Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.160
Filtrar
1.
Curr Biol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035480

RESUMO

Hyperosmotic stress caused by drought and salinity is a significant environmental threat that limits plant growth and agricultural productivity. Osmotic stress induces diverse responses in plants including Ca2+ signaling, accumulation of the stress hormone abscisic acid (ABA), reprogramming of gene expression, and altering of growth. Despite intensive investigation, no global regulators of all of these responses have been identified. Here, we show that the Ca2+-responsive phospholipid-binding BONZAI (BON) proteins are critical for all of these osmotic stress responses. A Ca2+-imaging-based forward genetic screen identified a loss-of-function bon1 mutant with a reduced cytosolic Ca2+ signal in response to hyperosmotic stress. The loss-of-function mutants of the BON1 gene family, bon1bon2bon3, are impaired in the induction of gene expression and ABA accumulation in response to osmotic stress. In addition, the bon mutants are hypersensitive to osmotic stress in growth inhibition. BON genes have been shown to negatively regulate plant immune responses mediated by intracellular immune receptor NLR genes including SNC1. We found that the defects of the bon mutants in osmotic stress responses were suppressed by mutations in the NLR gene SNC1 or the immunity regulator PAD4. Our findings indicate that NLR signaling represses osmotic stress responses and that BON proteins suppress NLR signaling to enable global osmotic stress responses in plants.

2.
Science ; 370(6513): 192-197, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033214

RESUMO

High-rate lithium (Li) ion batteries that can be charged in minutes and store enough energy for a 350-mile driving range are highly desired for all-electric vehicles. A high charging rate usually leads to sacrifices in capacity and cycling stability. We report use of black phosphorus (BP) as the active anode for high-rate, high-capacity Li storage. The formation of covalent bonds with graphitic carbon restrains edge reconstruction in layered BP particles to ensure open edges for fast Li+ entry; the coating of the covalently bonded BP-graphite particles with electrolyte-swollen polyaniline yields a stable solid-electrolyte interphase and inhibits the continuous growth of poorly conducting Li fluorides and carbonates to ensure efficient Li+ transport. The resultant composite anode demonstrates an excellent combination of capacity, rate, and cycling endurance.

3.
Macromol Rapid Commun ; : e2000517, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047402

RESUMO

Pendant selenium-containing maleimide polymers with different selenium contents are synthesized via a radical copolymerization of styrene and N-butylmaleimide phenyl selenide. The polymer structures are characterized by nuclear magnetic resonance, gel permeation chromatography, Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, and scanning electron microscopy with an energy-dispersive spectrometer, which results in the desired structures and selenium contents. The refractive indices of the polymers, which change as a function of different contents of selenium and oxidative stimuli by H2 O2 or O3 , are investigated. Finally, a photonic crystal (PC) is prepared based on the selenium-containing polymer. The visible color changes of the PC are investigated as a function of different concentrations and contact times of O3 .

4.
Cell Cycle ; : 1-15, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064959

RESUMO

Objective: MicroRNAs (miRNAs) are known to participate in the progression of human cancers, such as pancreatic cancer (PC), while the mechanisms of miR-223 in PC remain largely unknown. This study was for the investigation of the status of microRNA (miR)-223 in the growth of PC with the involvement of ZIC1 and the PI3K/Akt/mTOR pathway. Methods: MiR-223 and ZIC1 expression in PC tissue and cell lines was detected. PANC-1 cells and SW1990 cells were screened for subsequent experiments. Screened cells were transfected with miR-223- or ZIC1-related  oligonucleotides or plasmids, or AZD8055, the dual inhibitor of the PI3K/Akt/mTOR signaling pathway to test the functions of miR-223, ZIC1 or PI3K/Akt/mTOR signaling pathway in the biological functions of PC cells. The expression of miR-223, ZIC1, or PI3K/Akt/mTOR signaling pathway-related proteins was examined. Tumor xenograft in nude mice was conducted for the detection of tumor growth of PC. Results: Up-regulated miR-223 and declined ZIC1 existed in PC tissues of patients and cell lines. ZIC1 was determined to be a target gene of miR-223. Down-regulated miR-223 or up-regulated ZIC1 led to suppressed proliferation, migration, invasion, and cell cycle entry, volume and weight of tumors, while elevated apoptosis in PC cells through declining phosphorylation levels of PI3K, Akt and mTOR. MiR-223 up-regulation or ZIC1 down-regulation induced opposite results on PC cells. Conclusion: This study highlights that down-regulated miR-223 or elevated ZIC1 inhibits the development of PC via restricting activation of the PI3K/Akt/mTOR pathway, which has important meanings for exploring the mechanism of PC.

