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1.
Biomolecules ; 9(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31684108

RESUMO

Human high-mobility group A2 (HMGA2) encodes for a non-histone chromatin protein which influences a variety of biological processes, including the cell cycle process, apoptosis, the DNA damage repair process, and epithelial-mesenchymal transition. The accumulated evidence suggests that high expression of HMGA2 is related to tumor progression, poor prognosis, and a poor response to therapy. Thus, HMGA2 is an important molecular target for many types of malignancies. Our recent studies revealed the positive connections between heat shock protein 90 (Hsp90) and HMGA2 and that the Hsp90 inhibitor has therapeutic potential to inhibit HMGA2-triggered tumorigenesis. However, 43% of patients suffered visual disturbances in a phase I trial of the second-generation Hsp90 inhibitor, NVP-AUY922. To identify a specific inhibitor to target HMGA2, the Gene Expression Omnibus (GEO) database and the Library of Integrated Network-based Cellular Signatures (LINCS) L1000platform were both analyzed. We identified the approved small-molecule antifungal agent ciclopirox (CPX) as a novel potential inhibitor of HMGA2. In addition, CPX induces cytotoxicity of colorectal cancer (CRC) cells by induction of cell cycle arrest and apoptosis in vitro and in vivo through direct interaction with the AT-hook motif (a small DNA-binding protein motif) of HMGA2. In conclusion, this study is the first to report that CPX is a novel potential inhibitor of HMGA2 using a drug-repurposing approach, which can provide a potential therapeutic intervention in CRC patients.

2.
Pancreas ; 48(10): 1303-1306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31688593

RESUMO

OBJECTIVES: Small cell lung carcinoma (SCLC) is a highly malignant tumor characterized by early metastasis even at the time of diagnosis. Although pancreatic metastasis occurring in SCLC is a common observation in the literatures, there is currently very limited experience with the metastasis-induced acute pancreatitis in SCLC patients. METHODS: Here we retrospectively analyzed patients with metastasis-induced acute pancreatitis and SCLC in West China Hospital between 2009 and 2017. The patients were diagnosed as having SCLC by bronchoscopic biopsy or computed tomography-guided percutaneous biopsy. Metastasis-induced pancreatitis was established by clinical symptoms, radiologic surveillance, serum amylase, and lipase level. The series included 14 patients, 4 women and 10 men, with a mean age of 54 years (range, 29-76 years). The patients underwent chemotherapy plus palliative treatment (n = 8) or palliative care alone (n = 6). RESULTS: Compared with patients receiving palliative treatment alone, a trend toward improved survival was observed in patients who underwent chemotherapy. CONCLUSION: Our personal experience indicated that chemotherapy might provide a survival benefit in SCLC patients with metastasis-induced pancreatitis, especially those with good performance status.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31675212

RESUMO

High-throughput screening and fast identification of single bacterial cells are crucial for clinical diagnosis, bioengineering, and fermentation engineering. Although single-cell technologies have been developed extensively in recent years, the single-cell technologies for bacteria still need further exploration. In this study, we demonstrate an identification and screening technology for single bacterial cells based on a large-scale nanobowl array, which is well-ordered and size-adjustable for use with different kinds of bacteria. When the culture medium with monodispersed bacteria was placed on the nanobowl array, it successfully enabled loading of single bacterium into a single nanobowl. Because of the limitative size and depth of the nanobowls, mixture of different bacteria species could be screened according to their sizes. In addition, with the help of a low electrical current, the bacteria can be further screened according to their intrinsic surface charges. If combined with micromanipulation technology, high-throughput single bacterial selection can be achieved in future.

4.
BMC Gastroenterol ; 19(1): 177, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699035

RESUMO

BACKGROUND: Choledocholithiasis is an endemic condition in the world. Although rare, foreign body migration with biliary complications needs to be considered in the differential diagnosis for patients presenting with typical symptoms even many years after cholecystectomy, EPCP, war-wound, foreign body ingestion or any other particular history before. It is of great clinical value as the present review may offer some help when dealing with choledocholithiasis caused by foreign bodies. CASE PRESENTATION: We reported a case of choledocholithiasis caused by fishbone from choledochoduodenal anastomosis regurgitation. Moreover, we showed up all the instances of choledocholithiasis caused by foreign bodies published until June 2018 and wrote the world's first literature review of foreign bodies in the bile duct of 144 cases. The findings from this case suggest that the migration of fishbone can cause various consequences, one of these, as we reported here, is as a core of gallstone and a cause of choledocholithiasis. CONCLUSION: The literature review declared the choledocholithiasis caused by foreign bodies prefer the wrinkly and mainly comes from three parts: postoperative complications, foreign body ingestion, and post-war complications such as bullet injury and shrapnel wound. The Jonckheere-Terpstra test indicated the ERCP was currently the treatment of choice. It is a very singular case of choledocholithiasis caused by fishbone, and the present review is the first one concerning choledocholithiasis caused by foreign bodies all over the world.

