR and Western blotting. Tregs were quantified by flow cytometry in miR-146a knockdown or STAT5b knockdown PBMCs. FOXP3, IL-10, and TGF-ß levels were detected by Western blotting or ELISA in miR-146a knockdown or STAT5b overexpressing PBMCs, as well as in STAT5b knockdown PBMCs overexpressing miR-146a. The effect of miR-146a on STAT5b was observed by luciferase assay and knockdown experiments. RESULTS: Levels of miR146a and STAT5b in the nasal mucosa or PBMCs were significantly lower in the AR group than in the control group. There were significantly fewer Tregs in miR-146a knockdown or STAT5b knockdown PBMCs compared to control PBMCs. Expression of FOXP3, IL-10, and TGF-ß was decreased in the miR-146a knockdown group but increased in the STAT5b overexpression group. In contrast, miR-146a overexpression increased the levels of these factors, but knockdown of STAT5b significantly inhibited this effect. Luciferase assay and knockdown experiments showed that miR-146a bound directly to STAT5b. CONCLUSIONS: miR-146a enhances Treg differentiation and function in AR by positively targeting STAT5b.

Fluorotelomer Alcohols' Toxicology Correlates with Oxidative Stress and Metabolism.

Fluorotelomer alcohols (FTOHs) are widely used as industrial raw materials due to their unique hydrophobic and oleophobic properties. However, because of accidental exposure to products containing FTOHs or with the widespread use of FTOHs, they tend to contaminate the water and the soil. There are reports demonstrating that FTOHs can cause various harmful effects in animals and humans (for example, neurotoxicity, hepatotoxicity, nephrotoxicity, immunotoxicity, endocrine-disrupting activity, and developmental and reproductive toxicities). Oxidative stress is related to a variety of toxic effects induced by FTOHs. To date, few reviews have addressed the relationship between the toxicity of FTOHs and oxidative stress. This article summarises research demonstrating that the toxicity induced by FTOHs correlates with oxidative stress and metabolism. Furthermore, during the metabolic process of FTOHs, a number of cytochrome P450 enzymes (CYP450) are involved and many metabolites are produced by these enzymes, which can induce oxidative stress. This is also reviewed.

An uncommon etiological factor for aspiration pneumonitis caused by spontaneous sphenoid sinus meningoencephalocele with cerebrospinal fluid rhinorrhea: a case report.

BACKGROUND: Aspiration pneumonitis is an inflammatory disease of the lungs which is difficult to diagnose accurately. Large-volume aspiration of oropharyngeal or gastric contents is essential for the development of aspiration pneumonitis. The role of cerebrospinal fluid (CSF) rhinorrhea is often underestimated as a rare etiological factor for aspiration in the diagnosis process of aspiration pneumonitis. CASE PRESENTATION: We present a case of a patient with 4 weeks of right-sided watery rhinorrhea accompanied by intermittent postnasal drip and dry cough as the main symptoms. Combined with clinical symptoms, imaging examination of the sinuses, and laboratory examination of nasal secretions, she was initially diagnosed as spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, and intraoperative endoscopic findings and postoperative pathology also confirmed this diagnosis. Her chest computed tomography showed multiple flocculent ground glass density shadows in both lungs on admission. The patient underwent endoscopic resection of meningoencephalocele and repair of skull base defect after she was ruled out of viral pneumonitis. Symptoms of rhinorrhea and dry cough disappeared, and pneumonitis was improved 1 week after surgery and cured 2 months after surgery. Persistent CSF rhinorrhea caused by spontaneous sphenoid sinus meningoencephalocele was eventually found to be a major etiology for aspiration pneumonitis although the absence of typical symptoms and well-defined risk factors for aspiration, such as dysphagia, impaired cough reflex and reflux diseases. CONCLUSIONS: We report a rare case of aspiration pneumonitis caused by spontaneous sphenoid sinus meningoencephalocele with CSF rhinorrhea, which can bring more attention and understanding to the uncommon etiology for aspiration, so as to make more accurate diagnosis of the disease and early surgical treatment.

A novel sigma class glutathione S-transferase gene in freshwater planarian Dugesia japonica: cloning, characterization and protective effects in herbicide glyphosate stress.

As the top-selling herbicide in the world, glyphosate distributes widely in natural environment and its influence on the ecological security and human health has attracted more and more concern. Glutathione S-transferases (GSTs) are a well-characterized superfamily of isoenzymes for cellular defense against exogenous toxic substances and therefore protect organisms from injury. In this study, the complete cDNA sequence of GST gene (named as Dja-GST) in freshwater planarian Dugesia japonica was firstly cloned by means of RACE method. The full-length Dja-GST comprises of 706 nucleotides which encodes a polypeptide of 200 amino acids. Dja-GST has two representative GST domains at the N- and C-termini. The conservative GST-N domain includes G-site Y8, F9, R14, W39, K43, P52 and S64, while the variable GST-C domain contains H-site K104, V156, D159 and L161. Sequence analysis, phylogenetic tree reconstruction and multiple alignment collectively indicate that Dja-GST belongs to the Sigma class of GST superfamily. Also, GST gene expression profile, GST enzymatic activity and MDA content in response to glyphosate exposure were systematically investigated and the correlations among them were analyzed. The results suggest that glyphosate exposure modified the mRNA transcription and enzymatic activity of GST, as well as the MDA content in planarians, indicating that Dja-GST might play an important part in organisms defending against oxidative stress induced by glyphosate. This work lays a molecular foundation for further exploring the exact functions of Dja-GST and gives an important implication for evaluating the ecological environment effects of herbicide glyphosate.

Biomarkers of Planarian Dugesia japonica in Response to Herbicide Glyphosate Exposure.

As the worldwide top-selling herbicide, glyphosate is ubiquitously distributed in the natural environment, and its influence on the ecological safety and human health has being increasingly concerned. In this study, mRNA expressions of GPX and three heat shock protein genes in freshwater planarian Dugesia japonica in response to glyphosate were determined, and two oxidative stress parameters were measured. The results suggested that GPX activity can be used as a more sensitive biomarker in contrast with GPX gene expression, and mRNA expressions of Hsp70, Hsp90 genes are more sensitive than Hsp40 for planarians in response to glyphosate stress. Besides, the deduced T-AOC as well as varied GPX activity and mRNA expression levels of Hsps also indicated that glyphosate exposure would inhibit antioxidation and induce oxidative stress in D. japonica, while specific antioxidant systems and stress proteins tried to protect cells by their own regulation. The results of this study will be helpful to elucidate the stress response mechanisms of freshwater planarians to herbicide glyphosate.

The effect of bisphenol a exposure onto endothelial and decidualized stromal cells on regulation of the invasion ability of trophoblastic spheroids in in vitro co-culture model.

Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic Jeg-3 spheroids and regulation of endothelial and stromal cells on trophoblastic spheroids invasion, and its possible mechanism were investigated. The results showed that BPA at 10 and 100 µM can inhibit the attachment of Jeg-3 spheroid onto Ishikawa cells. BPA at 1-100 µM also activate ERE-Luc reporter expression in the transfected cells, which was through the ERα, but not ERß or GPR30 binding. Endothelial receptivity ability was harmed by BPA treatment since receptivity markers of LIF, EGF, MUC1 and integrin αVß3 were decreased after BPA treatment. The invasion ability of trophoblastic spheroids generated from Jeg-3 cell line was inhibited by BPA and this effect was mediated through canonical ERs pathway and MMP2/MMP9 down-regulation and TIMP1/PAI-1 up-regulation. Besides, BPA treated decidualized stromal cells suppressed Jeg-3 spheroid outgrowth and invasion in co-culture assay. Our study would give a better understanding on the possible mechanism of BPA effect on human embryo implantation process.

Effects of graphene oxide on cadmium uptake and photosynthesis performance in wheat seedlings.

Graphene oxide (GO) is extensively used in various fields because of its versatility. The presence of GO in the environment enhances the toxicity of toxicants or pollutants. Cadmium (Cd) and GO pollution is a problem in aquatic environment, which should be solved. We investigated the toxic effects of Cd on photosynthesis and oxidative stress in wheat seedlings in the presence of GO, by measuring seedling biomass, Cd content, photosynthesis, reactive oxygen species (ROS) level, antioxidant enzyme activities, and malondialdehyde (MDA) content. At low concentrations, GO alone had limited effects, but at concentrations > 20 mg L-1, seedlings were negatively affected. Under combined Cd-GO treatment, GO was significantly toxic at only 5 mg L-1 concentration, and increasing concentration significantly increased Cd accumulation and decreased biomass. The net photosynthetic rate, stomatal conductance, transpiration rate, primary maximum photochemical efficiency of photosystem II, actual quantum yield, photosynthetic electron transport rate, chlorophyll content, and ribulose-1,5-bisphosphate carboxylase/oxygenase concentration decreased significantly, whereas intercellular CO2 concentration increased significantly. These changes can be attributed to impairment of ROS level, antioxidant enzyme activities, and MDA level, and toxicity mechanisms are suggested to be due to oxidative stress. The resulting damage to the photosynthetic systems and structures likely contributed to the overall decrease in biomass.

MicroRNA-760 Inhibits Doxorubicin Resistance in Hepatocellular Carcinoma through Regulating Notch1/Hes1-PTEN/Akt Signaling Pathway.

Accumulating studies have suggested that microRNA-760 (miR-760) plays an important role in chemoresistance of various cancer cells. However, whether miR-760 regulates the chemoresistance of hepatocellular carcinoma (HCC) remains unclear. In this study, we found that miR-760 was decreased in HCC cell lines, and doxorubicin (Dox) treatment significantly decreased miR-760 expression in HCC cells. Overexpression of miR-760 sensitized HCC cells to Dox-induced cytotoxicity and apoptosis, whereas miR-760 inhibition showed the opposite effects. Notch1 was predicted as a target gene of miR-760. miR-760 negatively regulated Notch1 expression and Notch1/Hes1 signaling. Overexpression of miR-760 increased PTEN expression and decreased the phosphorylation of Akt. Activation of Notch signaling significantly reversed the inhibitory effect of miR-760 on Dox-resistance and abrogated the effect of miR-760 on the PTEN/Akt signaling pathway in HCC cells. Overall, our results demonstrate that miR-760 inhibits Dox-resistance in HCC cells through inhibiting Notch1 and promoting PTEN expression.

Molecular cloning, characterization, expression and enzyme activity of catalase from planarian Dugesia japonica in response to environmental pollutants.

Catalase (CAT) is an important antioxidant enzyme that protects aerobic organisms against oxidative damage by degrading hydrogen peroxide to oxygen and water. CAT mRNAs have been cloned from many species and employed as useful biomarkers of oxidative stress. In the present study, we cloned the cDNA sequence of CAT gene from freshwater planarian Dugesia japonica (designated as DjCAT) by means of RACE method. Sequence analysis and multiple alignment jointly showed that the full-length cDNA sequence consists of 1734 nucleotides, encoding 506 amino acids. Three catalytic amino acid residues of His71, Asn144 and Tyr354, two CAT family signature sequences of a proximal active site signature (60FDRERIPERVVHAKGGGA77) and a heme-ligand signature motif (350RLFSYRDTQ358) are highly conserved, suggesting that the DjCAT belongs to the NADPH and heme-binding CAT family and has similar functions. In addition, the transcriptional level of CAT gene and activity of CAT enzyme upon acute exposure of environmental pollutants glyphosate and 1-decyl-3-methylimidazolium bromide ([C10mim]Br) were investigated systematically. The variation of CAT mRNA expression in D. japonica was quantified by real-time PCR and the results indicated that it was up-regulated after exposure to glyphosate or [C10mim]Br with a dose-dependent manner but not linearly. Even though the variation trend of CAT activity upon glyphosate stress was not monotonously increased and inconsistent with that after [C10mim]Br exposure on day 1 and 3 sampling time, with the duration prolonged to day 5 they both presented a dose-dependent increase and the differences achieved extreme significance in all treated groups compared to the control. These findings suggested that DjCAT plays an important role in antioxidant defense in D. japonica, and the mRNA expression of CAT would also be used as an effective biomarker to monitor the pollution in aquatic environment just like its corresponding enzyme.

MicroRNA-155-5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway.

MicroRNA-155-5p (miR-155-5p) has been reported to play an oncogenic role in different human malignancies; however, its role in hepatocellular carcinoma (HCC) progression is not clearly understood. In this study, we used real-time PCR in 20 rats with chemically-induced HCC, 28 human HCC tissues, and the matched paracarcinoma tissues, and HCC cell lines to determine the expression patterns of miR-155-5p and PTEN mRNA. Algorithm-based and experimental strategies, such as dual luciferase gene reporter assays, real-time PCR and western blots were used to identify PTEN as a candidate miR-155-5p target. Gain- and loss-of-function experiments and administration of a PI3K/Akt pathway inhibitor (wortmannin) were used to identify the effects of miR-155-5p and PTEN in MTT assays, flow cytometric analysis, wound healing assays and transwell assays. The results showed that miR-155-5p was highly overexpressed; however, PTEN was underexpressed in the HCC rat models, human HCC tissues and cell lines. In addition, miR-155-5p upregulation and PTEN downregulation were significantly associated with TNM stage (P < 0.05). Through in vitro experiments, we found that miR-155-5p promoted proliferation, invasion and migration, but inhibited apoptosis in HCC by directly targeting the 3'-UTR of PTEN. Western blots showed that miR-155-5p inactivated Bax and caspase-9, but activated Bcl-2 to inhibit apoptosis, and it activated MMP to promote migration and invasion via the PI3K/Akt pathway. A xenograft tumor model was used to demonstrate that miR-155-5p targets PTEN and activates the PI3K/Akt pathway in vivo as well. Our study highlighted the importance of miR-155-5p and PTEN associated with aggressive HCC both in vitro and in vivo.

A1166C polymorphism of the angiotensin II type 1 receptor gene contributes to hypertension susceptibility: evidence from a meta-analysis.

Background The angiotensin II type 1 receptor (AT1R) gene is a prime candidate for polymorphisms that could contribute to hypertension. A polymorphism in the 3' untranslated region, leading to the transversion of adenine to cytosine at position 1166, has been the most-studied variant. However, the results have been inconsistent, and we therefore performed a meta-analysis to evaluate the association of this polymorphism with hypertension. Methods We conducted an extended a computer-based literature search of PubMed and Web of Knowledge up to November 30, 2015. The extracted data were analysed statistically, and pooled odds ratios with 95% confidence intervals were calculated to assess the strengths of associations using Review Manager software (version 5.2). Results After removing 5 studies that were not consistent with the Hardy-Weinberg equilibrium, we finally collected 41 case-control studies involving 11,837 cases and 11,020 controls to evaluate the association between AT1R polymorphisms and hypertension. We found that the risk of hypertension was higher for allele C than for allele A under the codominant model, significantly higher for genotype CC + AC than for genotype AA under the dominant model, and significantly higher for genotype CC + AC in Caucasians. Conclusion This meta-analysis suggests that the AT1R 1166 CC + AC genotype consistently confers susceptibility to hypertension and that early preventive measures should be applied in clinical settings according to patient genotypes.