5.
World J Gastroenterol ; 26(36): 5498-5507, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33024400

RESUMO

BACKGROUND: B-mode-ultrasound-guided percutaneous cholecystostomy (PC) may be performed by a transhepatic or transperitoneal approach, called percutaneous transhepatic gallbladder drainage (PHGD) and percutaneous transperitoneal gallbladder drainage (PPGD), respectively. We compared the impact of PC related to the route of catheter placement on subsequent laparoscopic cholecystectomy (LC). AIM: To compare the impact of PC related to the route of catheter placement on subsequent LC. METHODS: We retrospectively studied 103 patients with acute calculous cholecystitis who underwent scheduled LC after PC between January 2010 and January 2019. Group I included 58 patients who underwent scheduled LC after PHGD. Group II included 45 patients who underwent scheduled LC after PPGD. Clinical outcomes were analyzed according to each group. RESULTS: Baseline demographic characteristics did not differ significantly between both groups (P > 0.05). Both PHGD and PPGD were able to quickly resolve cholecystitis sepsis. Group I showed significantly higher efficacy than group II in terms of lower pain score during puncture (3.1 vs 4.5; P = 0.001) and at 12 h follow-up (1.5 vs 2.2; P = 0.001), lower rate of fever within 24 h after PC (13.8% vs 42.2%; P = 0.001), shorted operation duration (118.3 vs 139.6 min; P = 0.001), lower amount of intraoperative bleeding (72.1 vs 109.4 mL; P = 0.001) and shorter length of hospital stay (14.3 d vs 18.0 d; P = 0.001). However, group II had significantly lower rate of local bleeding at the PC site (2.2% vs 20.7%; P = 0.005) and lower rate of severe adhesion (33.5% vs 55.2%; P = 0.048). No significant differences were noted between both groups regarding the conversion rate to laparotomy, rate of subtotal cholecystectomy, complications and pathology. CONCLUSION: B-mode-ultrasound-guided PHGD is superior to PPGD followed by LC for treatment of acute calculous cholecystitis, with shorter operating time, minimal amount of intraoperative bleeding and short length of hospital stay.

6.
Cell Transplant ; 29: 963689720963936, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33028108

RESUMO

We have previously reported that miR-9 promotes the homing, proliferation, and angiogenesis of endothelial progenitor cells (EPCs) by targeting transient receptor potential melastatin 7 via the AKT autophagy pathway. In this way, miR-9 promotes thrombolysis and recanalization following deep vein thrombosis (DVT). However, the influence of miR-9 on messenger RNA (mRNA) expression profiles of EPCs remains unclear. The current study comprises a comprehensive exploration of the mechanisms underlying the miR-9-regulated angiogenesis of EPCs and highlights potential treatment strategies for DVT. We performed RNA sequence analysis, which revealed that 4068 mRNAs were differentially expressed between EPCs overexpressing miR-9 and the negative control group, of which 1894 were upregulated and 2174 were downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these mRNAs were mainly involved in regulating cell proliferation/migration processes/pathways and the autophagy pathway, both of which represent potential EPC-based treatment strategies for DVT. Reverse transcriptase quantitative polymerase chain reaction confirmed the changes in mRNA expression related to EPC angiogenesis, migration, and autophagy. We also demonstrate that miR-9 promotes EPC migration and angiogenesis by regulating FGF5 directly or indirectly. In summary, miR-9 enhances the expression of VEGFA, FGF5, FGF12, MMP2, MMP7, MMP10, MMP11, MMP24, and ATG7, which influences EPC migration, angiogenesis, and autophagy. We provide a comprehensive evaluation of the miR-9-regulated mRNA expression in EPCs and highlight potential targets for the development of new therapeutic interventions for DVT.