6.
Plant Cell Physiol ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31693150

RESUMO

Although control of xylem ion loading is essential to confer salinity stress tolerance, specific details behind this process remain elusive. In this work, we compared kinetics of xylem Na+ and K+ loading between two halophytes (Atriplex lentiformis and quinoa) and two glycophyte (pea and beans) species, to understand the mechanistic basis of the above process. Halophyte plants had high initial amounts of Na+ in the leaf, even when grown in the absence of the salt stress. This was matched by 7-fold xylem sap Na+ concentration compared with glycophyte plants. Upon salinity exposure, the xylem sap Na+ concentration increased rapidly but transiently in halophytes, while in glycophytes this increase was much delayed. Electrophysiological experiments using the MIFE technique showed that glycophyte plants tend to re-absorb Na+ back into the stele, thus reducing xylem Na+ load at the early stages of salinity exposure. The halophyte plants, however, were capable to release Na+ even in the presence of high Na+ concentrations in the xylem. The presence of H2O2 (mimicking NaCl-stress induced ROS accumulation in the root) caused a massive Na+ and Ca2+ uptake into the root stele, while triggering a substantial K+ efflux from the cytosol into apoplast in glycophyte but not halophytes species. The peak in H2O2 production was achieved faster in halophytes (30 min vs 4 h) and was attributed to the increased transcript levels of RbohE. Pharmacological data suggested that non-selective cation channels are unlikely play a major role in ROS-mediated xylem Na+ loading.

7.
Environ Pollut ; : 113581, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31753641

RESUMO

Soil application of Zn fertilizer is an effective approach to improve yield and Zn accumulation in wheat grain. However, it remains unclear whether repeated Zn application can result in high accumulation of heavy metals (HMs) in soils and grains and thus represents a potential risk for human consumption. This study aimed to evaluate the health risk assessment of HMs in a wheat production system which had continuously received 8 years of Zn application at varying rates (0, 2.3, 5.7, 11.4, 22.7, 34.1 kg Zn ha-1). The results showed that Zn application significantly increased the soil total Zn concentration without affecting concentrations of As, Pb, Cd, Cu and Cr. Across Zn rates, Zn application increased grain concentrations of Zn, Pb and Cd by 75%, 51% and 14%, respectively, and reduced grain As concentration by 14%. The human health risk assessment revealed that the threshold hazard quotients for the individual HM were below 1, independent of Zn rates. The hazard index (HI) values at Zn rates of 11.4, 22.7 and 34.1 kg Zn ha-1 were significantly greater than that at null Zn treatment. Furthermore, exposures to As, Cu and Zn accounted for 97% of HI at all Zn rates. Analysis of the threshold cancer risk with Pb and As showed that ingestion of wheat grain even from highest Zn application rate wouldn't bring the lifetime carcinogenic risk. In contrast, long-term Zn application significantly reduced the carcinogenic risk of As by 9.7-26.5%. In conclusion, repeated soil applications of Zn at optimal rate (5.7 kg Zn ha-1) didn't cause health risk for Zn, Cu, Cd, Pb, Cr, and As, while improving productivity and grain Zn concentration of wheat to meet human recruitment. Our study highlights the importance of appropriate Zn fertilizer management in improving grain quality while reducing HMs risks from human consumption.

8.
J Sex Med ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31735614

RESUMO

INTRODUCTION: Premature ejaculation (PE) is a highly prevalent male sexual dysfunction. Previous studies have found abnormal activity in the sympathetic nervous system and penile sensory pathway of PE. Few studies have investigated the neural mechanisms underlying PE. AIM: The aim of this study was to examine whether the altered cortico-subcortical network topological properties of the brain white matter structural network could be used to differentiate patients with PE from healthy control (HC) subjects. METHODS: Diffusion tensor images data were collected from 32 patients with PE and 35 HC participants. Then, brain white matter structural networks were reconstructed from image acquisition. MAIN OUTCOME MEASURE: Furthermore, nodal measures were calculated and hub regions were identified using the graph-theoretical methods. RESULTS: For cortical brain regions, increased strength, global efficiency, and decreased shortest path length were found in the right superior frontal gyrus (medial), and superior frontal gyrus (medial orbital) were found in patients with PE. In addition, patients with PE also showed decreased strength in the right rolandic operculum and decreased shortest path length, and increased global efficiency in the right inferior frontal gyrus (triangular part). For subcortical brain structures, patients with PE were associated with decreased shortest path length and increased global efficiency in the left insula and right caudate nucleus. Finally, the results showed that 9 PE-specific hub regions were identified in patients compared with HCs, including 7 cortical regions and 2 subcortical regions. CLINICAL IMPLICATIONS: Our results provide new understanding about the pathology of PE and enhances the understanding of PE pathology. STRENGTH & LIMITATIONS: Our results offer biological markers for understanding the physiopathology of PE. However, our study is a cross-sectional design, longitudinal design studies need to explore the causal relationships between aberrant topological characteristics and PE. CONCLUSION: Our results provide new insights into the neural mechanism of PE involving cortico-subcortical network changes, which could serve as a potential biomarker to differentiate individuals with PE from HCs. Chen J, Yang J, Huang X, et al. Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study. J Sex Med 2019;XX:XXX-XXX.

9.
Twin Res Hum Genet ; : 1-4, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31708009

RESUMO

The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.

10.
Future Oncol ; 15(34): 3917-3934, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31729887

RESUMO

Aim: To elucidate the integrative combinational gene regulatory network landscape of hepatocellular carcinoma (HCC) molecular carcinogenesis from diverse background. Materials & methods: Modified gene regulatory network analysis was used to prioritize differentially regulated genes and links. Integrative comparisons using bioinformatics methods were applied to identify potential critical molecules and pathways in HCC with different backgrounds. Results: E2F1 with its surrounding regulatory links were identified to play different key roles in the HCC risk factor dysregulation mechanisms. Hsa-mir-19a was identified as showed different effects in the three HCC differential regulation networks, and showed vital regulatory role in HBV-related HCC. Conclusion: We describe in detail the regulatory networks involved in HCC with different backgrounds. E2F1 may serve as a universal target for HCC treatment.

11.
J Viral Hepat ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31667945

RESUMO

We examined whether the hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after nucleos(t)ide (NA) treatment can predict the long-time prognoses of chronic hepatitis B patients. Patients with chronic hepatitis B (98) who were treatment-naïve and had begun a 7-year NA therapy regimen were enrolled in this study. Biochemical indicators and serological markers of HBV infection were performed during therapy. HBV pgRNA was quantified by real-time quantitative PCR with specific primers. During treatment, HBV DNA undetectable rates increased. The aminotransferase (ALT) normalization (ALT < 50 IU/L) and HBeAg-negative rates also increased. After 48 weeks' NA treatment, 48.28% (28/58) of HBV DNA undetectable patients still had HBV pgRNA-positive. After 7 years of treatment, more HBV pgRNA-negative patients (n = 35) achieved HBeAg clearance than the patients who were HBV pgRNA-positive (n = 63) (19/23 vs 19/56, P < .00). HBV pgRNA-positive patients also had an increased risk of failing to achieve HBeAg clearance (OR = 9.25, 95% CI: 2.75-31.08). The median time to HBeAg clearance in the HBV pgRNA-positive patients was longer than that of the HBV pgRNA-negative patients (152 weeks vs 72 weeks). The HBV pgRNA-positive patients also required more time to achieve HBV DNA undetectable (124 weeks, 95% CI: 103.33-144.67 vs 48 weeks, 95% CI: 34.80-61.20). The HBV pgRNA status after NA treatment can predict the long-term prognoses of patients with chronic HBV. Patients who remain HBV pgRNA-positive after 48 weeks of NA treatment have an increased risk of not achieving HBeAg clearance, need more time to achieve HBeAg clearance and undetectable HBV DNA load.

12.
Cells ; 8(12)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766744

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3'-untranslated region (3'-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial-mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC.

13.
Sci Rep ; 9(1): 16580, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719561

RESUMO

Although researchers have determined that attaining high grain yields of winter wheat depends on the spike number and the shoot biomass, a quantitative understanding of how phosphorus (P) nutrition affects spike formation, leaf expansion and photosynthesis is still lacking. A 3-year field experiment with wheat with six P application rates (0, 25, 50, 100, 200, and 400 kg P ha-1) was conducted to investigate this issue. Stem development and mortality, photosynthetic parameters, dry matter accumulation, and P concentration in whole shoots and in single tillers were studied at key growth stages for this purpose. The results indicated that spike number contributed the most to grain yield of all the yield components in a high-yielding (>8 t/ha) winter wheat system. The main stem (MS) contributed 79% to the spike number and tiller 1 (T1) contributed 21%. The 2.7 g kg-1 tiller P concentration associated with 15 mg kg-1 soil Olsen-P at anthesis stage led to the maximal rate of productive T1s (64%). The critical shoot P concentration that resulted in an adequate product of Pn and LAI was identified as 2.1 g kg-1. The thresholds of shoot P concentration that led to the maximum productive ability of T1 and optimal canopy photosynthetic capacity at anthesis were very similar. In conclusion, the thresholds of soil available P and shoot P concentration in whole plants and in single organs (individual tillers) were established for optimal spike formation, canopy photosynthetic capacity, and dry matter accumulation. These thresholds could be useful in achieving high grain yields while avoiding excessive P fertilization.

14.
Int J Artif Organs ; : 391398819882697, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31665956

RESUMO

OBJECTIVE: This study aims to evaluate the effectiveness of individualized hemodialysis for unconventional hypotension in diabetic nephropathy patients. METHODS: A total of 60 patients were selected and randomly divided into study group and control group. The control group used the standard dialysis model, while the study group used the individualized hemodialysis scheme, in which the dialysis was performed using an individualized dialysis machine temperature control, pattern of natrium, and pattern of step ultrafiltration in combination with dialysate-containing glucose. RESULTS: The total occurrence rate of hypotension, dry weight standard-reaching rate, and blood quality during and after dialysis in the study group were superior to those in the control group (P < 0.05). Furthermore, the symptom scores in the study group (dizziness score, chest distress score, sweating score, muscle spasm score, gastrointestinal symptom score, and temporary mind change score) were lower than those in the control group (P < 0.05). The serum sodium, potassium, and chloride concentration in these two groups after dialysis was not statistically different (P > 0.05). CONCLUSION: The combined application of low temperature, pattern of natrium, pattern of step ultrafiltration, and dialysate-containing glucose individualization is safe and effective for preventing and controlling the occurrence of intradialytic hypotension (IDH), improve symptoms, and improve the dry weight standard-reaching rate.

15.
Stem Cells ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670434

RESUMO

Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases such as Stargardt's disease, age-related macular degeneration, and retinitis pigmentosa. The final impact of all retinal dystrophies is the loss of photoreceptors; hence, there is a pressing need for research into replacement. Seminal work has shown that a simple three-dimensional culture system enables differentiation of human pluripotent stem cells to retinal organoids containing large numbers of photoreceptors developing alongside retinal neurons and Müller glia cells in a laminated structure that resembles the native retina. Despite these promising developments, current protocols show different efficiencies across pluripotent stem cells and result in retinal organoids with a mixture of photoreceptor cells at varying maturation states, along with nonphotoreceptor cell types. In this study, we investigated the impact of stage-specific addition of retinoic acid (RA), 9-cis-retinal, 11-cis-retinal, levodopa (l-DOPA), triiodothyronine (T3), and γ-secretase inhibitor ((2S)-N-[(3,5-Difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine1,1-dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 120 of differentiation enhanced the generation of rod and S-cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 of differentiation led to enhanced generation of L/M-cones at the expense of rods. l-DOPA when added together with RA during days 90 to 120 of differentiation also promoted the emergence of S-cones at the expense of rod photoreceptors. Collectively, these data represent an advance in our ability to direct generation of rod and cone photoreceptors in vitro. Stem Cells 2019.

16.
Interdiscip Sci ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741225

RESUMO

The argonaute protein (Ago) exists in almost all organisms. In eukaryotes, it functions as a regulatory system for gene expression. In prokaryotes, it is a type of defense system against foreign invasive genomes. The Ago system has been engineered for gene silencing and genome editing and plays an important role in biological studies. With an increasing number of genomes and proteomes of various microbes becoming available, computational tools for identifying and annotating argonaute proteins are urgently needed. We introduce AGONOTES (Argonaute Notes). It is a web service especially designed for identifying and annotating Ago. AGONOTES uses the BLASTP similarity search algorithm to categorize all submitted proteins into three groups: prokaryotic argonaute protein (pAgo), eukaryotic argonaute protein (eAgo), and non-argonaute protein (non-Ago). Argonaute proteins can then be aligned to the corresponding standard set of Ago sequences using the multiple sequence alignment program MUSCLE. All functional domains of Ago can further be curated from the alignment results and visualized easily through Bio::Graphic modules in the BioPerl bundle. Compared with existing tools such as CD-Search and available databases such as UniProt and AGONOTES showed a much better performance on domain annotations, which is fundamental in studying the new Ago. AGONOTES can be freely accessed at http://i.uestc.edu.cn/agonotes/. AGONOTES is a friendly tool for annotating Ago domains from a proteome or a series of protein sequences.

17.
J Comput Biol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31750732

RESUMO

This study aimed to assess mRNA and lncRNA expression differences between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Cancer tissues were obtained from three LUSC and three LUAD patients, followed by RNA-seq. Differentially expressed mRNAs (DE-mRNAs) and lncRNAs (DE-lncRNAs) were identified between LUSC and LUAD, after which functional enrichment analysis and protein-protein interaction (PPI) network construction was performed on DEGs. Coexpression analysis of lncRNA-gene and prediction of DEG-related miRNAs as well as function enrichment analysis, and construction of competing endogenous RNAs (ceRNA) regulatory network were then conducted. Moreover, survival analysis on differentially expressed RNAs was performed based on data downloaded from The Cancer Genome Atlas (TCGA) database. In this study, 518 DEGs and 117 DE-lncRNAs were identified between LUSC and LUAD. The DEGs were mainly associated with cell adhesion, PI3K-Akt signaling pathway, and focal adhesion. PPI network analysis indicated several genes with highest connectivity, such as CCND1. DE-lncRNAs that coexpressed with DEGs were also associated with tight junction and DE-lncRNAs that had more corepressed relationships with DEGs included GSEC, NKX2-1-AS1, LINC01415, and LINC00839. Moreover, the genes and lncRNAs with higher connectivity in the ceRNA network included NEAT1, SLC5A3, LINC00839, ETV1, CMTM4, and SNX30. Several genes were significantly related to the survival of patients with LUSC and LUAD, including ETV1, RTKN2, SNX30, PAK2, and CCND1. Genes and lncRNAs associated with cell junction have specific patterns in two major histological subtypes of NSCLC. GSEC, NKX2-1-AS1, NEAT1, CCND1, and ETV1 may be potential novel biomarkers for personalized treatment strategies of NSCLC.

18.
Int J Cancer ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31721169

RESUMO

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan-Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from the TCGA. Finally, we used GEPIA to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies. This article is protected by copyright. All rights reserved.

19.
Tissue Cell ; 61: 61-66, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31759408

RESUMO

Neural stem cells (NSCs) generated neurons and glial cells. Thus, it is a preferable candidate to the cell replacement-based therapy against neural disorders. The signaling pathways that regulate differentiation of NSCs are widely studied. In the current study, we used in vitro culture system to elucidate the role of signal transducer and activator of transcription 1 (STAT1) in NSCs' differentiation. Downregulation of STAT1 inhibited the proliferation of NSCs. Meanwhile, we also found STAT1 regulation could control the differentiation of NSCs. More neurons and glia cells were generated from NSCs with STAT1 silencing. This process was mediated by the JNK/STAT1 signaling. STAT1 inhibitor promoted differentiation of NSCs. After transplantation, we observed more neurons generated from NSCs with shRNA-STAT1 treatment. Collectively, this work showed an efficient way to regulate neuronal differentiation of NSCs through regulating the STAT1 expression. This is likely to provide source and theoretical support to cell replacement based theory.

20.
Sci Rep ; 9(1): 17470, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767951

RESUMO

Circulating tumor cells (CTCs) shed from solid tumors can serve as a minimally invasive liquid biopsy for monitoring disease progression. Because CTCs are rare and heterogeneous, their biological properties need to be investigated at the single cell level, which requires efficient ways to isolate and analyze live single CTCs. Current methods for CTC isolation and identification are either performed on fixed and stained cells or need multiple procedures to isolate pure live CTCs. Here, we used the AccuCyte-RareCyte system to develop a Protocol for Integrated Capture and Retrieval of Ultra-pure single live CTCs using Negative and positive selection (PIC&RUN). The positive selection module of PIC&RUN identifies CTCs based on detection of cancer surface markers and exclusion of immune markers. Combined with a two-step cell picking protocol to retrieve ultrapure single CTCs, the positive selection module is compatible for downstream single cell transcriptomic analysis. The negative selection module of PIC&RUN identifies CTCs based on a live cell dye and the absence of immune markers, allowing retrieval of viable CTCs that are suitable for ex vivo culture. This new assay combines the CTC capture and retrieval in one integrated platform, providing a valuable tool for downstream live CTC analyses.

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