Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 936
Filtrar
2.
J Biopharm Stat ; : 1-9, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32394789

RESUMO

Raw materials for traditional Chinese medicine (TCM) are often from different resources and its final product may also be made by different sites. Therefore, variabilities from different resources such as site-to-site or within site component-to-component may be expected. Consequently, test for consistency in raw materials, in-process materials, and/or final product has become an important issue in the quality control (QC) process in TCM development. In this paper, a statistical QC process for raw materials and/or the final product of TCM is proposed based on a two sided [Formula: see text]-content, [Formula: see text]-confidence tolerance interval. More specifically, we construct the tolerance interval for a random-effects model to assess the QC of TCM products from different regions and possibly different product batches. The products can be claimed to be consistency when the constructed tolerance interval is within the permitted range. Given the region and batch effects, sample sizes can also be calculated to ensure the desired measure of goodness. An example is presented to illustrate the proposed approach.

3.
Mol Med Rep ; 22(1): 51-56, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377721

RESUMO

MicroRNA (miR)-19b is expressed in various types of tumors and may serve as a potential therapeutic target. The miR­17­92 cluster is upregulated in nasopharyngeal carcinoma (NPC) tissues and cells. miR­19b is a member of the miR­17­92 cluster; however, its expression and function in NPC are largely unknown. The present study aimed to investigate the expression and function of miR­19b in NPC cells. The miRCURY LNATM miRNA Inhibitor (miR­19b inhibitor and negative control) were transfected into C666­1 cells. The proliferation, apoptosis and migration of the cells were subsequently detected by the Cell Counting Kit­8 assay, flow cytometry and Transwell assay, respectively. Additionally, the expression of STAT3 signaling pathway­associated proteins [STAT3, pSTAT3 and suppressor of cytokine signaling 1 (SOCS1)] and the transcriptional targets of pSTAT3 [Bcl­2, myeloid leukemia protein 1 (Mcl­1) and cyclin D1] were detected by western blotting. The miR­19b inhibitor inhibited proliferation and migration and induced apoptosis of C666­1 cells. Furthermore, the miR­19b inhibitor upregulated the expression of SOCS1, a predicted target gene of miR­19b, and decreased the phosphorylation of STAT3 at Tyr705 and Ser727. These data indicated that upregulation of SOCS1, an endogenous inhibitor of STAT3 phosphorylation, attenuated the STAT3 signaling pathway in C666­1 cells. Moreover, the expression level of the proproliferative protein cyclin D1 and antiapoptotic proteins Mcl­1 and Bcl­2 was significantly decreased following transfection with the miR­19b inhibitor. The aforementioned three proteins are downstream transcriptional targets of the activated STAT3 signaling pathway. The results of the present study revealed that inhibition of miR­19b negatively modulated the malignant behavior of NPC cells via the STAT3 signaling pathway. Therefore, miR­19b inhibition may serve as a novel therapeutic target for the treatment of NPC.

4.
Int J Clin Pract ; : e13534, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32418282

RESUMO

BACKGROUND: As the Chinese population continues to age, the incidence of neurodegenerative diseases (NDDs) has increased dramatically, which results in heavy medical and economic burden for families and society. OBJECTIVE: The objective of this study was to evaluate NDDs in a southern Chinese hospital over a 10-year period and examine trends in demographics, outcome, length of stay, and cost. METHODS: Retrospective medical records of patients from January 2010 to December 2019 were collected, including 7231 patients with NDDs (as case group) and 9663 patients without any NDDs (as control group). The information of social demographic data, admission source, reasons for admission, outcomes, length of stay (LOS), and cost were extracted and analyzed. RESULT: The average hospitalization age of the patients with NDDs is over 65 years (peak age 70-89 years). Compared to the control group, the case group had a longer LOS and a higher cost and the numbers of patients with NDDs increased yearly from 2010 to 2019. The LOS shortened while the cost increased. Clinical features affected LOS and cost. Patients suffering from infection, abnormal blood pressure and the imbalance of water-electrolyte homeostasis as main reasons for admission were decreased; however, heart disease, cerebrovascular accident and mental diseases were significantly increased, the overall change trend of fracture/trauma remained stable. The rate of discharge to home care and mortality declined; discharge to other medical or community facilities increased over ten years. CONCLUSION: The majority of NDDs patients tended to be older. During the last 10 years from 2010 to 2019, the numbers of NDDs patients increased yearly, the trend of LOS became shortening and the cost gradually increasing. The main reasons of admission and outcomes of hospital showed different trends.