7.
Nanoscale Horiz ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052993

RESUMO

Potassium ion hybrid capacitors (KIHCs) have drawn growing interest owing to their outstanding energy density, power density and excellent cycling stability. However, the large ionic radius of potassium triggers a huge volume change during continuous K+ insertion/extraction processes, restricting the development of KIHCs. Here, we report N-doped carbon nanotubes (NCNTs) for high-performance K+ storage. The NCNTs possess a hierarchical structure and N functional groups and not only offer sufficient space to relieve the volume expansion, but also provide highly efficient channels to transport electrons and ions. As a result, the NCNTs anode presents a high specific capacity and an excellent cycling stability with an average decay rate of 0.0238% per cycle (the lowest value among the reported carbon-based anodes for K-ions batteries) during 3600 continuous cycles. A potassium ion hybrid capacitor (KIHC) was also designed with the NCNT anode and a commercial active carbon cathode and achieved both a high energy/power density (117.1 W h kg-1/1713.4 W kg-1) and a long cycle life (2000 cycles at 1 A g-1). Moreover, the in situ Raman and ex situ element mapping characterization demonstrate the outstanding electrochemical reversibility of the NCNTs. This work provides a superior strategy to design low-cost anode materials with excellent K+ storage electrochemistry.

8.
Elife ; 92020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064077

RESUMO

In plants, establishment of de novo DNA methylation is regulated by the RNA-directed DNA methylation (RdDM) pathway. RdDM machinery is known to concentrate in the Cajal body, but the biological significance of this localization has remained elusive. Here, we show that the antiviral methylation of the Tomato yellow leaf curl virus (TYLCV) genome requires the Cajal body in Nicotiana benthamiana cells. Methylation of the viral genome is countered by a virus-encoded protein, V2, which interacts with the central RdDM component AGO4, interfering with its binding to the viral DNA; Cajal body localization of the V2-AGO4 interaction is necessary for the viral protein to exert this function. Taken together, our results draw a long sought-after functional connection between RdDM, the Cajal body, and antiviral DNA methylation, paving the way for a deeper understanding of DNA methylation and antiviral defences in plants.

9.
Mikrochim Acta ; 187(11): 612, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064202

RESUMO

This review (with 106 references) summarizes the latest progress in the synthesis, properties and biomedical applications of gold nanotubes (AuNTs). Following an introduction into the field, a first large section covers two popular AuNTs synthesis methods. The hard template method introduces anodic alumina oxide template (AAO) and track-etched membranes (TeMs), while the sacrificial template method based on galvanic replacement introduces bimetallic, trimetallic AuNTs and AuNT-semiconductor hybrid materials. Then, the factors affecting the morphology of AuNTs are discussed. The next section covers their unique surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS) and their catalytic properties. This is followed by overviews on the applications of AuNTs in biosensors, protein transportation, photothermal therapy and imaging. Several tables are presented that give an overview on the wealth of synthetic methods, morphology factors and biological application. A concluding section summarizes the current status, addresses current challenges and gives an outlook on potential applications of AuNTs in biochemical detection and drug delivery.Graphical abstract.

10.
Mol Plant ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32927102

RESUMO

The 5-methylcytosine DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1)-mediated active DNA demethylation is critical for shaping the genomic DNA methylation landscape in Arabidopsis. Whether and how the stability of ROS1 may be regulated by post-translational modifications is unknown. Using a methylation-sensitive PCR (CHOP-PCR)-based forward genetic screen for Arabidopsis DNA hyper-methylation mutants, we identified the SUMO E3 ligase SIZ1 as a critical regulator of active DNA demethylation. Dysfunction of SIZ1 leads to hyper-methylation at approximately 1000 genomic regions. SIZ1 physically interacts with ROS1 and mediates the SUMOylation of ROS1. The SUMOylation of ROS1 is reduced in siz1 mutant plants. Compared with that in wild-type plants, the protein level of ROS1 is significantly decreased, whereas there is an increased level of ROS1 transcripts in siz1 mutant plants. Our results suggest that SIZ1-mediated SUMOylation of ROS1 promotes its stability and positively regulates active DNA demethylation.

11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 197-201, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981271

RESUMO

Objective: To investigate the effects of leptin on glucose metabolism and related inflammatory factors in diabetic rats. Methods: Ten healthy male Wistar rats were randomly selected as the control group. Fifty rats were fed with high sugar and high fat diet and injected with streptozotocin (STZ, 25 mg/kg) intraperitoneally. They were randomly divided into model group, leptin low, middle and high dose group. The rats in the low, middle and high dose group were fed with leptin at the doses of 20, 50 and 100 µg/kg for 5 d respectively. Blood glucose (FBG) was measured by GOD-PAP method, insulin content (INS) was tested by radioimmunoassay, the serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL-C) and high density lipoprotein (HDL-C) were determined by automatic biochemical analyzer, the contents of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the expression of leptin in adipose tissue of diabetic rats. Results: Compared with the control group, the blood glucose levels of other groups were increased significantly (P<0.01). Compared with the model group, the blood glucose levels of middle and high dose leptin rats decreased significantly (P<0.05, P<0.01). The insulin level of high dose leptin group decreased significantly (P<0.01). There was no significant difference in FBG and INS among the three groups (P>0.05). Compared with the model group, TC levels of middle and high dose leptin group were decreased significantly (P<0.05, P<0.01). TG and LDL-C levels of high dose leptin group were decreased significantly (P<0.05), HDL-C level of high dose group was increased significantly (P<0.01). Compared with different dose groups, the high dose of leptin (100 µg/kg) could decrease the levels of TC, TG and LDL-C, and increase the level of HDL-C, which was better than those of the middle and low dose of leptin (P<0.05) Compared with the model group (52.27±10.93), the levels of leptin in low, middle and high dose group were (47.35±12.09), (44.68±10.23) and (40.13±9.87) respectively, which could be decreased by leptin in a dose-dependent manner. Conclusion: The abnormal secretion of leptin is one of the factors inducing diabetes mellitus. Under the intervention of a certain concentration of exogenous leptin (100 µg/kg), it can significantly reduce the level of MDA, TNF-α, and improve the level of IL-6. The mechanism may be closely related to the reduction of inflammatory response, oxidative stress and correction of dyslipidemia. Leptin also reduces the risk of disease progression in diabetes treatment.

12.
Int Orthop ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915285

RESUMO

PURPOSE: The purpose of this study was to evaluate changes of patellar height and posterior tibial slope angle following uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy. METHODS: All patients who underwent uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy between January 2017 and February 2019 were included and assessed retrospectively. Radiological assessment was made in terms of the changes in patellar height and posterior tibial slope angle between pre-operative and post-operative radiographs. RESULTS: Thirty-five patients (9 males and 26 females) with a mean age of 57.3 years (range 50.8-64.2 years) were enrolled in this study protocol and demonstrated decreased posterior tibial slope angle post-operatively (9.7° ± 2.5° pre-operatively and 7.3° ± 1.8° post-operatively, P < 0.001). Patellar height was unchanged significantly post-operatively (Caton-Deschamps: 0.83 ± 0.12 pre-operatively and 0.82 ± 0.09 post-operatively, P > 0.05). CONCLUSIONS: Uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy can decrease posterior tibial slope and maintain the patellar height.

13.
Theranostics ; 10(21): 9443-9457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863938

RESUMO

Objective: Esophageal squamous cell carcinoma (ESCC) is one of the most commonly diagnosed cancer types in China. Recent genomic sequencing analysis indicated the over-activation of Hippo/YAP signaling might play important roles for the carcinogenic process and progression for ESCC patients. However, little is known about the molecular mechanisms that controls Hippo signaling activity in ESCC. Our previous studies indicated that PLCE1-an important risk factor for ESCC-linked to ESCC progression through snail signaling, during this period, we found PARK2 was an important downstream target of PLCE1-snail axis. PARK2 was decreased in ESCC human samples, and correlated with good prognosis in ESCC patients. Further research showed that PARK2 could inhibit YAP, which functions as key downstream effectors of the Hippo pathway. Here, we aim to reveal the molecular mechanisms of PARK2 modulated Hippo pathway in ESCC. Methods: To evaluate the function of PARK2 in ESCC, we used a tissue microarray (TMA) of 223 human ESCC patients and immunohistochemistry to analyze the correlation between PARK2 expression and clinicopathologic variables. Depletion of endogenous PARK2 and YAP from ESCC cells using CRISPR/Cas9 technologies. Flow cytometry and EdU cell proliferation assay were used to detect proliferation of ESCC cells. Nude mice subcutaneous injection and Ki-67 staining were used to evaluate tumor growth in vivo. Migration and invasion assays were performed. In addition, lung metastasis models in mice were used to validate the function of PARK2 in vivo. Identification of PARK2 involved in hippo pathway was achieved by expression microarray screening, double immunofluorescence staining and co-immunoprecipitation assays. The RNA-seq analysis results were validated through quantitative real-time PCR (qRT-PCR) analysis. The protein half-life of YAP was analyzed by Cycloheximide assay, and the TEAD activity was detected by Luciferase reporter assays. Results: Clinical sample of ESCC revealed that low PARK2 expression correlated with late tumor stage (P < 0.001), poor differentiation (P < 0.04), lymph node (P < 0.001) and distant metastasis (P = 0.0087). Multivariate Cox proportional regression analysis further revealed that PARK2 expression (P = 0.032) is an independent prognostic factor for the overall survival of ESCC patients. Besides, the immunohistochemistry results showed that PARK2 negatively correlated with YAP protein level (P < 0.001). PARK2 depletion promotes ESCC progression both through Hippo/YAP axis, while PARK2 overexpression suppresses ESCC tumor progression by Hippo signaling. Co-IP and ubiquitination assays revealed that PARK2 could interact with YAP in the cytosol and promotes YAP K48-linked ubiquitination at K90 sites. Conclusion: Clinical sample analysis and mechanistic study have validated PARK2 as a tumor suppressor for ESCC. Multivariate Cox proportional regression analysis further revealed that PARK2 is an independent prognostic factor for the overall survival of ESCC patients. Cellular and molecular mechanisms in this study showed that PARK2 associated with YAP protein in the cytosol, promoted YAP ubiquitination and proteasome-dependent degradation in ESCC cells. Therefore, as a novel modulator for Hippo signaling, modulation of PARK2 activity or gene expression level could be an appealing strategy to treat esophageal.

14.
Zhongguo Zhen Jiu ; 40(8): 816-20, 2020 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-32869588

RESUMO

OBJECTIVE: To observe the effect of ginger-separated moxibustion on fatigue, sleep quality and depression in the patients with chronic fatigue syndrome. METHODS: A total of 62 patients with chronic fatigue syndrome were randomized into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). In the control group, the patients had normal diet and proper physical exercise. In the observation group, on the basis of the control group, the ginger-separated moxibustion was added at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every two days, 3 times weekly. Separately, before treatment and after 4 weeks of treatment, the MOS item short form health survey (SF-36), the Pittsburgh sleep quality index (PSQI) scale and the self-rating depression scale (SDS) were adopted to evaluate the degrees of fatigue, sleep quality and depression in the patients of the two groups. RESULTS: In the observation group, the score of each item of SF-36, the score of each item of PSQI and SDS score after treatment were all improved significantly as compared with those before treatment respectively (P<0.05, P<0.01). In the control group, the scores of overall health, vitality and mental health in SF-36 and the score of sleep time of PSQI after treatment were improved as compared with those before treatment respectively (P<0.05). After treatment, the score of each item of SF-36, the scores of sleep quality, sleep time, sleep efficiency and sleep disorders of PSQI, as well as SDS score in the observation group were all better than those in the control group respectively (P<0.01, P<0.05). The score of SF-36 was relevant to the scores of PSQI and SDS in the patients of chronic fatigue syndrome (r =0.331, P<0.05; r =-0.706, P<0.01). The improvement value of SF-36 score was closely related to the improvement value of SDS score in the observation group (r =-0.657, P<0.01). CONCLUSION: The ginger-separated moxibustion effectively relieves fatigue and depression condition and improves sleep quality in the patients with chronic fatigue syndrome. The fatigue condition is relevant with sleep quality and depression condition to a certain extent in the patients.

15.
Mol Med Rep ; 22(4): 2925-2931, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945398

RESUMO

Previous studies have suggested that pathogenic variants in interferon regulatoryse factor 6 (IRF6) can account for almost 70% of familial Van der Woude Syndrome (VWS) cases. However, gene modifiers that account for the phenotypic variability of IRF6 in the context of VWS remain poorly characterized. The aim of this study was to report a family with VWS with variable expressivity and to identify the genetic cause. A 4­month­old boy initially presented with cleft palate and bilateral lower lip pits. Examination of his family history identified similar, albeit milder, clinical features in another four family members, including bilateral lower lip pits and/or hypodontia. Peripheral blood samples of eight members in this three­generation family were subsequently collected, and whole­exome sequencing was performed to detect pathogenic variants. A heterozygous missense IRF6 variant with a c.1198C>T change in exon 9 (resulting in an R400W change at the amino acid level) was detected in five affected subjects, but not in the other three unaffected subjects. Moreover, subsequent structural analysis was indicative of damaged stability to the structure in the mutant IRF protein. Whole­transcriptome sequencing, expression analysis and Gene Ontology enrichment analysis were conducted on two groups of patients with phenotypic diversity from the same family. These analyses identified significant differentially expressed genes and enriched pathways in these two groups. Altogether, these findings provide insight into the mechanism underlying the variable expressivity of VWS.

16.
Med Sci Monit ; 26: e920956, 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32892204

RESUMO

BACKGROUND The study aimed to explore the genetic association of Fc receptor-like 5 (FCRL5) gene variants (rs6427384 and rs6692977) with ankylosing spondylitis risk in Chinese Han population. MATERIAL AND METHODS Genotyping for FCRL5 gene variations rs6427384 and rs6692977 was implemented among 130 ankylosing spondylitis cases and 135 healthy persons, through polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Frequency dissimilarity for 2 polymorphisms was compared between 2 groups using chi-square test. The association strength of FCRL5 gene polymorphism with ankylosing spondylitis risk was estimated by odds ratios with 95% confidence intervals. RESULTS The frequencies of rs6427384 CC genotype and C allele were significantly lower in the case group than that in the control group (P<0.05), which suggested that C allele of rs6427384 polymorphism might offer protection against ankylosing spondylitis onset. Whereas only 2 genotypes of rs6692977 were detected in the control group, and no significant association was found with ankylosing spondylitis susceptibility. CONCLUSIONS FCRL5 gene polymorphism rs6427384 was correlated to ankylosing spondylitis occurrence among Chinese Han population, while rs6692977 was not.

18.
Oncogene ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973333

RESUMO

ERα positive breast cancer accounts for 70% of breast malignancies. Compared with ERα negative types, ERα positive breast cancer could be effective controlled by endocrine therapy. However, more than half of the patients will develop endocrine resistance, making it an important clinical issue for breast cancer therapy. Endocrine resistance might be caused by multiple alternations, including the components of ERα signaling, during tumor progression. Thus, it is urgent and necessary to uncover the molecular mechanisms that controls ERα expression and stability to improve breast cancer therapeutics. In our current study, we identifies that the ubiquitin ligase RNF181 stabilizes ERα and facilitates breast cancer progression. The expression of RNF181 is correlated with ERα level in human breast tumors and relates to poor survival in endocrine-treated patients. RNF181 depletion inhibits breast cancer progression in vivo and in vitro, reduces ERα protein level and its target gene expression, such as PS2 and GREB1. Unbiased RNA sequencing analysis indicates RNF181 is necessary for ERα signature gene expression in whole genomic level. Immuno-precipitation assays indicate that RNF181 associates with ERα and promotes its stability possibly via inducing ERα K63-linked poly-ubiquitination. In conclusion, our data implicate a non-genomic mechanism by RNF181 via stabilizing ERα protein controls ERα target gene expression linked to breast cancer progression.

19.
Mol Med Rep ; 22(5): 3777-3784, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32901864

RESUMO

The aim of the present study was to use the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR­associated (Cas) 9­mediated gene knockout technology for the rapid classification of the differential function of micro (mi)RNAs screened using miRNA expression profiling by microarray. The rational design of single guide RNAs for the CRISPR/Cas9 system was verified to function in human LNCaP cells with rapid and efficient target gene editing. miRNA (miR)­205, miR­221, miR­222, miR­30c, miR­224, miR­455­3p, miR­23b and miR­505 were downregulated in patients with prostate cancer (PCa) and were experimentally validated to function as tumor suppressors in prostate cancer cells, affecting tumor proliferation, invasion and aerobic glycolysis. In addition, the data of the present study suggested that miR­663a and mfiR­1225­5p were upregulated in prostate cancer tissues and cell proliferation of miR­663a and miR­1225­5p knockout PCa cells was significantly lower compared with miR­NC cells. Furthermore, knockout of miR­1225­5p and miR­663a significantly decreased the lactate production in LNCaP cells in vitro. In conclusion, the present study offered a simple and efficient method for rapidly classifying miRNA function by applying CRISPR/Cas9 in LNCaP cells. The present study suggested, for the first time to the best of the authors' knowledge, that the aberrant expression of miR­663a and miR­1225­5p may be involved with the progression of prostate cancer, implying their potential as candidate markers for this type of cancer. However, the precise role of miR­663a and miR­1225­5p in accelerating the development of prostate cancer and promoting tumor progression remains to be elucidated.

20.
Brain Res Bull ; 164: 269-288, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32916221

RESUMO

10-O-(N, N-dimethylaminoethyl) ginkgolide B methanesulfonate (XQ-1H), a novel analog of ginkgolide B, has been preliminarily recognized to show bioactivities against ischemia-induced injury. However, the underlying mechanism still remains to be fully elucidated. The aim of this study was to investigate the effect of XQ-1H against cerebral ischemia/reperfusion injury (CIRI) from the perspective of blood brain barrier (BBB) protection, and explore whether the underlying mechanism is associated with Wnt/GSK3ß/ß-catenin signaling pathway activation. The therapeutic effects of XQ-1H were evaluated in mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and in immortalized mouse cerebral endothelial cells (bEnd.3) challenged by oxygen and glucose deprivation/reoxygenation (OGD/R). Results showed that treatment with XQ-1H improved neurological behavior, reduced brain infarction volume, diminished edema, and attenuated the disruption of BBB in vivo. In vitro, XQ-1H increased cell viability and maintained the barrier function of bEnd.3 monolayer after OGD/R. Moreover, the protection of XQ-1H was accompanied with activation of Wnt/GSK3ß/ß-catenin pathway and upregulation of tight junction proteins. Notably, the protection of XQ-1H was abolished by Wnt/GSK3ß/ß-catenin inhibitor XAV939 or ß-catenin siRNA, indicating XQ-1H exerted protection in a Wnt/GSK3ß/ß-catenin dependent profile. In summary, XQ-1H attenuated brain injury and maintained BBB integrity after CIRI, and the possible underlying mechanism may be related to the activation of Wnt/GSK3ß/ß-catenin pathway and upregulation of tight junction proteins.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA