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1.
PLoS One ; 15(2): e0228874, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049977

RESUMO

Matriptase plays important roles in epithelial integrity and function, which depend on its sorting to the basolateral surface of cells, where matriptase zymogen is converted to an active enzyme in order to act on its substrates. After activation, matriptase undergoes HAI-1-mediated inhibition, internalization, transcytosis, and secretion from the apical surface into the lumen. Matriptase is a mosaic protein with several distinct protein domains and motifs, which are a reflection of matriptase's complex cellular itinerary, life cycle, and the tight control of its enzymatic activity. While the molecular determinants for various matriptase regulatory events have been identified, the motif(s) required for translocation of human matriptase to the basolateral plasma membrane is unknown. The motif previously identified in rat matriptase is not conserved between the rodent and the primate. We, here, revisit the question for human matriptase through the use of a fusion protein containing a green fluorescent protein linked to the matriptase N-terminal fragment ending at Gly-149. A conserved seven amino acid motif EEGEVFL, which is similar to the monoleucine C-terminal to an acidic cluster motif involved in the basolateral targeting for some growth factors, has been shown to be required for matriptase translocation to the basolateral plasma membrane of polarized MDCK cells. Furthermore, time-lapse video microscopy showed that the motif appears to be required for entry into the correct transport vesicles, by which matriptase can undergo rapid trafficking and translocate to the plasma membrane. Our study reveals that the EEGEVFL motif is necessary, but may not be sufficient, for matriptase basolateral membrane targeting and serves as the basis for further research on its pathophysiological roles.

2.
Gene ; : 144411, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006596

RESUMO

Long non-coding RNAs (lncRNAs) have been identified in cerebral ischemia-reperfusion (I/R) injury nowadays. Herein, we uncovered the function and underlying mechanism of the lncRNA Rian in cerebral I/R injury. The oxygen-glucose deprivation model in N2a cells was offered to mimic cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 activity were used to evaluate cell apoptosis. Then, middle cerebral artery occlusion was conducted to evaluate the function of lncRNA Rian in mice. Real-time PCR and western blotting were performed to determine the expression of lncRNA Rian, miR-144-3p, GATA binding protein 3 (GATA3), caspase-3, Bax, and Bcl-2. The results showed that both Rian and GATA3 were downregulated, and miR-144-3p was upregulated in cerebral I/R injury in vitro and in vivo. Overexpression of Rian could inhibit the cell apoptosis induced by oxygen-glucose deprivation. Furthermore, overexpression of Rian distinctly reduced the infarct size, and it also improved the neurological score. Overexpression of Rian could abolish miR-144-3p-mediated I/R injury in vitro and in vivo. Besides, GATA3 was the target of miR-144-3p and GATA3 could be regulated co-operatively by miR-144-3p and Rian. Consequently, these findings showed that the Rian/miR-144-3p/GATA3 axis is an essential signaling in cerebral I/R injury. The lncRNA Rian may serve as a potential target for novel treatment in patients with ischemic stroke.

3.
Mol Cell Endocrinol ; : 110742, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006608

RESUMO

Epidemiological evidence suggests that the etiology and pathogenesis of rheumatoid arthritis (RA) are closely associated with estrogen metabolism and deficiency. Estrogen protects against articular damage. Estradiol replacement therapy ameliorates local inflammation and knee joint swelling in ovariectomized models of RA. The mechanistic basis for the protective role of 17ß-estradiol (17ß-E2) is poorly understood. Acid-sensing ion channel 1a (ASIC1a), a sodium-permeable channel, plays a pivotal role in acid-induced articular chondrocyte injury. The aims of this study were to evaluate the role of 17ß-E2 in acid-induced chondrocyte injury and to determine the effect of 17ß-E2 on the level and activity of ASIC1a protein. Results showed that pretreatment with 17ß-E2 attenuated acid-induced damage, suppressed apoptosis, and restored mitochondrial function. Further, 17ß-E2 was shown to reduce protein levels of ASIC1a through the autophagy-lysosomal pathway, to protect chondrocytes from acid-induced apoptosis, and to induce ASIC1a protein degradation through the ERα receptor. Taken together, these results show that the use of 17ß-E2 may be a novel strategy for the treatment of RA by reducing cartilage destruction through down-regulation of ASIC1a protein levels.

4.
World Neurosurg ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006731

RESUMO

OBJECTIVE: To perform a comprehensive meta-analysis to systematically assess the value of abnormal muscle response (AMR) in predicting the surgical outcome of patients with hemifacial spasm (HFS). METHODS: The electronic database PubMed, Embase, Web of Science and ScienceDirect were searched, and relevant articles were identified up to September 30, 2019. The data were extracted for pooled analysis, heterogeneity testing, sensitivity analysis, publication bias analysis, and Fagan plot analysis. RESULTS: The disappearance of AMR during microvascular decompression (MVD) was associated with a favorable short-term surgical outcome (pooled RR [relative risk], 1.42; 95% confidence interval [CI], 1.24-1.62; pooled RR adjusted for publication bias, 1.30; 95% CI, 1.08-1.57). The corresponding pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic Odds Ratio (DOR) were 0.91 (95% CI, 0.88-0.94), 0.34 (95% CI, 0.27-0.42), 1.4 (95% CI, 1.2-1.6), 0.26 (95% CI, 0.17-0.38) and 5 (95% CI, 3-9), respectively. The disappearance of AMR was almost ineffective in predicting the long-term surgical outcome (pooled RR, 1.09; 95% CI, 1.02-1.17; pooled RR adjusted for publication bias, 1.001; 95% CI, 0.92-1.09). The corresponding pooled sensitivity, specificity, PLR, NLR, and DOR were 0.90 (95% CI, 0.85-0.93), 0.28 (95% CI, 0.20-0.37), 1.2 (95% CI, 1.1-1.4), 0.38 (95% CI, 0.22-0.63) and 3 (95% CI, 2-6), respectively. CONCLUSIONS: The disappearance of AMR during MVD demonstrate limited prognostic value for a favorable short-term outcome, and does not appear effective in predicting the long-term outcome of patients with HFS.

5.
Sci Total Environ ; 714: 136811, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32018970

RESUMO

To test the relationship not yet explored before among earthquake and related environmental factors, low-density lipoprotein receptor (LDLR) and posttraumatic stress disorder (PTSD), the genetic variation of LDLR rs5925 was selected and PTSD was examined by PTSD Checklist-Civilian Version (PCLC) in adolescents with different genotypes of LDLR rs5925 longitudinally at 6, 12 and 18 months after the 2008 Wenchuan earthquake. The C allele carriers were observed to have higher PTSD prevalence than the TT homozygotes in the male subjects, and higher PTSD prevalence and PCL-C scores in the female subjects only at 6 months. When compared to that at 12 months, decreased PTSD prevalence was observed at 18 months only in the female C allele carriers, but not in the female TT homozygotes or the male subjects. The potential risk factors of PTSD and predictors of PCL-C scores were different during the follow-up. LDLR rs5925 was one of the predictors for PCL-C scores at 6 and 12 months, and one of the potential factors for PTSD prevalence at 6 months. These results suggest that interactions may occur between earthquakes and other related environmental factors, which could affect the relationship of LDLR rs5925 with PTSD and be considered for individualized treatment.

6.
Hum Cell ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034722

RESUMO

95% of the body's testosterone is produced by the Leydig Cells (LCs) in adult testis, and LC functional degradation can cause testosterone deficiency ultimately leading towards hypogonadism. The transplantation of LCs derived from stem cells is a very promising therapy to overcome the testosterone deficiency. The isolated umbilical cord mesenchymal stem cells (UMSCs) were identified by flow cytometry and adipogenic and osteogenic differentiation. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used for the differentiated Leydig-like cell identification. The comparisons of the testosterone levels, gene expression levels, and cyclic adenosine monophosphate (cAMP) productions were performed through radioimmunoassay, quantitative polymerase chain reaction (qPCR), and cAMP assay kit, respectively. Here, it is stated that our isolated human UMSCs, which could positively express CD29, CD44, CD59, CD90, CD105, and CD166 but negatively express CD34 as well as could be differentiated into adipocytes and osteocytes, could be differentiated into Leydig-like cells (UMSC-LCs) using a novel differentiation method based on molecular compounds. The enrichment UMSC-LCs could secrete testosterone into the medium supernatant and produce considerable cAMP at the stimulation of luteinizing hormone (LH), and positively expressed LC lineage-typical markers LHCGR, SCARB1, SATR, CYP11A1, CYP17A1, HSD3B1, HSD17B3, and SF-1 as well as negatively expressed mesenchymal stem cell typical markers CD29, CD44, and CD105. The expression levels of NR3C4, PDGFRA, and NR3A1 in UMSC-LCs were higher than those of UMSCs and were comparable with LCs. These results illuminated that UMSCs could be differentiated into Leydig-like cells using the defined molecular compounds, which might further support MSC-derived Leydig cell transplantation therapy for testosterone insufficiency.

7.
Diabetes Metab ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035968

RESUMO

AIM: We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of non-alcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. MATERIALS AND METHODS: We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a 'strict-normal' TSH group (TSH level 0.4 to 2.5 mIU/l; n=283) and a 'high-normal' TSH group (TSH level 2.5 to 5.3 mIU/l with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of non-alcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. RESULTS: Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio 3.279; 95%CI 1.298-8.284; P = 0.012). CONCLUSION: In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.

8.
Opt Lett ; 45(4): 848-851, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32058486

RESUMO

In this Letter, based on two advanced tunable ultra-flat optical frequency comb generators (T-FOCGs), a coherent channelized receiver with high channelized efficiency and reconfigurability is proposed. In the T-FOCG, the number of 1 dB comb lines increases with the gain, but the optical power of these 1 dB comb lines has almost the constant variance. In the proposed scheme, one optical carrier can support four sub-channels. Meanwhile, the number and bandwidth of sub-channels, as well as the bandwidth and center frequency of an original broadband signal, are all tunable. In this Letter, we verify the feasibility of the coherent channelized receiver by channelizing a 4 GHz signal with a 20 GHz center frequency into four 1 GHz sub-channels, and the reconfigurability is demonstrated by channelizing a 10 GHz signal with frequencies from 18 to 28 GHz into five 2 GHz sub-channels. Moreover, the error-vector magnitude curves of the directly received and the channelized quadrature amplitude modulation (QAM) signal at different amounts of beat noise are compared.

9.
Artif Life ; : 1-15, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027528

RESUMO

Susceptibility to common human diseases such as cancer is influenced by many genetic and environmental factors that work together in a complex manner. The state of the art is to perform a genome-wide association study (GWAS) that measures millions of single-nucleotide polymorphisms (SNPs) throughout the genome followed by a one-SNP-at-a-time statistical analysis to detect univariate associations. This approach has identified thousands of genetic risk factors for hundreds of diseases. However, the genetic risk factors detected have very small effect sizes and collectively explain very little of the overall heritability of the disease. Nonetheless, it is assumed that the genetic component of risk is due to many independent risk factors that contribute additively. The fact that many genetic risk factors with small effects can be detected is taken as evidence to support this notion. It is our working hypothesis that the genetic architecture of common diseases is partly driven by non-additive interactions. To test this hypothesis, we developed a heuristic simulation-based method for conducting experiments about the complexity of genetic architecture. We show that a genetic architecture driven by complex interactions is highly consistent with the magnitude and distribution of univariate effects seen in real data. We compare our results with measures of univariate and interaction effects from two large-scale GWAS studies of sporadic breast cancer and find evidence to support our hypothesis that is consistent with the results of our computational experiment.

12.
BMC Pediatr ; 20(1): 64, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046672

RESUMO

BACKGROUND: To evaluate the safety of using fluoroquinolones in pediatric population in Taiwan. METHODS: Patients aged 0~18 years old with fluoroquinolones prescriptions ≥5 consecutive days during year 2000 to 2013 were selected from the National Health Insurance Research Database, 4-time case number were selected as controls. We evaluated the patient's outcome after the use of fluoroquinolones by reviewing a newly diagnosis of the following collagen-associated adverse events by International Classification of Diseases, Ninth Revision, Clinical Modification codes, covering tendons rupture, retinal detachments, gastrointestinal tract perforation, aortic aneurysm or dissection. RESULTS: Of the enrolled patients (n = 167,105), collagen-associated adverse effects developed in 85 cases (0.051%) in 6-month tracking, including 0.051% in the fluoroquinolones study cohort (17 in 33,421) and 0.051% (68 in 133,684) in the fluoroquinolones free comparison cohort. The crude hazard ratio for collagen-associated adverse events in the fluoroquinolones group was 0.997 (0.586-1.696; p = 0.990). After adjusting for age, sex, catastrophic illness, low-income household, seasons, levels of urbanization, and healthcare, the corrected hazard ratio in 6-month tracking with FQs was 1.330 (95% CI; 0.778-2.276; p = 0.255). CONCLUSIONS: There is no significant difference of collagen-associated adverse effects between fluoroquinolones group and fluoroquinolones free group from our data. We propose that fluoroquinolones for pediatric population in clinical practice may be not so harmful as previous references reported.

13.
Environ Int ; 137: 105519, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014790

RESUMO

Soils in coastal areas of the land-sea interface are vulnerable to heavy metal (HM) accumulation and subsequently to human health risk. However, few studies have investigated the HM pollution and risk in soils along the coastal areas of the Yellow Sea Large Marine Ecosystem (YSLME), in an international perspective. This study is the first comprehensive work in the YSLME encompassing 122 coastal locations along the Bohai Sea (BS), Yellow Sea of China (YSC), and Yellow Sea of South Korea (YSK). Soil HM pollution showed great spatial variations cross the regions and countries. Accumulations of As, Cu, Pb, and Zn in the YSK were significantly higher than those in the BS and YSC (p < 0.05). Whilst the elevated Cd, Hg, and Ni in soils were found in the BS and YSC compared to those in the YSK (p < 0.05). Meantime, the assessment of ecological risk posed by HMs indicated higher potential risk in the BS than other coastal areas. In specific, Cd and Hg posed a higher risk in the BS and YSC, while As showed relatively high risk in the YSK, indicating site-dependent accumulation of HMs in soils. Soil pH and organic matter were found to be important factors affecting the HM accumulation in the study areas. Industrial activities are the major driving factors influencing spatial distributions of HMs, and such activities exhibited different degrees of influence across the sampling sites. Altogether, the results of present study first identified the bilateral characteristics of soil HM pollution along the entire coasts of the YSLME in a comprehensive manner in several aspects: (1) sources, (2) hot spots, (3) priority chemicals of concern, and (4) site-specific potential risk of the soil HMs. Overall, this study provides references and backgrounds for future environmental management strategies and aids in developing a bilateral government policy towards coastal pollution management of HMs from an international scale and perspective.

14.
Neurochem Int ; 135: 104692, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032636

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) has therapeutic effects on Parkinson's disease (PD). Warburg effect, namely aerobic glycolysis, is benefit to PD. Leptin, a hormone secreted in adipose, plays an important role in the treatment of PD. OBJECTIVE: To determine whether the mechanism underlying protection of H2S against PD is involved in promoting Warburg effect via upregulation of leptin. METHODS: We set a PD model via unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in Sprague Dawley rat. PD-like behavior was analyzed by apomorphine-induced rotations, open field activity test, stepping test and cylinder test. Dopaminergic neurons were detected by immunohistochemistry. The expressions of Hexokinase-2, pyruvate kinase M-2, lactate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase, and leptin were measured by Western blot. Lactate dehydrogenase (LDHA) activity was monitored by ELISA. The lactate content was measured by lactate assay kit. RESULTS: We showed that NaHS (a donor of H2S) prevented 6-OHDA-induced PD-like behaviors as well as the loss of dopaminergic neurons. We also found that NaHS enhanced the Warburg effect and upregulated leptin expression in the substantia nigra of 6-OHDA-exposed rats. While, inhibited leptin signaling by OBR13-A reversed the protections of H2S against 6-OHDA-exerted PD-like behaviors and the loss of dopaminergic neurons in the substantia nigra, and abolished H2S-enhanced in the Warburg effect in the substantia nigra. CONCLUSION: These data indicated that leptin mediates the protection of H2S against PD, which involves enhancing the Warburg effect of the substantia nigra.

15.
Pharmacol Ther ; : 107503, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061923

RESUMO

Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4is) are oral anti-diabetic drugs (OADs) for the treatment of type 2 diabetes mellitus (T2DM) through inhibiting the degradation of incretin peptides. Numerous investigations have been focused on the effects of DPP4is on glucose homeostasis. However, there are limited evidences demonstrating their Potential modulatory functions in the immune system. DPP4, originally known as the lymphocyte cell surface protein CD26, is widely expressed in many types of immune cells including CD4(+) and CD8(+) T cells, B cells, NK cells, dendritic cells, and macrophages; and regulate the functions of these cells. In addition, DPP4 is capable of modulating plenty of cytokines, chemokines and peptide hormones. Accordingly, DPP4/CD26 is speculated to be involved in various immune/inflammatory diseases and DPP4is may become a new drug class applied in these diseases. This review focuses on the regulatory effects of DPP4is on immune functions and their possible underlying mechanisms. Further clinical studies will be necessitated to fully evaluate the administration of DPP4is in diabetic patients with or without immune diseases.

16.
BMC Public Health ; 20(1): 159, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013898

RESUMO

BACKGROUND: Our aim was to explore the concepts of health and well-being from the point of view of the people experiencing them. Most of the efforts to understand these concepts have focused on disease prevention and treatment. Less is known about how individuals achieve health and well-being, and their roles in the pursuit of a good life. We hoped to identify important components of these concepts that may provide new targets and messages to strengthen existing public health programs. An improved understanding of health and well-being - or what it means to be well - can guide interventions that help people lead healthier, more fulfilling lives. METHODS: Using a grounded qualitative approach drawing from narrative inquiry, we interviewed 24 Taiwanese adults. Thematic inductive coding was employed to explore the nature of health and well-being. RESULTS: Eight constituent domains emerged regarding well-being and health. While the same domains were found for both constructs, important frequency differences were found when participants discussed health versus well-being. Physical health and lifestyle behaviors emerged as key domains for health. Disease-related comments were the most frequently mentioned sub-category within the physical health domain, along with health care use and aging-related changes. For well-being, family and finances emerged as key domains. Family appears to be a cornerstone element of well-being in this sample, with participants often describing their personal well-being as closely tied to - and often indistinguishable from - their family. Other domains included work-life, sense of self, resilience, and religion/spirituality. CONCLUSIONS: Health and well-being are complex and multifaceted constructs, with participants discussing their constituent domains in a very interconnected manner. Programs and policies intended to promote health and well-being may benefit from considering these domains as culturally-appropriate leverage points to bring about change. Additionally, while the domains identified in this study are person-centered (i.e., reflecting the personal experiences of participants), the stories that participants offered provided insights into how well-being and health are influenced by structural, societal and cultural factors. Our findings also offer an opportunity for future refinement and rethinking of existing measurement tools surrounding these constructs.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32033265

RESUMO

Desertification has inflicted severe damage on the natural environment and social economy for decades, particularly in the arid and semi-arid regions of northern China. In Yanchi County, a series of projects were implemented to combat desertification after 2000. To assess the effects of these Desertification Control Projects from the farmers' perspective, we divided Yanchi County into two regions (the northern and southern regions) according to their different environmental conditions. We collected data including basic family information, farmers' perceptions and attitudes, and farmers' suggestions, in a questionnaire investigation following the Participatory Rural Appraisal approach. Data analysis using the Mann-Whitney U test and Fisher's exact test revealed that the Desertification Control Projects were generally successful, as the local environment and farmers' incomes were both improved. Farmers were all satisfied with the effects of the projects, but the farmers in the southern region had a higher acceptance of the projects than those in the northern region. In addition, three problems with the Desertification Control Projects were noted: the farmers had a low degree of participation in the projects, the farmer's low incomes affected the sustainability of the projects, and the implementation of the complete grazing ban had several adverse effects. We provided suggestions for solving these problems. Our findings have important implications for assessing the effects of environmental conservation projects, especially from a participant's perspective.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32064665

RESUMO

Epoxides are widely used chemicals, the determination of which is of paramount importance. Herein, we present an enzyme-based approach for non-instrumental detection of epoxides in standard solution and environmental samples. Halohydrin dehalogenase (HheC) as a biological recognition element and epichlorohydrin as a model analyte were evaluated for sensing. The detection is based on the color change of the pH indicator dye bromothymol blue caused by the HheC-catalyzed ring-opening of the epoxide substrate. The color change is then exploited for the determination of epoxide using a smartphone as an image acquisition and data processing device, eliminating the need for computer-based image analysis software. The color parameters were systematically evaluated to determine the optimum quantitative analytical parameter. Under optimal conditions, the proposed enzyme-based detection system showed a linear range of 0.13-2 mM with a detection limit of 0.07 mM and an assay time of 8 minutes. In addition, the repeatability expressed as relative standard deviation was found to be below 5% (n = 6). Validation with gas chromatographic analyses showed that the proposed enzyme-based epoxide detection could be an alternative way in the quantitative determination of epoxides, and particularly useful in resource-limited settings. This article is protected by copyright. All rights reserved.

19.
Am J Epidemiol ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31942603

RESUMO

Funnel plots have been widely used to detect small study effects in the results of univariate meta-analyses. However, there is no existing visualization tool that is the counterpart of the funnel plot in the multivariate setting. We propose a new visualization method, the galaxy plot, which can simultaneously present the effect sizes of bivariate outcomes and their standard errors in a two-dimensional space. We illustrate the use of galaxy plot by two case studies, including a meta-analysis of hypertension trials with studies from 1979 to 1991, and a meta-analysis of structured telephone support or non-invasive telemonitoring with studies from 1966 to 2015. The galaxy plot is an intuitive visualization tool that can aid in interpretation of results of multivariate meta-analysis. It preserves all of the information presented by separate funnel plots for each outcome while elucidating more complex features that may only be revealed by examining the joint distribution of the bivariate outcomes.

20.
Biol Res ; 53(1): 1, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907031

RESUMO

BACKGROUND: Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson's disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. RESULTS: Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. CONCLUSION: SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.

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