5.
J Dig Dis ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32378783

RESUMO

BACKGROUND: The performance of digestive doctors to diagnose the traditional Chinese medicine (TCM) syndrome of functional dyspepsia (FD) is unknown in China. The aim of the study was to compare the diagnostic agreement of TCM syndromes of FD, including postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) between the digestive doctors and TCM practitioners. METHODS: Patients with PDS or EPS were enrolled in six tertiary referral centers between January 2016 and December 2017. The TCM syndromes of the patients were first diagnosed by digestive doctors who performed TCM differential diagnosis based on the main symptoms. The TCM practitioners further diagnosed the TCM syndrome types of enrolled patients. The agreement of diagnosis between the digestive doctors and TCM practitioners was calculated. The demographic data and composition of TCM syndrome types were collected and analyzed. RESULTS: 160 patients including 81 PDS and 79 EPS were enrolled in this study. The total diagnosis consistency rate between the digestive doctors and TCM practitioners was 86.3%. The diagnosis consistency rate of PDS and EPS was 87.3% and 85.2%, respectively. The most common TCM syndrome type of PDS was liver-stomach disharmony syndrome (33.3%) and spleen-deficiency and Qi-stagnation syndrome (33.3%), while that for EPS was liver-stomach disharmony syndrome (36.7%). CONCLUSIONS: Digestive doctors had a high diagnostic agreement regarding the TCM syndrome types of FD based on the main symptoms differential diagnosis as compared to the TCM practitioners. This would aid the digestive doctors while selecting the Chinese patent medicine for FD based on syndrome differentiation. This article is protected by copyright. All rights reserved.

6.
Neurochem Res ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32383026

RESUMO

Translocator protein 18 kDa (TSPO) is mainly distributed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. It mediates cholesterol transportation across the phospholipid membrane, which is a prerequisite for neurosteroid synthesis. Though the ligand of TSPO has clinical value in the diagnosis and treatment of neuropsychiatric disorders, the pharmacological study of TSPO for anti-postpartum depression has not been reported. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). The effect of YL-IPA08, a new ligand compound of TSPO, on PPD was evaluated using multiple behavioral tests at progressive time points. Additionally, real-time quantitative PCR, Western-blotting and an enzyme linked immunosorbent assay were conducted to elucidate the potential molecular mechanism of such effect. We report that the levels of TSPO and neurosteroids in the hippocampus and prefrontal cortex were significantly decreased in PPD rats compared to healthy controls. After 3 weeks of drug treatment, the levels of TSPO and neurosteroids in the hippocampus of PPD rats were increased, and anxiety and depressive like behaviors were alleviated. Meanwhile, compared with sertraline treatment, a positive control in this study, YL-IPA08 treatment had a shorter onset time. Our results suggest that the anxiolytic and anti-depressive activity of YL-IPA08 has significant value in the treatment of PPD and that TSPO may be a potential new target for the treatment of PPD.

7.
Int J Infect Dis ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32439540

RESUMO

OBJECTIVES: To better understand the spectrums of pathogens causing herpangina and circulation of Coxsackievirus A4 in Yancheng, China. METHODS: Stool samples from herpangina and HFMD cases were collected. Real Time PCR Kits was used to identify Enterovirus 71, CV-A16 and CV-A6, and nested reverse transcription PCR (nRT-PCR) to detect the other enterovirus types. Complete VP1 and genome sequence of CV-A4 were amplified by using nRT-PCR. Genetic, phylogenetic and recombination analysis were performed. RESULTS: Co-circulation of three recombinant CV-A4 groups, including one novel (C2 lineage), was identified in Yancheng, China, 2016 and 2018. One was the major causative agent of herpangina, and another two were responsible for HFMD. Phylogenetic and recombination analysis indicated that the non-structural region of their genome originated from the same ancestry and subsequently adaptation. C2 lineage of CV-A4 group may be introduced from countries outside China and its genome occurred recombination in China. CONCLUSION: Novel recombinant CV-A4 was mainly associated with herpanginain in Yancheng, 2018, China. C2 lineage of CV-A4 group with recombinant non-structural region was also identified in HFMD patients.

8.
Gene ; : 144779, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428697

RESUMO

In insects, nuclear receptors (NRs) including EcR (NR1H1), USP (NR2B4), E75 (NR1D3), HR3 (NR1F), HR4 (NR6) and FTZ-F1 (NR5A3) mediate the 20-hydroxyecdysone (20E) signaling cascade to play a critical role during larval metamorphosis. In this present paper, we focused on hormone receptor 38 (HR38) in Leptinotarsa decemlineata, the only insect homolog of the NR4A subclass. RNA interference (RNAi) of LdHR38 in the penultimate (third) instar larvae reduced the expression of an ecdysteroidogenesis gene and declined the titer of 20E. Knockdown of LdHR38 intensified the expression of LdUSP, LdE75, LdE74, LdE93, LdBroad and LdHR3, whereas repressed the transcription of LdFTZ-F1. Disruption of 20E signaling inhibited chitin biosynthesis in the larval cuticle. Approximately 25% of the LdHR38 RNAi larvae died, around 40% of the resultant larvae remained as prepupae or become deformed pupae. The body surface of the HR38 depleted abnormal prepupae and pupae looked wet, just like the cuticle being covered with a layer of liquid. Moreover, the increase of larval mortality, and the impairment of pupation and emergence exhibited dose-dependent manners. Furthermore, silencing LdHR38 at the final (fourth) instar caused similar but less severe impairment of pupation. Dietary supplement with 20E for the third instar larvae did not rescue the high larval death and only slightly alleviated the low pupation rate in the LdHR38 RNAi hypomorphs. Accordingly, we propose that HR38 is necessary for tune of ecdysteroidogenesis and for mediation of 20E signaling during metamorphosis in L. decemlineata.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32274508

RESUMO

OBJECTIVES: To investigate the prevalence and transmission of mcr-3 among Salmonella enterica serotype Typhimurium and 1,4,[5],12:i:-. METHODS: A total of 4724 clinical Salmonella isolates were screened for the presence of mcr-3 in China during 2014-19. The clonal relationship of the mcr-3-positive isolates and their plasmid contents and complete sequence were also characterized based on WGS data from the Illumina and MinION platforms. RESULTS: We identified 10 mcr-3-positive isolates, and all were MDR, mostly resistant to colistin, cefotaxime, ciprofloxacin, doxycycline and florfenicol. mcr-3 was co-present with blaCTX-M-55-qnrS1 on hybrid ST3-IncC-FII conjugatable plasmids (n = 6) and an ST3-IncC non-conjugatable plasmid (n = 1) and embedded into a pCHL5009T-like IncFII plasmid on the Salmonella chromosome (n = 3). Four distinctive genetic contexts surrounded mcr-3 and all but one were closely related to each other and to the corresponding region of IncFII plasmid pCHL5009T. IS15DI was most likely the vehicle for integration of mcr-3-carrying IncFII plasmids into ST3-IncC plasmids and the chromosome and for shaping the MDR regions. In addition, a phylogenetic tree based on the core genome revealed a unique Salmonella lineage (≤665 SNPs) that contained these 10 mcr-3-positive isolates and another 38 (33 from patients) mcr-3-positive Salmonella from five countries. In particular, most of the 51 mcr-3-positive isolates belonged to ST34 and harboured diverse antibiotic resistance genes (ARGs), including mcr-3-blaCTX-M-55-qnrS1, and possessed similar ARG profiles. CONCLUSIONS: Our findings revealed global clonal spread of MDR ST34 Salmonella from clinical isolates co-harbouring mcr-3 with blaCTX-M-55 and qnrS1 and a flexibility of mcr-3 co-transmittance with other ARGs mediated by mobile genetic elements.

10.
Cancer Lett ; 482: 8-18, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32278815

RESUMO

Hepatocellular carcinoma (HCC), a type of malignant liver tumor, has a grim prognosis. As a functional protein, synaptopodin-2 (SYNPO2) has been associated with malignancy; however, the expression profile and function of SYNPO2 in HCC remains unknown. Herein, we revealed that SYNPO2 was transcriptionally downregulated in HCC tissues from both The Cancer Genome Atlas cohort and our cohort, and was also decreased at the translational level as determined by western blotting and immunohistochemical staining. Furthermore, reduced SYNPO2 expression correlated significantly with short overall survival and recurrence free survival of HCC patients. Restoring SYNPO2 expression inhibited the proliferation and aggressiveness of hepatocarcinoma cells. Mechanistically, increasing the ratio of cytoplasmic SYNPO2 to nuclear SYNPO2 was positively associated with recurrence rate in HCC patients; calcineurin (CaN) activity positively correlated with cytoplasmic SYNPO2 levels in HCC tissues; and nuclear-cytoplasmic translocation of SYNPO2 was induced by CaN to facilitate metastasis of HCC through assembly of peripheral actin bundles. In short, our findings uncover a novel role of SYNPO2 in HCC metastasis via the CaN/SYNPO2/F-actin axis, and indicate that SYNPO2 may serve as a possible prognostic marker and novel therapeutic target.

11.
Stem Cell Res Ther ; 11(1): 153, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32272974

RESUMO

BACKGROUND: To date, it has repeatedly been demonstrated that infusing bone marrow-derived stem cells (BMSCs) into acellular nerve scaffolds can promote and support axon regeneration through a peripheral nerve defect. However, harvesting BMSCs is an invasive and painful process fraught with a low cellular yield. METHODS: In pursuit of alternative stem cell sources, we isolated stem cells from the inguinal subcutaneous adipose tissue of adult Sprague-Dawley rats (adipose-derived stem cells, ADSCs). We used a co-culture system that allows isolated adult mesenchymal stem cells (MSCs) and Schwann cells (SCs) to grow in the same culture medium but without direct cellular contact. We verified SC phenotype in vitro by cell marker analysis and used red fluorescent protein-tagged ADSCs to detect their fate after being injected into a chemically extracted acellular nerve allograft (CEANA). To compare the regenerative effects of CEANA containing either BMSCs or ADSCs with an autograft and CEANA only on the sciatic nerve defect in vivo, we performed histological and functional assessments up to 16 weeks after grafting. RESULTS: In vitro, we observed reciprocal beneficial effects of ADSCs and SCs in the ADSC-SC co-culture system. Moreover, ADSCs were able to survive in CEANA for 5 days after in vitro implantation. Sixteen weeks after grafting, all results consistently showed that CEANA infused with BMSCs or ADSCs enhanced injured sciatic nerve repair compared to the acellular CEANA-only treatment. Furthermore, their beneficial effects on sciatic injury regeneration were comparable as histological and functional parameters evaluated showed no statistically significant differences. However, the autograft group was roundly superior to both the BMSC- or ADSC-loaded CEANA groups. CONCLUSION: The results of the present study show that ADSCs are a viable alternative stem cell source for treating sciatic nerve injury in lieu of BMSCs.

