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Our preliminary data showed that VEGFR2 upregulation promoted renal ROS overproduction in high-fat diet- (HFD-) treated mice. Given that ROS-induced NLRP3 activation plays a central role in the pathogenesis of type 2 diabetic kidney injury, we evaluate whether VEGFR2 upregulation induces type 2 diabetic kidney injury via ROS-mediated NLRP3 activation and further explore the underlying mechanism. Our results showed that VEGFR2 knockdown decreased ROS overproduction, blocked NLRP3-dependent inflammation, and alleviated kidney damage in HFD-treated mice. Treatment with α -lipoic acid, a scavenger of ROS, lowered ROS overproduction and alleviated NLRP3-triggered kidney injury of HFD-treated mice. Collectively, the VEGFR2/ROS/NLRP3 signal is a critical therapeutic strategy for the kidney injury of HFD-treated mice. Purple sweet potato color (PSPC), a natural anthocyanin, can exert renal protection by inhibiting ROS in HFD-treated mice. Here, we provide a novel mechanism of PSPC against renal damage in HFD-treated mice by downregulating VEGFR2 expression.

Background: For patients with chronic hepatitis B and cirrhosis in less developed western regions in China, due to constraints of local economic conditions, the choice of treatment measures is often limited. However if patients recieved valid management and effective treatment, they were able to maintain their health and benign prognosis., Case Presentation: This study narrates the long-term treatment and careful follow-up of a patient with chronic hepatitis B and cirrhosis in a less developed western region in China, and analyzes the prognosis of the disease and countermeasures., Conclusions: This would partly reflect the development of antiviral therapy for chronic hepatitis B and multidisciplinary comprehensive treatment for cirrhosis-related complications in remote region with limited resources in the past 20 years.

Glioma is known to be the most prevalent primary brain tumor. In recent years, there has been evidence indicating myeloid cell leukemia-1 (MCL1) plays a role in brain glioblastoma. Therefore, the present study was conducted with aims of exploring the ability of MCL1 silencing to influence glioma cell senescence and apoptosis through the mediation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor-adjacent tissues were collected in order to detect the presence of higher levels of MCL1 protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and phosphatase and tensin homolog (PTEN) were determined. Cell counting kit-8 assay was applied to detect cell proliferation, β-galactosidase staining for cell senescence, and flow cytometry for cell cycle entry and apoptosis. Initially, the results revealed higher positive expression rate of MCL1 protein, increased mRNA and protein expression of MCL1, PI3K, Akt, Bmi-1, and Bcl-2 and decreased that of Bax and PTEN in human glioma tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein expression of PI3K, Akt, Bmi-1, and Bcl-2 and an increase in Bax and PTEN expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell proliferation and cell cycle entry in glioma cells, and promoted glioma cell senescence and apoptosis. In conclusion, the aforementioned results collectively suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the expression of MCL1 might have therapeutic functions in glioma. © 2018 IUBMB Life, 71(1):81-92, 2019., (© 2018 International Union of Biochemistry and Molecular Biology.)

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, affecting the quality of life of millions of people worldwide. The present study aims to determine the relationship between micro-RNA-143 (miR-143) and C-X-C motif chemokine 13 (CXCL13) and whether it influences the pathogenesis of myasthenia gravis (MG). Thymus specimens were resected from patients with thymic hyperplasia combined with MG and then infused into normal mouse cavities to establish MG mouse models. Immunohistochemistry, reverse transcription-quantitative PCR, in situ hybridization detection, and Western blot analysis were employed to identify the expression of miR-143 and CXCL13 in MG and normal mice. The obtained thymocytes were cultured in vitro and transfected with a series of miR-143 mimic, miR-143 inhibitor, overexpression of CXCL13, or siRNA against CXCL13. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry assays were employed to assess cell viability, cycle entry, and apoptosis of the thymocytes. Dual-luciferase reporter assay provided verification, confirming that CXCL13 was the target gene of miR-143. Low miR-143 expression in the thymus tissues of the MG mice was detected, which presented with a reciprocal relationship with the expression rate of CLCX13. Observations in relation to the interactions between miR-143 mimic or siRNA-CXCL13 exposure showed reduced cell viability, with a greater number of cells arrested at the G0/G1 phase and a greater rate of induced apoptosis. Furthermore, overexpression of CXCL13 rescued miR-143 mimic-induced apoptosis. The findings have identified the potential role of miR-143 as a MG development mediator by targeting CXCL13. The key results obtained provide a promising experimental basis for targeted intervention treatment with miR-143.

Objective: To investigate the expression levels of T follicular helper (Tfh) with different subsets in patients with rheumatoid arthritis (RA) and their serum interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) and matrix metalloproteinase 3 (MMP-3) contents., Patients and Methods: The medical records of 45 RA patients in the Department of Rheumatology and Immunology in the First Affiliated Hospital of Chengdu Medical College from January 2016 to April 2018 were retrospectively analyzed. They were divided into the RA high activity group (24 cases, group A) (DAS28 score ≥ 5.0) and RA low activity group (21 cases, group B) (3.2 < DAS28 score < 5.0). At the same time, 20 healthy subjects were selected as a control group. Flow cytometry was used to detect the expression levels of Tfh1, Tfh2 and Tfh17, enzyme-linked immunosorbent assay to detect serum IL-6, IL-17, IL-21 and MMP-3 concentrations. The correlation of Tfh cells with IL-6, IL-17, IL-21 and MMP-3 was analyzed., Results: Those of peripheral blood mononuclear cell (PBMC) Tfh2 and Tfh17 cells were significantly higher in group A than those in group B (p < 0.05). Compared with the control group, the concentrations of serum IL-6, IL-17 and MMP-3 significantly increased (p < 0.001), but that of serum TGF-β markedly decreased in group A and group B (p < 0.01). The concentrations of serum IL-6, IL-17 and MMP-3 were remarkably higher in group A than those in group B (p < 0.001), but that of serum TGF-β was significantly lower in group A than that in group B (p < 0.001). The expression level of PBMC Tfh2 cells, PBMC Tfh17 cells was positively correlated with serum IL-6, IL-17 and MMP-3. The expression levels of Tfh2 and Tfh17 cells are positively correlated with serum IL-6, IL-17 and MMP-3 concentrations, negatively correlated with serum TGF-β concentration., Conclusions: Tfh2 and Tfh17 are expected to be new targets for immunotherapy in RA patients.

Current evidence indicates that carotid atherosclerosis is an independent risk factor for cognitive impairment. Serum metabolomic analysis holds significant promise for uncovering the relationship between carotid atherosclerosis and cognitive impairment. In this study, we aimed to evaluate the profiling of serum carbonyl compounds in subclinical carotid atherosclerosis (SCA) patients and to explore the relationship between serum carbonyl compounds and cognitive performance. We enrolled 51 SCA patients and 45 healthy control individuals using carotid ultrasound assessment. All the participants were subjected to a neuropsychological assessment and their fasting serum samples were collected for untargeted stable isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis. Compared with the control, the SCA group showed lower scores in global cognition, immediate memory, verbal fluency, executive function, and visual attention. For the isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis, 149 potential carbonyl candidates were discovered in the pooled serum. In the SCA serum, 41 carbonyl compounds showed significantly increased levels and 14 carbonyl compounds showed significantly decreased levels. In addition, six carbonyl compounds involved in the oxidation of polyunsaturated fatty acids and vitamin E were correlated with cognitive performance. A negative correlation was observed between cognitive performance and the levels of octanal, nonanal, α-tocopherolquinone, and heptanal, respectively. A positive correlation was observed between cognitive performance and the levels of acetophenone and 1-(3-aminopropyl)-4-aminobutanal, respectively. In summary, the SCA individuals have poor cognitive performance, which may be reflected by aberrant serum carbonyl compound profiles.

Recent studies have proposed that microRNAs (miR) function as novel diagnostic and prognostic biomarkers and therapeutic targets in Alzheimer's disease (AD), a common disease among the elderly. In the current study, we aim to explore the effect of miR-186 on oxidative stress injury of neuron in rat models of AD with the involvement of the interleukin-2 (IL2) and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. AD rat models were established, and dual-luciferase reporter assay and online software were used to confirm the targeting relationship between miR-186 and IL2. Immunohistochemistry was used evaluating the positive rate of IL2. Afterward, to define the role of miR-186 in AD, miR-186, IL2, and JAK-STAT related protein (JAK2, STAT3) expressions were quantified. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and cell apoptosis was detected by flow cytometry. We observed downregulated miR-186 and IL2 and upregulated JAK-STAT signaling pathway related genes in AD. The overexpression of miR-186 was shown to significantly promote cell proliferation while suppressing cell apoptosis along with the expression of the IL2 and JAK-STAT signaling pathway related protein. Collectively, the key findings obtained from the current study define the potential role of miR-186 as an inhibitor of AD development by downregulation of IL2 through suppression of the JAK-STAT signaling pathway., (© 2018 Wiley Periodicals, Inc.)

Objectives: Diabetic nephropathy (DN) is a nerve damaging disorder, characterized by glomerular mesangial cell expansion and accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate mesangial cell proliferation and ECM accumulation when promoting or suppressing endogenous miR-382 in glomerular mesangial cells of DN., Materials and Methods: Model establishment consisted of DN induction by streptozotocin (STZ) in mice. The underlying regulatory mechanisms of miR-382 were analysed in concert with the treatment of miR-382 mimics, miR-382 inhibitors or siRNA against FoxO1 in cultured glomerular mesangial cells isolated from DN mice., Results: FoxO1 was identified as the downregulated gene in DN based on the microarray data of GSE1009. We found that miR-382 was significantly upregulated in renal tissues of DN mice and its downregulation dephosphorylated FoxO1, reduced glomerular mesangial cell proliferation and ECM accumulation in vitro. The determination of luciferase activity suggested that miR-382 negatively targeted FoxO1. Expectedly, distinct levels of phosphorylated FoxO1 were observed in the renal cortices of DN mice, while the silencing of FoxO1 was found to increase glomerular mesangial cell proliferation and ECM accumulation in vitro. Reduced glomerular mesangial cell proliferation and ECM accumulation elicited by miR-382 inhibitors were reversed by silencing FoxO1., Conclusions: This study demonstrates miR-382 suppression exerts a potent anti-proliferative effect that may be applied to inhibit glomerular mesangial cell proliferation and ECM accumulation in DN., (© 2018 John Wiley & Sons Ltd.)

Previous studies indicated that transforming growth factor (TGF)-β-mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF-β-mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, coculture experiments showed that TGF-β pretreatment increased the migration and invasion potential of lung cancer cells and TGF-β pretreated A549 cells increases vascular permeability. Furthermore, we found that TGF-β-mediated exosomes, as carriers of intercellular communication, regulated lung cancer invasion, and vascular permeability. Transcriptional analysis also revealed that lnc-MMP2-2 was highly enriched in TGF-β-mediated exosomes and might function by increasing the expression of matrix metalloproteinase (MMP)2 through its enhancer activity, with ectopic expression and silencing of lnc-MMP2-2 affecting lung cancer invasion and vascular permeability. Additionally, lnc-MMP2-2 and MMP2 expression was assessed semiquantitatively, and tissue-specific correlations between lnc-MMP2-2 and MMP2 expression were evaluated. These results suggested that exosomal lnc-MMP2-2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Caffeine is contained within many drinks and food that are consumed daily. Prenatal caffeine ingestion (PCI) is a risk factor for intrauterine growth retardation (IUGR). We previously observed that PCI inhibits scavenger receptor class B type I (SR-BI)-mediated cholesterol uptake in fetal adrenals, subsequently decreasing glucocorticoid synthesis and inducing IUGR. In the present study, we aimed to investigate the long-term effects of PCI on adrenal glucocorticoid synthesis in adult male offspring rats. After establishing the PCI-induced IUGR, adult male offspring was injected intraperitoneally with 5 mg/kg·d lipopolysaccharide (LPS) for 2 days to induce acute stress. We observed persistent inhibition of SR-BI expression in PCI adrenals before and after stress. Compared with the controls, the PCI offspring had higher corticosterone concentrations after stress. The serum cholesterol concentration was stable without intergroup differences before and after stress. The cholesterol concentration in PCI adrenals showed a higher decrease rate than that of the control after stress. In summary, PCI induced long-term alterations in SR-BI expression and glucocorticoid synthesis in adult male offspring rat adrenals. Cholesterol has to be over-consumed in PCI adrenals against acute stress. This study provides an experimental basis to explain the susceptibility of IUGR offspring to metabolic diseases in adults., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study was designed to explore the relationship between miR-1275 and SERPINE1 and its effects on glioma cell proliferation, migration, invasion and apoptosis. Differentially expressed miRNAs and mRNAs in glioma tissues were screened out by bioinformatic analysis. Dual-luciferase reporter gene assay was used to validate the targeted relationship between miR-1275 and SERPINE1. qRT-PCR was used to detect the expression of miR-1275 and SERPINE1 in glioma tissues. The expressions of SERPINE1 and p53 pathway-related proteins in glioma cells were detected by western blot. Glioma cell proliferation, apoptosis, migration and invasion were respectively detected by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Tumour xenograft model was developed to study the influence of miR-1275 and SERPINE1 on glioma growth in vivo. The results of microarray analysis, qRT-PCR and western blot showed that miR-1275 was low-expressed while SERPINE1 was high-expressed in glioma. Dual-luciferase assay showed that miR-1275 could bind to SERPINE1. Overexpression of miR-1275 could promote the p53 pathway-related proteins' expression. Highly expressed miR-1275 could repress the migration, proliferation and invasion of glioma cells while highly expressed SERPINE1 had inverse effects. Tumour xenograft showed that up-regulated miR-1275 or down-regulated SERPINE1 could repress glioma growth in vivo. Up-regulation of miR-1275 activated p53 signalling pathway via regulating SERPINE1 and therefore suppressed glioma cell proliferation, invasion and migration, whereas promoted cell apoptosis., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

In the current study, we were interested in exploring the molecular mechanism of circular RNA DLEU2 (circRNA-DLEU2) (hsa&#95;circ&#95;0000488) and microRNA 496 (miR-496), as well as PRKACB, in human acute myeloid leukemia (AML) cell activities. The RNA expression levels of circRNA-DLEU2, hsa-miR-496, and PRKACB were assessed by quantitative real-time PCR (qRT-PCR). The proliferation and apoptosis abilities of the cells were determined by CCK8 assay and flow cytometry analysis. Target relationships between circRNA-DLEU2 and miR-496, as well as PRKACB, were analyzed by luciferase reporter assay and probe assay. Immunoblotting assays were used to detect the protein expression level of PRKACB. We also did in vivo experiments to observe tumor formation after overexpression of circRNA-DLEU2. Our data showed that circRNA-DLEU2 was upregulated in AML tissues and cells, which promoted AML cell proliferation and inhibited cell apoptosis. circRNA-DLEU2 promoted AML tumor formation in vivo miR-496 was inhibited by circRNA-DLEU2 and was downregulated in AML tissues. circRNA-DLEU2 inhibited miR-496 expression and promoted PRKACB expression. miR-496 antagonized the effects of PRKACB on MOLM-13 cell proliferation and apoptosis. Collectively, circRNA-DLEU2 accelerated human AML by suppressing miR-496 and promoting PRKACB expression., (Copyright © 2018 American Society for Microbiology.)

Over the past decade, lncRNAs have been widely reported in human malignant tumors, including papillary thyroid carcinoma. LncRNA SNHG15 has been validated to be a tumor facilitator in several types of malignancies. The present study focused on the biological role of SNHG15 in papillary thyroid carcinoma. Based on the result of qPCR analysis, we identified the strong expression of SNHG15 in human papillary thyroid carcinoma tissues and cell lines. Moreover, Kaplan-Meier method was utilized to analyze the internal relevance between SNHG15 expression and overall survival rate of patients with papillary thyroid carcinoma. Loss-of-function assays were designed and conducted to determine the inhibitory effects of silenced SNHG15 on the cell growth and migration in papillary thyroid carcinoma. The mechanical investigation indicated that SNHG15 upregulated YAP1 by sponging miR-200a-3p. Moreover, results of gain-of-function assays validated the anti-oncogenic function of miR-200a-3p in papillary thyroid carcinoma. Finally, results of rescue assays validated the function of SNHG15-miR-200a-3p-YAP1 axis in papillary thyroid carcinoma. YAP1 is known as an oncogene and a core factor of Hippo pathway. Here, we demonstrated that SNHG15 inactivated Hippo signaling pathway in papillary thyroid carcinoma. In summary, our findings demonstrated that SNHG15 serves as a competitively endogenous RNA (ceRNA) to regulate YAP1-Hippo signaling pathway by sponging miR-200a-3p in papillary thyroid carcinoma.

The loss of pancreatic islet β-cell function represents the classical feature in the pathogenesis of type 2 diabetes mellitus (T2DM). Previous evidence has highlighted the involvement of the activated JNK pathway in relation to islet β-cell apoptosis. Hence, during the present study a streptozotocin-induced DM mice model was established in a bid to ascertain as to whether microRNA-30d (miR-30d) plays a regulatory role in the JNK pathway in relation to islet β-cell dysfunction. The collection and identification of the islet β cells from streptozotocin-induced mice was performed. Islet β cells with elevated or suppressed levels of miR-30 as well as knocked down SOCS3 were established in order to verify the regulatory mechanisms by which miR-30d governs SOCS3 in vitro. We found miR-30d was overexpressed among tissue samples obtained form streptozotocin-induced mice and their islet β cells, as well as increasing miR-30d expression when the JNK pathway was activated were found to promote islet β cell growth and cell cycle entry, and inhibit apoptosis. SOCS3, confirmed to be a miR-30d target, was decreased in the islet β cells following the promotion of miR-30d, while the JNK pathway was inhibited following SOCS3 knocdown. Furthermore, the effect of miR-30d inhibition was lost in islet β cells when SOCS3 was knocked down. The data of the present study support the notion that miR-30d-mediated direct suppression of SOCS3 acts to protect pancreatic β-cell functions through the JNK signaling pathway, emphasizing the potential of miR-30d as a novel pharmacological target for treatment and intervention of DM., (© 2018 Wiley Periodicals, Inc.)

Epilepsy is a group of neurological disorders characterized by epileptic seizures. In this study, we aim to explore the role of microRNA-421 (miR-421) in hippocampal neurons of epilepsy mice via the TLR/MYD88 pathway. Forty mice were randomly served as the normal and model (established as epilepsy model) groups. Hippocampal neurons were assigned into seven groups with different transfections. The RT-qPCR and western blotting were conducted to examine the expression of miR-421 TLR2, TLR4, MYD88, Bax, Bcl-2, p53, Beclin-1, and LC3II/LC3I. Cell proliferation and apoptosis were detected by MTT and flow cytometry.MYD88 is a target gene of miR-421. Model mice showed elevated expression of TLR2, TLR4, MYD88, Bax, p53, Beclin-1, and LC3II/LC3I but reduced expression of miR-421 and Bcl-2. In vitro experiments reveals that overexpression of miR-421 inhibited the TLR/MYD88 pathway. Besides, overexpressed miR-421 declined cell apoptosis but increased cell proliferation. It reveals that miR-421 targeting MYD88 could inhibit the apoptosis and autophagy of hippocampal neurons in epilepsy mice by down-regulating the TLR/MYD88 pathway., (© 2018 Wiley Periodicals, Inc.)

The present study was to investigate the effect of lncRNA LINC00880 targeting CACNG5 on cell proliferation, migration, invasion, and apoptosis in spinal cord ependymoma (SCE) through the MAPK signaling pathway. GEO database was used to download gene expression data related with SCE (GSE50161 and GSE66354) and annotation file. LncRNA with differential expression was predicted by Multi Experiment Matrix website (MEM). The target gene was analyzed by KEGG pathway enrichment analysis. SCE tissues and adjacent tissues were collected. The positive expression of CACNG5 protein was tested by immunohistochemistry. Expression of LINC00880, CACNG5, and MAPK signaling pathway-related proteins was measured with qRT-PCR and Western blotting. Cell proliferation, migration, invasion, cycle, and apoptosis were detected using MTT, Transwell assay, Scratch test, and Flow cytometry. SCE tissues showed increased LINC00880 expression. CACNG5 was a target gene of LINC00880 and correlated with MAPK signaling pathway. Compared with adjacent tissues, SCE tissues showed lower positive expression of CACNG5. Compared with the blank group, LINC00880 expression was higher in the LINC00880 vector and LINC00880 vector + CACNG5 vector groups, and lower in the si-LINC00880 and si-LINC00880 + si-CACNG5 groups; in the LINC00880 vector and si-CACNG5 groups, expression of survivin, p38MAPK, ERK1/2, JNK1/2/3 increased and CACNG5 and Bax expression reduced, the proliferation, invasion and migration of tumor cells increased, and apoptosis rate decreased. Opposite results were found in the si-LINC00880 and CACNG5 vector groups. The findings indicate that lncRNA LINC00880 targeting CACNG5 inhibits cell apoptosis and promotes proliferation, migration, and invasion in SCE through the MAPK signaling pathway., (© 2017 Wiley Periodicals, Inc.)

MicroRNAs (miRNAs), a novel class of important gene-regulatory molecules, correlates with tumor growth, invasion, metastasis, and chemo resistance in gastric cancer (GC). Microarray analysis revealed that aberrant expressed microRNA-17 (miR-17) and DEDD were identified in GC. DEDD has been found to act as an endogenous suppressor of tumor growth and metastasis through epithelial-mesenchymal transition (EMT) process. However, the role of miRNA-17 (miR-17) has not been clearly evaluated in GC, thereby a series of in vitro experiments were performed in this study. The levels of miR-17 and DEDD in GC tissues from patients diagnosed with GC and in five GC cell lines (SGC-7901, MKN-45, HGC-27, BGC823, and AGS) were detected. It was found that miR-17 up-regulated and DEDD down-regulated in GC, and SGC-7901 and AGS cells were adopted for the in vitro cell experiments, in which the expression of miR-17 or DEDD was regulated by transfection. DEDD was validated to be a target gene of miR-17. Inhibition of miR-17 impaired EMT in GC cells. In addition, transwell assay and scratch test results revealed that inhibition of miR-17 hindered GC cell invasion and migration. Moreover, inhibition of miR-17 reduced resistance to cisplatin- or 5-Fu in GC cells and induced cisplatin- or 5-Fu-treated GC cell apoptosis, which evaluated by using CCK-8 and flow cytometry assays. From the short review above, the key findings emerge that inhibition of miR-17 may have tumor suppressive effects on GC and enhance its chemosensitivity by promoting DEDD, highlighting a novel target for GC therapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study aims to investigate the effect of microRNA-129 (miR-129) on proliferation and apoptosis of hippocampal neurons in epilepsy rats by targeting c-Fos via the MAPK signaling pathway. Thirty rats were equally classified into a model group (successfully established as chronic epilepsy models) and a normal group. Expression of miR-129, c-Fos, bax, and MAPK was detected by RT-qPCR and Western blotting. Hippocampal neurons were assigned into normal, blank, negative control (NC), miR-129 mimic, miR-129 inhibitor, siRNA-c-Fos, miR-129 inhibitor+siRNA-c-Fos groups. The targeting relationship between miR-129 and c-Fos was predicted and verified by bioinformatics websites and dual-luciferase reporter gene assay. Cell proliferation after transfection was measured by MTT assay, and cell cycle and apoptosis by flow cytometry. c-Fos is a potential target gene of miR-129. Compared with the normal group, the other six groups showed a decreased miR-129 expression; increased expression of expression of c-Fos, Bax, and MAPK; decreased proliferation; accelerated apoptosis; more cells arrested in the G1 phase; and fewer cells arrested in the S phase. Compared with the blank and NC groups, the miR-129 mimic group and the siRNA-c-Fos group showed decreased expression of c-Fos, Bax, and MAPK, increased cells proliferation, and decreased cell apoptosis, fewer cells arrested in the G1 phase and more cells arrested in the S phase. However, the miR-129 inhibitor groups showed reverse consequences. This study suggests that miR-129 could inhibit the occurrence and development of epilepsy by repressing c-Fos expression through inhibiting the MAPK signaling pathway., (© 2017 Wiley Periodicals, Inc.)

Purpose: Gastric cancer is mainly treated by gastrectomy, the results of which were unsatisfactory without any adjuvant treatments. This study aimed to examine the performance of radiotherapy, chemotherapy, and chemoradiotherapy after surgery in order to acquire the optimal adjuvant treatment. Method: Embase and PubMed were retrieved to conduct a systematic research. Hazard ratios (HR) of overall survival (OS) and progression-free survival (PFS) as outcomes were calculated by synthesizing direct and indirect evidence to evaluate the efficacy of three treatments against surgery alone. The P -score ranking was utilized to rank the therapies. Consistency was assessed by heat plot. Begg's test was performed to evaluate publication bias. Results: A total of 35 randomized controlled studies (RCTs) with 8973 patients were included in our network meta-analysis (NMA). As for efficacy outcomes, OS and PFS of 1, 2, 3, and 5 years, all revealed chemoradiotherapy (CRT) as the best of three adjuvant therapies. Meanwhile, P -score ranking results also displayed that CRT was the optimal regimen. Additionally, radiotherapy (RT) and chemotherapy (CT) were two alternative options following CRT since RT performed well in short-term survival while CT could improve the long-term survival. Conclusion: CRT was the most recommended therapy to accompany surgery according to our results. However, no analysis about the safety of these three treatments was mentioned in our study. Further studies including safety outcomes were required to draw a more comprehensive conclusion.

Graves' disease is an autoimmune process in which the thyroid gland is triggered by autoantibodies, resulting in hyperthyroidism. The purpose of the present study is to elucidate whether exon-1 49 A/G and promoter region 318C/T polymorphisms in the CTLA-4 gene. This study consisted of 653 eligible patients with Graves' disease. After receiving 131I radionuclide therapy, these patients were classified into the remission and non-remission groups. A logistic regression-based model was used to analyze independent factors affecting the patient response to 131I radionuclide therapy. The results showed that CTLA-4 49 A/G was closely related to the efficacy of 131 I treatment for Graves' disease (AG + GG vs. AA: OR = 6.543, 95%CI = 2.611 ∼ 16.40, P < 0.001; G vs. A: OR = 3.482, 95%CI = 2.457 ∼ 4.934, P < 0.001). Moreover, the findings revealed that haplotype A-C (P < 0.001, OR = 3.592, 95%CI: 2.451 ∼ 5.262) and G-C (P < 0.001, OR = 0.282, 95%CI: 0.204 ∼ 0.391) were associated with the efficacy of 131 I therapy in treating Graves' disease. Logistic regression analysis indicated that thyroid weight (OR = 0.963, 95%CI = 0.944 ∼ 0.982, P < 0.001) and CTLA-4 exon-1 49 A/G polymorphism (OR = 0.334, 95%CI = 0.233 ∼ 0.478, P < 0.001) independently affect the efficacy of 131 I therapy in Graves' disease. These data indicated that CTLA-4 exon-1 49 A/G polymorphism may be associated with patient response to radionuclide 131 I therapy in Graves' disease., (© 2017 Wiley Periodicals, Inc.)

Sixty novel allogibberic acid derivatives containing 1,2,3-triazole pharmacophore were designed and synthesized. The key chemical processes include aromatization of the A ring in gibberellins, formation of allogibberic azides and its copper mediated Huisgen 1,3-dipolar cycloaddition with alkynes. A number of hybrids containing α,β-unsaturated ketone moiety exhibited excellent in vitro cytotoxic activities. Some of the hybrids were more selective to MCF-7 and SW480 cell lines with IC 50 values at least 8-fold more cytotoxic than cisplatin (DDP). The most potent compounds C43 and C45 are more cytotoxic than cisplatin (DDP) against all tested five tumor cell lines, with IC 50 values of 0.25-1.72 µM. Mechanism of action studies indicated that allogibberic-triazole derivative C45 could induce the S phase cell cycle arrest and apoptosis in SMMC-7721 cell lines., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study investigates the protective effects of miR-431 against cerebral ischemia-reperfusion injury through the Rho/Rho-kinase signaling pathway. SD rats were randomly classified into normal, sham, and model (middle cerebral artery occluded) groups. Rho expression and cerebral infarction were visualized by immunohischemistry and TTC staining, respectively. qRT-PCR and western blotting were used to measure mRNA and protein expression of miR-431 and Rho/Rho-kinase signaling pathway-related genes. Hippocampal neurons were extracted and assigned into normal, blank, negative control (NC), miR-431 mimics, miR-431 inhibitors, siRNA-Rho, and miR-431 inhibitors + siRNA-Rho groups. Proliferation and apoptosis were detected by MTT and flow cytometry, respectively. Compared with the normal group, the model group showed elevated Rho expression, area of cerebral infarction, and expressions of Rho/Rho-kinase related genes but reduced miR-431 expression. Compared with the blank group, expression of Rho, Rho-kinase α, and Rho-kinase β decreased and miR-431 expression increased in the miR-431 mimics and siRNA-Rho groups, and the tendency reversed in the miR-431 inhibitors group. Enhanced proliferation and inhibited apoptosis were exhibited in the miR-431 mimics and siRNA-Rho groups while results in the miR-431 inhibitors group reversed. Findings obtained from this study indicated that miR-431 confers protection against cerebral ischemia-reperfusion injury through negatively regulating the Rho/Rho-kinase signaling pathway., (© 2017 Wiley Periodicals, Inc.)

Diabetes often causes learning and memory deficits, which leads to unfavorable behavioral performance. In this study, we investigated the effects of long non-coding RNA (lncRNA) ANRIL on learning, memory abilities, and hippocampal neuronal apoptosis via the NF-κB signaling pathway in streptozotocin (STZ)-induced diabetic rats. After successful establishment of diabetic rat models, the subjects were then assigned into the DM, DM + si-ANRIL, DM + si-negative control (si-NC) groups, as well as an additional normal group. Morris water maze test was employed to assess behavioral performance of rats, followed by the recording of body weight and blood glucose levels. Expressions of ANRIL, NF-κB signaling pathway-related, and apoptosis-related genes were examined by qRT-PCR and western blotting. Rat hippocampus expression levels of cleaved-caspase-3 were determined by immunofluorescence. Cell apoptosis was examined by TUNEL assay. Versus to the normal group, revealed there to be activation of the NF-κB signaling pathway, decreased weight, increased blood glucose, increased escape latency, reduced residence time, memory impairment, increased cleaved-caspase-3 expression, and increased apoptosis were detected in the DM and DM + si-NC groups. The DM + si-ANRIL group exhibited inhibited NF-κB signaling pathway, weight loss, decreased blood glucose, recovered memory, decreased cleaved-caspase-3 expression and reduced apoptosis compared to the DM group, with higher weight of rats, lower blood glucose levels, and stronger memory abilities in the DM + si-ANRIL group. Taken together, these findings indicate that silencing lncRNA ANRIL promotes memory recovery and decreases hippocampal neurons apoptosis in diabetic rats through the inhibition of the NF-κB signaling pathway., (© 2018 Wiley Periodicals, Inc.)

Hypoxia-ischaemia (HI) remains a major cause of foetal brain damage presented a scarcity of effective therapeutic approaches. Dexmedetomidine (DEX) and microRNA-140-5p (miR-140-5p) have been highlighted due to its potentially significant role in the treatment of cerebral ischaemia. This study was to investigate the role by which miR-140-5p provides cerebral protection using DEX to treat hypoxic-ischaemic brain damage (HIBD) in neonatal rats via the Wnt/β-catenin signalling pathway. The HIBD rat models were established and allocated into various groups with different treatment plans, and eight SD rats into sham group. The learning and memory ability of the rats was assessed. Apoptosis and pathological changes in the hippocampus CA1 region and expressions of the related genes of the Wnt/β-catenin signalling pathway as well as the genes responsible of apoptosis were detected. Compared with the sham group, the parameters of weight, length growth, weight ratio between hemispheres, the rate of reaching standard, as well as Bcl-2 expressions, were all increased. Furthermore, observations of increased levels of cerebral infarction volume, total mortality rate, response times, total response duration, expressions of Wnt1, β-catenin, TCF-4, E-cadherin, apoptosis rate of neurons, and Bax expression were elevated. Following DEX treatment, the symptoms exhibited by HIBD rats were ameliorated. miR-140-5p and si-Wnt1 were noted to attenuate the progression of HIBD. Our study demonstrates that miR-140-5p promotes the cerebral protective effects of DEX against HIBD in neonatal rats by targeting the Wnt1 gene through via the negative regulation of the Wnt/β-catenin signalling pathway., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

In this study, we aim to investigate the role of tanshinone IIA in myocardial infarction (MI), especially in left ventricular remodelling (VR) and the underlying mechanism involving the TLR4/MyD88/NF-κB signalling pathway. Sprague-Dawley (SD) rats (n = 96) were selected, and 12 of them underwent sham surgery. The remaining 84 rats were subjected to MI modelling. HE and MT staining were carried out to estimate infract size, histopathological changes and fibrosis degree. Macrophage infiltration and cardiomyocyte apoptosis were evaluated by immunohistochemistry and TUNEL staining. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to determine the expression levels of TLR4, MyD88 and NF-κB. Serum levels of IL-2, IL-6, IL-8, TNF-a, procollagen I Cpropeptide (PICP), and procollagen III N-propeptide (PIIINP) were measured using enzyme-linked immunosorbent assay (ELISA). The heart weight/body weight, mean arterial pressure (MAP), left ventricular end-systolic pressure (LVESP), +dP/dt and -dP/dt increased while the ventricular function and the left ventricular end-diastole pressure (LVEDP) decreased in MI rats. Compared with the rats undergoing sham surgery, MI rats showed larger infarct size, severer fibrosis, higher expression levels of TLR4, NF-κB-P65, MyD88, IL-2, IL-6, IL-8, TNF-a, PICP and PIIINP as well as enhanced macrophage infiltration, cardiomyocyte apoptosis. After treatment with tanshinone IIA combined with LPS for 4 weeks, the rats showed better condition than those treated with only LPS. These results indicate that tanshinone IIA attenuates MI and prevents left VR. Importantly, inhibition of TLR4/MyD88/NF-κB signalling pathway is a key step in this process., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: As a form of dementia primarily affecting the elderly, vascular dementia (VD) is characterized by changes in the supply of blood to the brain, resulting in cognitive impairment. The aim of the present study was to explore the effects involved with cyclic adenosine monophosphate (cAMP) response element-binding (CREB)1 gene silencing on cognitive dysfunction through meditation of the protein kinase A (PKA)-CREB signaling pathway in mice with VD., Methods: Both the Morris water maze test and the step down test were applied to assess the cognitive function of the mice with VD. Immunohistochemical and TUNEL staining techniques were employed to evaluate the positive expression rates of the protein CREB1 and Cleaved Caspase-3, as well as neuronal apoptosis among hippocampal tissues in a respective manner. Flow cytometry was applied to determine the proliferation index and apoptosis rate of the hippocampal cells among each group. Reverse transcription quantitative polymerase chain reaction and Western blot analysis methods were applied to detect the expressions of cAMP, PKA and CREB in hippocampal cells., Results: Compared with the normal group, all the other groups exhibited impaired cognitive function, reduced cell numbers in the CAI area, positive expressions of CREB1 as well as positive optical density (OD) values. Furthermore, increased Cleaved Caspase-3 positive expression, OD value, proliferation index, apoptosis rate of hippocampal cells and neurons, were observed in the other groups when compared with the normal group, as well as lower expressions of cAMP, PKA and CREB1 and p-CREB1 (the shCREB1-1, H89 and shCREB1-1 + H89 groups < the VD group)., Conclusion: The key findings of the present study demonstrated that CREB1 gene silencing results in aggravated VD that occurs as a result of inhibiting the PKA-CREB signaling pathway, thus exasperating cognitive dysfunction.

A hydroponic experiment was conducted to investigate the effects of oxalic acid (OA) on arsenic (As) uptake and the physiological responses of Hydrilla verticillata exposed to 3 mg L -1 of As in different forms. Plant As(III) uptake was significantly increased by 200-2000 µg L -1 OA. However, an increase of As(V) uptake was only shown with 1000 µg L -1 OA, and no significant difference was observed with dimethylarsinate treatment. Peroxidase and catalase activities, and the contents of photosynthetic pigments, soluble sugar and proline, were significantly increased by 1000 µg L -1 OA during As(III) treatment. Superoxide dismutase and proline were also increased significantly by 1000 µg L -1 OA when plants were exposed to As(V). In DMA treatment, proline was significantly increased by 500 µg L -1 OA. Therefore, As-induced oxidative stress is relieved by OA, but it depends on OA concentration and the form of As. Our results may be useful for the phytoremediation of waste water containing As and OA.

Background: Health education (HE) courses in schools are vital paths for improving teenagers' health literacy. HE and physical education (PE) teachers lead HE courses, and their teaching intentions and competency influence the effectiveness of the courses and the ability to promote students' health literacy. This study attempted to understand HE and PE teachers' health literacy teaching intentions and professional competency and to investigate their relationships., Methods: This study adopted a cross-sectional design. A questionnaire survey was administered to 906 middle school HE and PE teachers in Taiwan by mail, and 545 provided valid data with consent., Results: Participants had a favorable health literacy (47.78/50), positive health literacy teaching beliefs and attitudes, and acceptable efficacy. They intended to implement health literacy instruction within the subsequent year. Teaching beliefs, attitudes, and efficacy were all positively correlated with intentions (all p < .001). Demographic variables, health literacy, and teaching beliefs, attitudes, and efficacy explained 33.5% of the variance of teaching intentions., Conclusion: Teaching beliefs, attitudes, and efficacy were crucial predictors of health literacy teaching intentions. To improve students' health literacy, educational authorities and schools should pay attention to HE and PE teachers' intentions and vital factors, thereby enhancing teachers' willingness to perform health literacy instruction., (© 2018, American School Health Association.)

We explored the effect of S100A12 gene on serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by activating the extracellular signal-regulated kinase (ERK) signaling pathway. A total of 180 specific pathogen-free (SPF) rats were purchased to establish cecal ligation and puncture (CLP) model. Rats were assigned into the sham, model, empty vector, S100A12 siRNA, epidermal growth factor (EGF), and S100A12 siRNA + EGF groups. The expressions of S100A12, ERK-1, ERK-2, cPLA2, and NF-κB in liver tissues of rats among six groups were detected by RT-qPCR and western blotting. ELISA was used to determine serum levels of IL-1β, IL-10, TNF-α, procalcitonin (PCT), and C-reactive protein (CRP). Pearson correlation analysis was conducted to measure correlations. Cell apoptosis of rats among six groups was detected by Tunel staining. The expressions of S100A12, ERK-1, ERK-2, cPLA2, and NF-κB decreased in the S100A12 siRNA group while increased in the EGF group compared with the model group. S100A12 mRNA expression was positively correlated with mRNA expressions of related genes in the ERK signaling pathway (ERK-1, ERK-2, cPLA2, and NF-κB) in the model and empty vector groups. Expressions of IL-1β, IL-6, TNF-α, PCT, and CRP in the EGF group were higher than those in the model group, but were lower than those in the S100A12 siRNA group. Compared with the model group, cell apoptosis decreased in the S100A12 siRNA group but that increased in the EGF group. We demonstrates that S100A12 gene silencing decreases serum levels of anti-inflammatory/pro-inflammatory cytokines in septic rats by inhibiting the ERK signaling pathway., (© 2018 Wiley Periodicals, Inc.)

Aims: Several microRNAs (miRs) are expressed aberrantly and associated with progression, tumorigenesis, and prognosis of haematological and solid tumors. The study aimed to identify the effects involved with microRNA-136 (miR-136) on the concurrent enhancement of proliferation, apoptosis and radiosensitivity of cervical carcinoma through the NF-κB signaling pathway by targeting E2F1., Main Methods: Totally 338 patients with cervical carcinoma were recruited in this study. The expressions of miR-136, E2F1, p65, CyclinD1, Atm, Chk2, Bcl-2, Survivin and Bax were detected using RT-qPCR and Western blot analysis. Cells with highest miR-136 expression were subsequently assigned into different groups. Cell survival and apoptosis rate were detected by colony formation assay and flow cytometry, respectively., Key Findings: Compared to the sensitivity group, E2F1, p65, Bcl-2 and Survivin exhibited increased levels, while expression of CyclinD1, Atm, Chk2, Bax and miR-136 was reduced in the confrontation group. Cell survival rate was declined at 6 and 8 Gy of X-ray irradiation compared with 0, 2 and 4 Gy. Compared with the blank and NC groups, expression of E2F1, p65, Bcl-2 and Survivin was increased, while that of CyclinD1, Atm, Chk2, Bax and miR-136 was all decreased. The cell survival rate was increased; while apoptosis rate was decreased in the miR-136 inhibitor group. The trends observed in the miR-136 mimics and siRNA-E2F1 groups were contradictory to the miR-136 inhibitor group., Significance: Based on our results, miR-136 inhibits proliferation, while acting to promote apoptosis and radiosensitivity in cervical carcinoma by targeting E2F1 through the NF-κB signaling pathway, resulting in improved prognoses., (Copyright © 2018. Published by Elsevier Inc.)

Evidence indicates that oxidative stress is the central pathological feature of 2, 2´, 4, 4´-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity. Protein kinase C delta (PKCδ), an oxidative stress-sensitive kinase, can be proteolytically cleaved to yield a catalytically active fragment (PKCδ-CF) that is involved in various neurodegenerative disorders. Here, we showed that BDE-47 treatment increased ROS, malondialdehyde, and protein carbonyl levels in the mouse hippocampus. In turn, excessive ROS induced caspase-3-dependent PKCδ activation and stimulated NF-κB p65 nuclear translocation, resulting in inflammation in the mouse hippocampus. These changes caused learning and memory deficits in BDE-47-treated mice. Treatment with Z-DEVD-fmk, a caspase-3 inhibitor, or N-acetyl-L-cysteine, an antioxidant, blocked PKCδ activation and subsequently inhibited inflammation, thereby improving learning and memory deficits in BDE-47-treated mice. Our data further showed that activation of ROS-PKCδ signaling was associated with DJ-1 downregulation, which exerted neuroprotective effects against oxidative stress induced by different neurotoxic agents. Adeno-associated viral vector-mediated DJ-1 overexpression in the hippocampus effectively inhibited excessive ROS production, suppressed caspase-3-dependent PKCδ cleavage, blunted inflammation and ultimately reversed learning and memory deficits in BDE-47-treated mice. Taken together, our results demonstrate that DJ-1 plays a pivotal role in BDE-47-induced neurotoxic effects and learning and memory deficits., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study aims to explore whether microRNA-381 (miR-381) mediating CXCR4 affects the renal tubular epithelial cells (RTEC) of renal ischemia reperfusion (I/R) injury. Forty-eight rats were assigned into the I/R (n = 24, successfully established as I/R model) and sham (n = 24) groups. After collecting kidney tissues, immunohistochemistry, and microvascular density (MVD) counting were conducted for CXCR4 positive expression and MVD numbers. RTECs were assigned into the sham, blank, negative control (NC), miR-381 mimics, miR-381 inhibitor, si-CXCR4, and miR-381 inhibitor + si-CXCR4 groups. RT-qPCR and Western blotting were performed for relative expressions in tissues and cells. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry. Results showed that compared with the sham group, positive expression of CXCR4 and MVD number were higher in the I/R group, which exhibited decreased miR-381 and increased expression of CXCR4, stromal cell-derived factor-1 (SDF1), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1α) and Tie-2. Dual luciferase reporter gene assay verified that CXCR4 is a target gene of miR-381. MiR-381 expression was lower in the miR-381 inhibitor + si-CXCR4 and miR-381 inhibitor groups and higher in the miR-381 mimics group than the blank and NC groups. Compared with the blank and NC groups, the miR-381 mimics and si-CXCR4 groups exhibited higher cell proliferation but lower cell apoptosis and expression of CXCR4, SDF1, VEGF, HIF-1α, and Tie-2, whereas the miR-381 inhibitor group exhibited the opposite trend. In conclusion, miR-381 may promote RTEC proliferation in rats with renal I/R injury by down-regulating CXCR4., (© 2017 Wiley Periodicals, Inc.)

The study aimed to investigate whether S100A9 gene silencing mediating the IL-17 pathway affected the release of pro-inflammatory cytokines in acute pancreatitis (AP). Kunming mice were assigned to the normal, AP, AP + negative control (NC), AP + shRNA, AP + IgG and AP + anti IL-17 groups. ELISA was applied to measure expressions of AMY, LDH, CRP, TNF-α, IL-6 and IL-8. The cells were distributed into the control, blank, NC, shRNA1 and shRNA2 groups. MTT assay, flow cytometry, RT-qPCR and Western blotting were used to evaluate cell proliferation, cell cycle and apoptosis, and expressions of S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12 in tissues and cells. Compared with the normal group, the AP group displayed increased expressions of AMY, LDH, CRP, TNFα, IL-6, IL-8, S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12. The AP + shRNA and AP + anti IL-17 groups exhibited an opposite trend. The in vivo results: Compare with the control group, the blank, NC, shRNA1 and shRNA2 groups demonstrated increased expressions of S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12, as well as cell apoptosis and cells at the G1 phase, with reduced proliferation. Compared with the blank and NC groups, the shRNA1 and shRNA2 groups had declined expressions of S100A9, TLR4, RAGE, IL-17, HMGB1 and S100A12, as well as cell apoptosis and cells at the G1 phase, with elevated proliferation. The results indicated that S100A9 gene silencing suppressed the release of pro-inflammatory cytokines through blocking of the IL-17 pathway in AP., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Previous studies suggested that lower vitamin D might be a risk factor for autism spectrum disorders (ASDs). The aim of this study was to estimate the prevalence of ASDs in 3-year-old Chinese children and to examine the association between neonatal vitamin D status and risk of ASDs. We conducted a study of live births who had taken part in expanded newborn screening (NBS), with outpatient follow-up when the children 3-year old. The children were confirmed for ASDs in outpatient by the Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria. Intellectual disability (ID) status was defined by the intelligence quotient (IQ < 80) for all the participants. The study design included a 1:4 case to control design. The concentration of 25-hydroxyvitamin D3 [25(OH)D3] in children with ASD and controls were assessed from neonatal dried blood samples. A total of 310 children were diagnosed as having ASDs; thus, the prevalence was 1.11% (95% CI, 0.99% to 1.23%). The concentration of 25(OH)D3 in 310 ASD and 1240 controls were assessed. The median 25(OH)D3 level was significantly lower in children with ASD as compared to controls (p < 0.0001). Compared with the fourth quartiles, the relative risk (RR) of ASDs was significantly increased for neonates in each of the three lower quartiles of the distribution of 25(OH)D3, and increased risk of ASDs by 260% (RR for lowest quartile: 3.6; 95% CI, 1.8 to 7.2; p < 0.001), 150% (RR for second quartile: 2.5; 95% CI, 1.4 to 3.5; p = 0.024), and 90% (RR for third quartile: 1.9; 95% CI, 1.1 to 3.3; p = 0.08), respectively. Furthermore, the nonlinear nature of the ID-risk relationship was more prominent when the data were assessed in deciles. This model predicted the lowest relative risk of ID in the 72rd percentile (corresponding to 48.1 nmol/L of 25(OH)D3). Neonatal vitamin D status was significantly associated with the risk of ASDs and intellectual disability. The nature of those relationships was nonlinear. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Objective: MicroRNAs are widely thought to play a regulatory role in gene expression. Although the more unique microRNA expression profiles have been reported in several tumors, there remains a scarcity of knowledge in relation to microRNA expression profiles in GISTs. During this study, through the alteration in the expression of microRNA-152 (miR-152) in gastrointestinal stromal tumor (GIST) cells, we subsequently evaluated its ability to influence the processes associated with cancer, including proliferation, migration, invasion, and apoptosis, as well as the associated mechanisms., Methods: The expression of miR-152 and cathepsin L (CTSL) in GIST cell lines (GIST882, GIST430, GIST48 and GIST-T1) and normal gastric mucosal cell line RGM-1 were determined. A series of miR-152 mimics, miR-152 inhibitors, and siRNA against CTSL were introduced to treat GIST-T1 cells with the lowest miR-152 and the highest CTSL were assessed. Cell viability, cell cycle entry, apoptosis, and cell migration/invasion were all evaluated by means of CCK-8 assay, flow cytometry analyses of Annexin V-FITC/PI staining, and transwell assays., Results: The target prediction program and luciferase reporter gene assay verified CTSL is the target of miR-152. Regarding the biological significance of miR-152, siRNA knockdown and ectopic expression studies revealed that miR-152 mimic or siRNA against CTSL exposure reduced cell viability and migration/invasion, which resulted in more cells arrested at the S stage, and induced apoptosis. MiR-152 inhibitor exposure was observed to have induced effects on CTSL cells as opposed to those induced by that of the miR-152 mimics. In contrast, miR-152 downregulation abrogated the effects induced by siRNA against CTSL treatment., Conclusion: The key findings of this study provided evidence suggesting that miR-152 functions by means of binding to CTSL to induce GIST cell apoptosis and inhibit proliferation, migration, and invasion. The anti-tumor role of miR-152 makes it an attractive therapeutic target for GIST.

Cervical cancer is the fourth most common malignancy among women worldwide, and continued research to discover biomarkers or therapeutic targets will aid early diagnosis and treatment of this cancer. Here, we investigated novel cervical cancer biomarkers using integrated analysis of high-throughput sequencing data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We have identified nine genes of interest that appear to be involved in cervical cancer development: SPARCL1, SYCP2, KIF4A, PRC1, TOP2A, LAMP3, KIF20A, MCM2, and APOBEC3B. Furthermore, gene ontology (GO) and co-expression analysis of these differentially expressed genes indicated that SPARCL1 may play a core role in cervical cancer development. Further, we analyzed the expression of these nine genes during the progression of cervical cancer, and found that SPARCL1 is also related to precancerous lesions and migration processes during cervical cancer pathogenesis. Finally, we validated these observations by investigating SPARCL1 expression in cervical cancer tissue and serum samples. The diagnostic specificity of serum SPARCL1 in cervical cancer occurrence was also compared with other high incidence diseases. All of these data indicate that SPARCL1 may be a novel cancer predictive marker and a potential therapeutic target for tumor development and progression in cervical cancer.

Chameleons are masters of light, expertly changing their color, pattern, and reflectivity in response to their environment. Engineered materials that share this tunability can be transformative, enabling active camouflage, tunable holograms, and novel colorimetric medical sensors. While progress has been made in creating artificial chameleon skin, existing schemes often require external power, are not continuously tunable, and may prove too stiff or bulky for applications. Here, a chemically tunable, large-area metamaterial is demonstrated that accesses a wide range of colors and refractive indices. An ordered monolayer of nanoresonators is fabricated, then its optical response is dynamically tuned by infiltrating its polymer substrate with solvents. The material shows a strong magnetic response with a dependence on resonator spacing that leads to a highly tunable effective permittivity, permeability, and refractive index spanning negative and positive values. The unity-order index tuning exceeds that of traditional electro-optic and photochromic materials and is robust to cycling, providing a path toward programmable optical elements and responsive light routing., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The aim of this study was to investigate the correlation of expression of IGF1R-RACK1-STAT3 and Bcl-xl in nasopharyngeal carcinoma (NPC) with the clinicopathological features and the prognosis of NPC. Our study selected 215 NPC tissues and 178 chronic nasopharyngitis tissues (control group). Positive expression rates of IGF1R, RACK1, STAT3, and Bcl-xl were tested by immunohistochemical method, and expression of IGF1R, RACK1, STAT3, Bcl-xl, Bcl-2, and Bax by western blotting. Correlation of IGF1R, RACK1, STAT3, and Bcl-xl with the clinicopathological features of NPC was analyzed. The correlation among those four expression was analyzed by Spearman. The survival of NPC and independent factors of prognosis were tested by Kaplan-Meier and COX proportional hazards model respectively. The NPC group had higher positive expression rates of IGF1R, RACK1, STAT3, and Bcl-xl, and elevated expression of IGF1R, RACK1, STAT3, Bcl-xl, Bcl-2, and Bax. The lymph node metastasis (LNM) group had higher positive expression rates of IGF1R and RACK1 when compared with the non-LNM group. Patients with stage III and IV had higher positive expression rates of IGF1R, RACK1, STAT3, and Bcl-xl. There was positive correlation between expression of IGF1R and RACK1, STAT3. Such correlation was found between RACK1 and STAT3. Patients with negative expression of IGF1R, RACK1, STAT3, and Bcl-xl had higher survival rates. The risky factors of poor prognosis of NPC were positive expression of IGF1R, RACK1, STAT3 and Bcl-xl, and LNM. IGF1R-RACK1-STAT3 and Bcl-xl expression correlated with the clinicopathological features and poor prognosis of NPC., (© 2017 Wiley Periodicals, Inc.)

We aim to investigate the interaction between the EZH2 and the long noncoding RNA (lncRNA) SPRY4-IT1. We also explore their respective effects on human lung adenocarcinoma (LA) cell invasion and migration. Both LA and adjacent normal tissues were obtained from 256 LA patients. SPTY4-IT expression and EZH2 mRNA expressions in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The siRNAs against SPRY4-IT1 and EZH2 were co-transfected into A549 and H1975 cells. The interaction between SPRY4-IT1 and EZH2 was determined using a RNA pull-down assay and a RNA immunoprecipitation (RIP) assay. A Transwell assay and scratch assay were used to evaluate the cell migration and invasion abilities. The expressions of E-cadherin and Vimentin in the epithelial-mesenchymal transition (EMT) and EZH2 protein expression were detected through western blotting. SPRY4-IT1 expression was observed to be significantly lower, while the expression of EZH2 was higher in the LA tissues than in the adjacent normal tissues. Compared with the HBE cell line, expressions of SPRY4-IT1 in each human LA cell line had decreased, with the lowest observed reduction in the A549 cell line, while EZH2 mRNA and protein expression increased in each human LA cell lines. After SPRY4-IT1-siRNA was transfected into A549 and H1975 cells, invasion and migration abilities were enhanced, in addition to a reduction in the expression of E-cadherin, while expressions of Vimentin exhibited an increased rate. Consequently, we find that EZH2 promotes LA cell invasion and metastasis by inhibiting SPRY4-IT1 expression., (© 2017 Wiley Periodicals, Inc.)

Our study was performed to elucidate how SOCS-1/3 silencing suppresses renal interstitial fibrosis (RIF) by alleviating renal tubular damage in rat models affected by hydronephrosis. Male Wistar rats were randomly selected to establish hydronephrosis rat model, after which all rats were classified into normal, model, negative control (NC), siRNA-SOCS-1, siRNA-SOCS-3, and siRNA-SOCS-1 + siRNA-SOCS-3 groups. The levels of urine protein, serum creatinine (Scr), and blood urea nitrogen (BUN) were detected. ELISA was performed to determine levels of cystatin (CysC), β2-microglobulin (β2-MG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. RT-qPCR and Western blotting were used for mRNA and protein expressions of SOCS-1, SOCS-3, α-smooth muscle actin (α-SMA), and transforming Growth Factor (TGF)-β1. Compared with the normal group, the levels of Scr, BUN, urine protein, NAG, CysC, β2-MG, IL-6, and TNF-α were increased in other groups, as well as elevated mRNA and protein expressions of SOCS-1, SOCS-3, α-SMA, and TGF-β1. The siRNA-SOCS-1, siRNA-SOCS-3, and siRNA-SOCS-1 + siRNA-SOCS-3 groups were found with decreased levels of Scr, BUN, urine protein, NAG, CysC, β2-MG, IL-6, and TNF-α, as well as mRNA and protein expressions of SOCS-1, SOCS-3, α-SMA, and TGF-β1, including positive rates of SOCS-1 and SOCS-3 proteins in comparison with the model and NC groups. In comparison with the siRNA-SOCS-1 and siRNA-SOCS-3 groups, the siRNA-SOCS-1 + siRNA-SOCS-3 group exhibited decreased levels of Scr, BUN, urine protein, NAG, CysC, β2-MG, IL-6, and TNF-α. Our study demonstrated that silencing of SOCS-1/3 may suppress RIF by alleviating the renal tubular damage in rat models affected by hydronephrosis., (© 2017 Wiley Periodicals, Inc.)

Background/aims: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism., Methods: SDS and LiCl (activators of the Wnt/β-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/β-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 µmol/L SDS or LiCl alone or with both in combination for 1 h followed by a 24-h incubation with 100 µmol/L 6-OHDA to obtain in vitro data., Results: In vivo the administration of LiCl was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3β phosphorylation (GSK-3β-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3β mRNA level; as well as elevate β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCl on 6-OHDA-injected rats. In vitro LiCl treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCl treatment increased SOA activity, GSH-Px levels, and GSK-3β-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GSK-3β mRNA levels; as well as increased β-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCl on 6-OHDA-treated PC12 cells., Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/β-catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: MiRNAs are involved in phenotype modulation of neural cells after peripheral nerve injury. However, the roles of miRNAs on the survival of dorsal root ganglion (DRG) neurons have not yet been fully understood., Methods: In this study, the expression of miR-142-3p was measured in rat DRGs (L4-L6) during the initial 24 hours post sciatic nerve transection by microarray profiling and quantitative PCR. The functional assays including the cell viability, colony formation, cell cycle and apoptosis assays were performed in miR-142-3p mimic or inhibitor transfected cell lines., Results: MiR-142-3p was identified to be siginificantly upregulated in rat DRGs (L4-L6) during the initial 24 hours post sciatic nerve transection. MiR-142-3p mimic enhanced cell viability by promoting cell cycle and inhibiting cell apoptosis in cultured DRG neurons. In addition, cyclin-dependent kinase inhibitor 1B (CDKN1B, also known as p27/Kip1) and tissue inhibitor of metalloproteinase 3 (TIMP3) were identified as targets of miR-142-3p. Furthermore, knockdown of CDKN1B or TIMP3 by specific siRNAs could reverse the effect of miR-142-3p., Conclusions: In the conclusion, the results showed that miR-142-3p could promote neuronal cell cycle and inhibit apoptosis at least partially through suppressing CDKN1B and TIMP3 after peripheral nerve injury., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Inflammation plays a crucial role in the pathogenesis of stroke. This study aims to determine lipoprotein (a) [Lp(a)] levels in serum and to investigate their associations with stroke recurrence events in a 3-month follow-up study in patients with acute ischemic stroke (AIS). Serum Lp(a) levels were determined in 203 ischemic stroke patients and 120 normal controls at admission. The severity and clinical outcome of ischemic stroke patients were evaluated by the National Institutes of Health Stroke Scale (NIHSS). We followed the participants for a median of 3 months using a standard questionnaire to determine the stroke recurrence events. The correlation analysis and multiple linear regression analysis were performed. Compared with controls, serum Lp(a) levels were significantly increased in ischemic stroke patients than in controls. NIHSS scores and infarct volume were positively correlated with Lp(a) (P < 0.001). Finally, 34 patients (16.7%; 95% CI, 11.6-21.9%) had a stroke recurrence. Serum Lp(a) levels in patients with recurrent stroke were significantly higher as compared with those in patients without recurrent stroke (P < 0.001). In multivariate analysis, there was an increased risk of stroke recurrence associated with Lp(a) levels ≥300 mg/l (OR, 2.87; 95% CI, 1.98-4.32; P = 0.009) after adjusting for possible confounders. With an AUC of 0.872 (95% CI, 0.816-0.927), Lp(a) showed a significantly greater discriminatory ability to predict stroke recurrence as compared with NIHSS score (AUC, 0.782; 95% CI, 0.704-0.859; P < 0.01). Our findings suggest that elevated serum Lp(a) levels can predict the risk of early stroke recurrence in patients with first-ever ischemic stroke. Further research is needed to replicate these findings.

Objective: The aim of this study was to evaluate the mechanisms involved with miRNA-708 and its targeting of bone morphogenetic protein and activin membrane-bound inhibitor in cell proliferation, migration, and apoptosis in mice with melanoma via the Wnt and transforming growth factor β signaling pathways., Methods: Sixty mice were recruited of which 40 were subsequently assigned into the experimental group (22 mice were successfully established as melanoma model and 18 mice used in tumor xenograft), and the normal control group consisted of 20 mice. B16 cells were assigned to the normal, blank, and negative control, miR-708 mimics, miR-708 inhibitors, si-BAMBI, and miR-708 inhibitors + si-bone morphogenetic protein and activin membrane-bound inhibitor groups. Western blotting and reverse transcription quantitative polymerase chain reaction were employed to detect the expression levels within the tissues and cell lines. TCF luciferase reporter (TOP-FLASH) or a control vector (FOP-FLASH) was applied to detect the activity of the Wnt signaling pathway. MTT3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay, flow cytometry, scratch test, and Transwell assay were conducted, respectively, for cell proliferation, apoptosis, migration, and invasion, while tumor xenograft procedures were performed on the nude mice recruited for the study., Results: Compared to the normal control group, the model group displayed increased expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2; TOPflash activity; β-catenin expression; cell proliferation; migration; and invasion capabilities while decreased expressions of miR-708, vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3 and apoptosis rate. Compared to the blank and negative control groups, the miR-708 mimics and small-interfering RNA-bone morphogenetic protein and activin membrane-bound inhibitor groups exhibited decreases expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2 and decreased proliferation, migration, and invasion capabilities, while increases in the apoptosis rate, expressions of vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3; however, downregulated levels of TOPflash activity and β-catenin expression were recorded. The miR-708 inhibitors group displayed an opposite trend., Conclusion: Downregulation of miR-708-targeted bone morphogenetic protein and activin membrane-bound inhibitor inhibits the proliferation and migration of melanoma cells through the activation of the transforming growth factor β pathway and the suppression of Wnt pathway.

Background/aims: Spinal cord glioma is a highly aggressive malignancy that commonly results in high mortality due to metastasis, high recurrence and limited treatment regimens. This study aims to elucidate the effects of long non-coding RNA LINC01260 (LINC01260) on the proliferation, migration and invasion of spinal cord glioma cells by targeting Caspase recruitment domain family, member 11 (CARD11) via nuclear factor kappa B (NF-κB) signaling., Methods: The Multi Experiment Matrix (MEM) website was used for target gene prediction, and the DAVID database was used for analysis of the relationship between CARD11 and the NF-κB pathway. In total, 60 cases of glioma tissues and adjacent normal tissues were collected. Human U251 glioma cells were grouped into blank, negative control (NC), LINC01260 vector, CARD11 vector, siRNA-LINC01260, siRNA-CARD11, LINC01260 vector + CARD11 vector and LINC01260 + siRNA-CARD11 groups. A dual-luciferase reporter assay was conducted to verify the target relationship between LINC01260 and CARD11. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were employed to assess expression of LINC01260, E-cadherin, p53, CARD11, Ki67, N-cadherin, matrix metalloproteinase (MMP)-9, NF-κBp65 and NF-κBp50. MTT, flow cytometry, wound-healing and Transwell assays were performed to examine cell viability, the cell cycle, apoptosis, invasion and migration. Tumor growth was assessed through xenografts in nude mice., Results: CARD11 was confirmed to be a target gene of LINC01260 and was found to be involved in regulating the NF-κB pathway. Compared with adjacent normal tissues, glioma tissues showed reduced expression of LINC01260 and elevated expression of CARD11 and genes related to apoptosis, invasion and migration; activation of NF-κB signaling was also observed. In contrast to the blank and NC groups, an elevated number of cells arrested in G1 phase, increased apoptosis and reduced cell proliferation, invasion and number of cells arrested in S and G2 phases, as well as tumor growth were found for the LINC01260 vector and siRNA-CARD11 groups., Conclusions: Our findings demonstrate that overexpression of LINC01260 inhibits spinal cord glioma cell proliferation, migration and invasion by targeting CARD11 via NF-κB signaling suppression., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Parkinson's disease (PD) is a neurodegenerative movement disease with a high annual incidence. Accumulating evidence demonstrates that microRNAs play important roles in the pathogenesis of multiple neurological disorders, including PD. This study aims to investigate how microRNA-200a (miR-200a) regulates striatal dopamine receptor D2 (DRD2) to affect apoptosis of striatum in rats with PD and to explore the associated mechanism., Methods: After successfully establishing a PD model by 6-hydroxydopamine injections, PD rats were mainly treated with miR-200a mimics, inhibitors, Forskolin or a combination of miR-200a inhibitors and Forskolin. High-performance liquid chromatography-electrochemical detection (HPLC-ECD) was employed to detect the levels of dopamine, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and chemistry colorimetric methods were applied to detect the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). A TUNEL assay and immunocytochemical staining were performed to observe apoptosis and tyrosine hydroxylase (TH)-positive cells in the striatum. The expression of miR-200a, DRD2, Bad, Bax, Bcl-2, cAMP and PKA was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays., Results: In the cellular experiments, after transfection with the inhibitor of miR-200a, decreased levels of Bax, GSH-Px, SOD, dopamine, DOPAC and HVA but increased levels of MDA and Bcl-2 were found along with a reduced apoptosis rate and increased TH-positive cell number. In addition, downregulating miR-200a resulted in lower expression of AKT, cAMP and PKA but higher expression of DRD2 and CREB, indicating that the downregulation of miR-200a increases DRD2 expression, which blocks the cAMP/PKA signaling pathway., Conclusion: This study provides evidence that the inhibition of miR-200a can repress apoptosis in the striatum via inhibition of the cAMP/PKA signaling pathway by upregulating DRD2 expression in PD rats., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background/aims: Recent studies have reported the importance of tubulin alpha 4b (TUBA4B), a long non-coding RNA, in the development of several cancers; however, studies on its clinical significance are rare. In the present meta-analysis, we investigated whether TUBA4B can be used as a prognostic biomarker in human cancers., Methods: A comprehensive search was performed in PubMed, Embase, Web of Science, and the Gene Expression Omnibus databases. Hazard ratios from individual studies were calculated and pooled using a random-effects or fix-effects model. The pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the value of TUBA4B. The expression of TUBA4B was evaluated in lung cancer tissue arrays by fluorescence in situ hybridization assay. Additionally, a sensitivity analysis and Begg's test were conducted., Results: We found that TUBA4B was significantly correlated with overall survival (OS) (HR = 1.33, 95% CI: 1.16-1.52, P=0.000), disease-free survival (DFS; HR = 1.25, 95% CI: 1.06-1.48, P=0.007), and recurrence-free survival (RFS; HR = 1.42, 95% CI: 1.26-1.60, P=0.000). In addition, TUBA4B was a risk factor for lung cancer (HR = 1.24, 95% CI: 1.03-1.49, P=0.021), colon cancer (HR = 1.67, 95% CI: 1.02-2.74, P=0.042), breast cancer (HR = 1.52, 95% CI: 1.10-2.12, P=0.012), and ovarian cancer (HR = 1.67, 95% CI: 1.18-2.36, P=0.004). Moreover, LncRNA-TUBA4B was significantly lower expression in tumor tissues than normal lung tissues (P< 0.001). The expression of lncRNA-TUBA4B was decreased with the progression of lung cancer stage. A subgroup meta-analysis based on data resource, sample size, region, patient numbers, and tumor type was further performed. Our studies revealed that tumor tissues with low levels of TUBA4B was significantly associated with short OS, DFS, and RFS in cancer patients., Conclusion: The present findings suggest that TUBA4B can be a novel biomarker for the prognosis of various cancers., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background: Allergic asthma is a complex genetic disorder that involves interactions between genetic and environmental factors. Usage of PTEN may be a good therapeutic strategy for the management of allergic inflammation. Thus, the present study aims to explore the effects of phosphatase and tensin homolog ( PTEN ) gene silencing on airway remodeling and proliferation of airway smooth muscle cells (ASMCs) in a mouse model of allergic asthma., Methods: A total of 56 healthy female BABL/c mice (weighing between 16 to 22 grams) were selected and were assigned on random into ovalbumin (OVA; mice were stimulated with OVA to induce allergic asthma), OVA + si-PTEN, normal saline (NS; mice were treated with normal saline) and NS + si-PTEN groups. Masson staining was employed in order to observe lung tissue sections. Immunohistochemical staining was used to detect the expression of α-SMA + . Gene silencing was conducted in the NS + si-PTEN and OVA + si-PTEN groups. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were used to detect the mRNA and protein expressions of PTEN in ASMCs of each group. CCK-8 assay and flow cytometry were performed to determine the cell proliferation rate and cell cycle., Results: Airway remodeling and changes of smooth muscle layer were found in allergic asthmatic mice with thick airway walls. The expression of alpha smooth muscle actin (α-SMA + ) was significantly higher in ASMCs of the OVA, OVA + si-PTEN and NS + si-PTEN groups compared with ASMCs of the NS group. The mRNA and protein expressions of PTEN reduced in the OVA, OVA + si-PTEN and NS + si-PTEN groups. The rate of ASMCs proliferation in OVA, OVA + si-PTEN and NS + si-PTEN groups were significantly higher than the NS group. The proportion of ASMCs in S and G2 stages increased, while the number of cells in the G1 stage decreased after PTEN gene silencing., Conclusions: These results demonstrated that PTEN gene silencing might promote proliferation of ASMCs and airway remodeling in a mouse model of allergic asthma., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.