12.
Invest Ophthalmol Vis Sci ; 61(4): 43, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32343786

RESUMO

Purpose: To evaluate episcleral vasculature in corneal limbus with optical coherence tomography angiography (OCTA) in normal controls, port-wine stain (PWS) patients, and Sturge-Weber syndrome (SWS) patients. Methods: Unilateral eyes from 18 normal controls (25.41 ± 4.00 years), 16 PWS patients (21.35 ± 11.05 years), and 8 SWS patients with ipsilateral late-onset glaucoma (22.13 ± 7.82 years). Each subject underwent slit-lamp examination, applanation tonometry, and OCTA. All OCTA scans were performed using an OCTA system operating at a wavelength of 1050-nm in four quadrants (superior, inferior, nasal, and temporal). The scans were delineated into conjunctival and episcleral layers using IMAGEnet6 for analysis. Results: Slit-lamp and OCTA images demonstrated dense dilated episcleral vessels in PWS and SWS patients, particularly in the SWS group. The mean limbal involvements of episcleral vascular anomalies under slit lamp were respectively 0.00 ± 0.00, 5.44 ± 2.92, and 8.88 ± 2.70 clock hours in the control, PWS, and SWS groups (F = 58.46, P < 0.01). Quantitative analysis of OCTA scans showed that the episcleral vessel density in controls, PWS, and SWS groups were 25.03% ± 1.47%, 28.28% ± 1.96%, and 33.59% ± 3.00%, respectively (F = 18.17, P < 0.01). We also observed higher episcleral vessel diameter index in the SWS and PWS groups in comparison with the controls, particularly in the SWS group (P < 0.01). The vessel measurements, including density and diameter, were significantly correlated with the increased IOP and cup-to-disc (C/D) in SWS patients (P < 0.01). Conclusions: To our knowledge, this is the first demonstration of OCTA in PWS and SWS patients and represents direct pathoanatomic evidence for episcleral alterations in SWS patients. The episcleral vessel measurements correlated with the increased IOP and C/D in SWS patients, indicating the episcleral vascular hypertrophy may be a risk factor for glaucoma in adult SWS patients.

13.
Hepatology ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343849

RESUMO

Hepatic ischemia-reperfusion (I/R) injury, which mainly involves inflammatory responses and apoptosis, is a common cause of organ dysfunction in liver transplantation. As a critical mediator of inflammation and apoptosis in various cell types, the role of tripartite motif-containing 27 (TRIM27) in hepatic I/R injury remains undetermined. This study systemically evaluated the putative role of TRIM27- TGF-ß-activated kinase 1 (TAK1)-JNK/p38 signaling in hepatic I/R injury. TRIM27 expression was significantly downregulated in liver tissue from liver transplantation patients, mice subjected to hepatic I/R surgery and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Subsequently, using global Trim27 knockout mice (Trim27-KO mice) and hepatocyte-specific Trim27 transgenic mice (Trim27-HTG mice), TRIM27 functions to ameliorate liver damage, reduce the inflammatory response and prevent cell apoptosis. In parallel in vitro studies, activating TRIM27 also prevented H/R-induced hepatocyte inflammation and apoptosis. Mechanistically, TRIM27 constitutively interacted with the critical components TAK1 and TAK1 binding protein 2/3 (TAB2/3) and promoted the degradation of TAB2/3, leading to inactivation of TAK1 and the subsequent suppression of downstream JNK/p38 signaling. Conclusion: TRIM27 is a key regulator of hepatic I/R injury by mediating the degradation of TAB2/3 and the suppression of downstream TAK1-JNK/p38 signaling. TRIM27 may be a promising approach to protect the liver against I/R-mediated hepatocellular damage in transplant recipients.

14.
Clin Infect Dis ; 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32271374

RESUMO

The 2019 novel coronavirus was detected in the self-collected throat washings. Positive testing rate of throat washing was much higher than that of Nasopharyngeal swabs. Throat washing is a promising candidate for 2019-nCoV screening and monitoring due to its noninvasive and reliability.

15.
Surg Endosc ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32318804

RESUMO

BACKGROUND: Radial endoscopic ultrasound (EUS) is typically used to estimate the depth of rectal polyp invasion, however, there are no data on linear EUS in this setting and its relative accuracy compared to radial EUS. METHODS: In this prospective cohort study, 89 patients with non-pedunculated rectal polyp who underwent linear EUS or radial EUS were prospectively enrolled. The invasion depth was measured for each polyp and categorized as mucosal to shallow submucosal(SMs) or deep submucosal(SMd) invasion. Invasion measurements were compared with the final diagnosis on histopathology. RESULTS: A total of 58 patients underwent radial EUS and 31 patients underwent linear EUS examination. There were 38 lesions correctly diagnosed in the radial EUS group and 29 correctly diagnosed lesions in the linear EUS group. The diagnostic accuracy of SMd invasion for linear EUS was significantly higher than radial EUS (0.936 vs. 0.655, p = 0.003). A significant difference was also noted for specificity between the two groups (0.963 vs. 0.659, p = 0.003). Univariate analysis showed radial EUS type (OR 0.131, 95% CI 0.028-0.606, p = 0.009) to be an independent predictor for incorrect diagnosis. The area under the receiver operating curve (ROC) was 0.856 and 0.651 for linear EUS and radial EUS, respectively. It was noted that four patients underwent unnecessary surgery for radial EUS while there were no such patients in the linear EUS group. CONCLUSIONS: Linear EUS was more accurate for determining SMd invasion and contributed to the selection of appropriate treatment modalities in patients with non-pedunculated rectal polyp.

16.
BMC Genomics ; 21(1): 305, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299363

RESUMO

BACKGROUND: In citrus, genetic improvement via biotechnology is hindered by the obstacle of in vitro regeneration via somatic embryogenesis (SE). Although a few B3 transcription factors are reported to regulate embryogenesis, little is known about the B3 superfamily in citrus, and which members might be involved in SE. RESULTS: Genome-wide sequence analysis identified 72 (CsB3) and 69 (CgB3) putative B3 superfamily members in the genomes of sweet orange (Citrus sinensis, polyembryonic) and pummelo (C. grandis, monoembryonic), respectively. Genome duplication analysis indicated that segmental and tandem duplication events contributed to the expansion of the B3 superfamily in citrus, and that the B3 superfamily evolved under the effect of purifying selection. Phylogenetic relationships were well supported by conserved gene structure and motifs outside the B3 domain, which allowed possible functions to be inferred by comparison with homologous genes from Arabidopsis. Expression analysis identified 23 B3 superfamily members that were expressed during SE in citrus and 17 that may play functional roles at late SE stages. Eight B3 genes were identified that were specific to the genome of polyembryonic sweet orange compared to monoembryonic pummelo. Of these eight B3 genes, CsARF19 was found to be specifically expressed at higher levels in embryogenic callus (EC), implying its possible involvement in EC initiation. CONCLUSIONS: This study provides a genome-wide analysis of the citrus B3 superfamily, including its genome organization, evolutionary features and expression profiles, and identifies specific family members that may be associated with SE.

17.
Bioresour Technol ; 307: 123227, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32229411

RESUMO

The effects of different hypochlorite types (namely Ca(OCl)2 and NaOCl) on the waste activated sludge (WAS) anaerobic fermentation, and microbial community and activity were investigated. The results indicated that both Ca(OCl)2 and NaOCl contributed to volatile fatty acids (VFAs) production by simultaneously enhancing the solubilization, hydrolysis and acidification processes. The maximal VFAs was respectively 1379.5 (at 10 d) and 1621.5 (at 8 d) mg COD/L at the optimal dose of NaOCl and Ca(OCl)2 while it was merely 157.4 (at 6 d) mg COD/L in the control. However, the Ca(OCl)2 might affect the anaerobic process in a continuous mode while the NaOCl was relatively transient, which caused distinctive influences on the microbial structure and activity, and subsequently VFAs production in WAS fermentation systems. Moreover, Ca(OCl)2 treatments showed advantages over NaOCl on WAS dewatering and VSS reduction, implying the superiority of utilizing Ca(OCl)2 as additives for WAS disposal.


Assuntos
Microbiota , Esgotos , Ácidos Graxos Voláteis , Fermentação , Concentração de Íons de Hidrogênio , Hidrólise , Ácido Hipocloroso
18.
Mol Oncol ; 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306523

RESUMO

High-mobility group protein B1 (HMGB1) has important functions in cancer cell proliferation and metastasis. However, the mechanisms of HMGB1 function in non-small-cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the underlying mechanism of HMGB1-dependent tumor cell proliferation and NSCLC metastasis. Firstly, we found high HMGB1 expression in NSCLC and showed that HMBG1 promoted proliferation, migration, and invasion of NSCLC cells. HMGB1 could bind to SNAI1 promoter and activate the expression of SNAI1. In addition, HMGB1 could transcriptionally regulate the lncRNA RSF1-IT2. RSF1-IT2 was found to function as ceRNA, sponging miR-129-5p, which targets SNAI1. Notably, HMGB1 was also identified as a target of miR-129-5p, which indicates the establishment of a positive feedback loop. Consequently, high expression of RSF1-IT2 and SNAI1 was found to closely correlate with tumor progression in both HMGB1-overexpressing xenograft nude mice and patients with NSCLC. Taken together, our findings provide new insights into molecular mechanisms of HMGB1-dependent tumor metastasis. Components of the HMGB1-RSF1-IT2-miR-129-5p-SNAI1 pathway may have a potential as prognostic and therapeutic targets in NSCLC.

19.
J Alzheimers Dis ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32310180

RESUMO

The connection between diabetes and Alzheimer's disease (AD) is not fully determined. Hyperphosphorylation of tau protein is mediated by binding and stabilization of truncated p25 with cyclin-dependent kinase-5 (CDK5) in AD. We recently showed that diabetes-associated hyperglycemia increased the CDK5 levels to promote development of AD. Here, we examined the underlying mechanisms. Hyperglycemia and glucose intolerance were induced in rats that had received a low dose of streptozotocin (STZ) and a high fat diet (HFD). Compared to the control rats that received no STZ and normal diet-fed, the STZ + HFD rats exhibited poorer performance in the behavioral test and showed hyperacetylation of H3K9 histone on CDK5 promoter, likely resulting from upregulation of a histone acetyltransferase, GCN5. Inhibition of acetylation of H3K9 histone by a specific GCN5 inhibitor, MB3, attenuated activation of CDK5, resulting in decreased tau phosphorylation in rat brain and improved performance of the rats in the behavior test. Thus, these data suggest that diabetes may promote future development of AD through hyperacetylation of H3K9 histone on CDK5 promoter.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32291179

RESUMO

BACKGROUND: HMex-3A, an RNA-binding protein, was found to be associated with tumorigenesis. However, the roles of hMex-3A in hepatocellular carcinoma (HCC) progression remained unclear. METHODS: The different expression of hMex-3A between HCC tissues and non-tumor tissues were evaluated using The Cancer Genome Atlas database. Thereafter, the hMex-3A expression was evaluated in HCC tissues using Western blotting and qRT-PCR. Immunohistochemistry was performed to investigate the association between hMex-3A level and clinicopathological features including prognosis in HCC patients. In addition, we used si-hMex-3A to knockdown hMex-3A in HCC cells to test Cell Counting Kit-8, colony formation, cell migration and invasion. RESULTS: The hMex-3A expression was significantly elevated in HCC tissues. Analysis of the clinicopathological parameters suggested that hMex-3A expression was significantly associated with pathological grade (P = 0.019) and TNM stage (P = 0.001) in HCC. Moreover, univariate and multivariate Cox-regression analyses revealed that high hMex-3A expression (HR=1.491, 95% CI: 1.107-2.007; P = 0.009) was an independent risk factor for overall survival in HCC patients. Finally, we confirmed that si-hMex-3A could significantly inhibit HCC cell proliferation, migration, and invasion in vitro. CONCLUSIONS: HMex-3A may contribute to the progression of HCC and might be used as a novel therapeutic target and prognostic marker in HCC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA