Publications by authors named "Nan Cao"

121 Publications

Survey on Visual Analysis of Event Sequence Data.

IEEE Trans Vis Comput Graph 2021 Jul 27;PP. Epub 2021 Jul 27.

Event sequence data record series of discrete events in the time order of occurrence. They are commonly observed in a variety of applications ranging from electronic health records to network logs, with the characteristics of large-scale, high-dimensional and heterogeneous. This high complexity of event sequence data makes it difficult for analysts to manually explore and find patterns, resulting in ever-increasing needs for computational and perceptual aids from visual analytics techniques to extract and communicate insights from event sequence datasets. In this paper, we review the state-of-the-art visual analytics approaches, characterize them with our proposed design space, and categorize them based on analytical tasks and applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TVCG.2021.3100413DOI Listing
July 2021

Interpretable Anomaly Detection in Event Sequences via Sequence Matching and Visual Comparison.

IEEE Trans Vis Comput Graph 2021 Jun 30;PP. Epub 2021 Jun 30.

Anomaly detection is a common analytical task that aims to identify rare cases that differ from the typical cases that make up the majority of a dataset. When analyzing event sequence data, the task of anomaly detection can be complex because the sequential and temporal nature of such data results in diverse definitions and flexible forms of anomalies. This, in turn, increases the difficulty in interpreting detected anomalies. In this paper, we propose a visual analytic approach for detecting anomalous sequences in an event sequence dataset via an unsupervised anomaly detection algorithm based on Variational AutoEncoders. We further compare the anomalous sequences with their reconstructions and with the normal sequences through a sequence matching algorithm to identify event anomalies. A visual analytics system is developed to support interactive exploration and interpretations of anomalies through novel visualization designs that facilitate the comparison between anomalous sequences and normal sequences. Finally, we quantitatively evaluate the performance of our anomaly detection algorithm, demonstrate the effectiveness of our system through case studies, and report feedback collected from study participants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TVCG.2021.3093585DOI Listing
June 2021

Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes.

Genome Biol 2021 Jun 13;22(1):180. Epub 2021 Jun 13.

Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Background: Canonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms.

Results: Here, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher mA levels than their cognate protein-coding genes, associated with de novo mA peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated mA motifs during evolution. The mA sites of pseudogenes are evolutionarily younger than neutral sites and their mA levels are increasing, supporting the idea that mA on the RNAs of pseudogenes is under positive selection. We then find that the mA RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the mA RNA modification of two processed pseudogenes, DSTNP2 and NAP1L4P1, which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genes DSTN and NAP1L4. In addition, the mA of DSTNP2 regulation of DSTN is partially dependent on the miRNA miR-362-5p.

Conclusions: Our discovery reveals a novel evolutionary role of mA RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13059-021-02402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201931PMC
June 2021

Polysaccharide of Atractylodes macrocephala Koidz regulates LPS-mediated mouse hepatitis through the TLR4-MyD88-NFκB signaling pathway.

Int Immunopharmacol 2021 Jun 8;98:107692. Epub 2021 Jun 8.

Zhongkai University of Agriculture and Engineering, Guangzhou, Guangdong 510225, China; Guangdong Province Key Laboratory of Waterfowl Healthy Breeding, Guangzhou, Guangdong 510225, China. Electronic address:

Feed corruption and poor breeding environment could cause widespread bacterial infection which could cause severe liver inflammation and lead to liver damage, even death. It has been proved that Polysaccharide of Atractylodes macrocephala Koidz (PAMK) could improve the immunity of animal, but the mechanism of its protective effect on hepatitis has been rarely reported. This study investigated the protective effect of PAMK on mouse liver through LPS-induced liver inflammatory. The results showed that LPS caused swelling of hepatocytes, disappearance of hepatic cord structure and infiltration of a large number of inflammatory cells, and LPS could up-regulated mRNA and protein expression levels of TLR4, MyD88, IKBα and NFκB, increased cytokines IL-1β, IL-4, IL-6 and TNF-α levels, enhance the levels of antioxidant enzymes CAT, GSH-PX, SOD, iNOs and MDA. PAMK pretreatment could relieved histopathological damage caused by LPS, and could activate the TLR4-MyD88-NFκB signalling pathway, reduce the levels of IL-1β, IL-6 and TNF-α, increase IL-4 levels, inhibit the levels of GSH-PX and MDA. These results indicate that PAMK could reduce inflammatory damage and oxidative stress in mice and play a protective role in the early stages of LPS invasion of the liver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2021.107692DOI Listing
June 2021

Improving NKCC1 Function Increases the Excitability of DRG Neurons Exacerbating Pain Induced After TRPV1 Activation of Primary Sensory Neurons.

Front Cell Neurosci 2021 25;15:665596. Epub 2021 May 25.

The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Physiology, Shihezi University Medical College, Shihezi, China.

Our aim was to investigate the effects of the protein expression and the function of sodium, potassium, and chloride co-transporter (NKCC1) in the dorsal root ganglion (DRG) after activation of transient receptor potential vanilloid 1 receptor (TRPV1) in capsaicin-induced acute inflammatory pain and the possible mechanism of action. Male Sprague-Dawley rats were randomly divided into control, capsaicin, and inhibitor groups. The expression and distribution of TRPV1 and NKCC1 in rat DRG were observed by immunofluorescence. Thermal radiation and acetone test were used to detect the pain threshold of heat and cold noxious stimulation in each group. The expressions of NKCC1 mRNA, NKCC1 protein, and p-NKCC1 in the DRG were detected by PCR and western blotting (WB). Patch clamp and chloride fluorescent probe were used to observe the changes of GABA activation current and intracellular chloride concentration. After intrathecal injection of protein kinase C (PKC) inhibitor (GF109203X) or MEK/extracellular signal-regulated kinase (ERK) inhibitor (U0126), the behavioral changes and the expression of NKCC1 and p-ERK protein in L DRG were observed. TRPV1 and NKCC1 were co-expressed in the DRG. Compared with the control group, the immunofluorescence intensity of NKCC1 and p-NKCC1 in the capsaicin group was significantly higher, and the expression of NKCC1 in the nuclear membrane was significantly higher than that in the control group. The expression of NKCC1 mRNA and protein of NKCC1 and p-NKCC1 in the capsaicin group were higher than those in the control group. After capsaicin injection, GF109203X inhibited the protein expression of NKCC1 and p-ERK, while U0126 inhibited the protein expression of NKCC1. In the capsaicin group, paw withdrawal thermal latency (WTL) was decreased, while cold withdrawal latency (CWL) was prolonged. Bumetanide, GF109203X, or U0126 could reverse the effect. GABA activation current significantly increased in the DRG cells of the capsaicin group, which could be reversed by bumetanide. The concentration of chloride in the DRG cells of the capsaicin group increased, but decreased after bumetanide, GF109203X, and U0126 were administered. Activation of TRPV1 by exogenous agonists can increase the expression and function of NKCC1 protein in DRG, which is mediated by activation of PKC/p-ERK signaling pathway. These results suggest that DRG NKCC1 may participate in the inflammatory pain induced by TRPV1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2021.665596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185156PMC
May 2021

Targeted RNA N -Methyladenosine Demethylation Controls Cell Fate Transition in Human Pluripotent Stem Cells.

Adv Sci (Weinh) 2021 06 18;8(11):e2003902. Epub 2021 Mar 18.

The Seventh Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, 510080, P.R. China.

Deficiency of the N -methyladenosine (m A) methyltransferase complex results in global reduction of m A abundance and defective cell development in embryonic stem cells (ESCs). However, it's unclear whether regional m A methylation affects cell fate decisions due to the inability to modulate individual m A modification in ESCs with precise temporal control. Here, a targeted RNA m A erasure (TRME) system is developed to achieve site-specific demethylation of RNAs in human ESCs (hESCs). TRME, in which a stably transfected, doxycycline-inducible dCas13a is fused to the catalytic domain of ALKBH5, can precisely and reversibly demethylate the targeted m A site of mRNA and increase mRNA stability with limited off-target effects. It is further demonstrated that temporal m A erasure on a single site of SOX2 is sufficient to control the differentiation of hESCs. This study provides a versatile toolbox to reveal the function of individual m A modification in hESCs, enabling cell fate control studies at the epitranscriptional level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202003902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188216PMC
June 2021

Polysaccharide of atractylodes macrocephala koidz activated T lymphocytes to alleviate cyclophosphamide-induced immunosuppression of geese through novel_mir2/CD28/AP-1 signal pathway.

Poult Sci 2021 Jul 15;100(7):101129. Epub 2021 Mar 15.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China. Electronic address:

Polysaccharide Of Atractylodes Macrocephala Koidz (PAMK) has been proved to have anti-cancer, antitumor, anti-inflammation function and improve the immune level of the organism. The miRNA plays a very important role in regulating the immune function by negatively regulate the expression of target genes. To explore the molecular mechanism of PAMK active the lymphocytes, thirty 61-d-old geese were randomly divided into 4 groups (C, CTX, PAMK, PAMK+CTX). The thymus morphology, the level of serum granulocyte-macrophage colony-stimulating factor (GMC-SF), IL-1β, IL-3, IL-5, the relative mRNA expression of CD25, novel_mir2, CTLA4 and CD28 signal pathway were measured. Further more, the lymphocytes was extracted from thymus to measure the relative mRNA expression of CD28 signal pathway. The results showed that PAMK could significantly maintain normal cell morphology of thymus, alleviate the decrease level of GMC-SF, IL-1β, IL-5, IL-6, TGF-β, the increase level of IL-4, IL-10, and the decrease relative mRNA expression of novel_mir2, CD25 and CD28 signal pathway in thymus and lymphocytes induced by cyclophosphamide (CTX). In conclusion, PAMK alleviated the decreased T lymphocytes activation levels induced by CTX through novel_mir2/CTLA4/CD28/AP-1 signal pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2021.101129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170423PMC
July 2021

Rapid degradation of tetracycline in aqueous solution by Fe/Cu catalysis enhanced by HO activation.

Environ Technol 2021 Jun 7:1-9. Epub 2021 Jun 7.

Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu, People's Republic of China.

Tetracycline (TC) is widely detected in the environment because of its abuse and persistence. There is an urgent need to efficiently treat TC due to its potential threat to the ecosystem and human health. In this study, microscale Fe/Cu bimetallic particles' (mFe/Cu) catalysis enhanced by HO was proposed to remove TC in an aqueous solution. Based on the pre-experiment, the effect of theoretical Cu mass loading (TML) and some key operating parameters on the TC removal efficiency were investigated thoroughly. The degradation rates of TC by mFe/Cu with different TML followed the pseudo-first-order kinetics model, and the optimal TML (0.34 g Cu/g Fe) was obtained. The optimal operating parameters of mFe/Cu dosage, concentration of HO, initial concentration of TC, stirring speed and operating temperature were 5 g/L, 50 mM, 50 ppm, 400 r/min, and 55°C, respectively. Compared with the control system, the system of mFe/Cu catalysis enhanced by HO (mFe/Cu-HO) presented excellent performance due to its synergistic effect. Also, the fresh and reacted mFe/Cu was characterized by scanning electron microscope, which showed the surface of mFe/Cu was rougher after reaction, indicating mFe/Cu participated in the degradation reaction. Besides, with the presence of inorganic anions, the degradation of TC in mFe/Cu-HO system did not change much. And mFe/Cu presented good stability and recyclability after 10 repeated tests. Therefore, mFe/Cu-HO system had a great potential for cost-effective removal of antibiotics in wastewater.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09593330.2021.1933610DOI Listing
June 2021

Clinical significance of immunohistochemistry to detect BRAF V600E mutant protein in thyroid tissues.

Medicine (Baltimore) 2021 Apr;100(16):e25566

Department of Pathology, The Second Hospital of Dalian Medical University.

Abstract: This study investigated the feasibility of using immunohistochemistry (IHC) instead of PCR to detect BRAF V600E mutant protein in papillary thyroid carcinoma (PTC), and to determine the value of using preoperative BRAF V600E mutant protein by IHC to assist in the diagnosis of thyroid nodule patients with Hashimoto's thyroiditis (HT).The expression of BRAFV600E mutant protein was measured in 23 cases of HT+PTC, 31 cases of PTC, and 28 cases of HT by IHC, followed by PCR in the same samples for validation. SPSS 19.0 software was used for statistical analysis.The sensitivity and specificity of IHC to detect BRAF V600E mutation were 100% and 42.86%, respectively. In addition, the mutation rate of BRAF V600E protein in the HT+PTC group (34.78%, 8/23) was lower than that in the PTC group (80.65%, 25/31).The application of IHC to detect BRAF V600E mutant protein has good sensitivity but not specificity to diagnose PTC. IHC can be used as a preliminary screening method to detect BRAF V600E mutation. The strongly positive (+++) staining of IHC potently indicated BRAF V600E gene mutation. For suspicious thyroid nodules combined with HT, the detection of BRAF V600E mutant protein with IHC alone is not of great significance for differentiating benign and malignant nodules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000025566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078443PMC
April 2021

Smile or Scowl? Looking at Infographic Design Through the Affective Lens.

IEEE Trans Vis Comput Graph 2021 Jun 12;27(6):2796-2807. Epub 2021 May 12.

Infographics are frequently promoted for their ability to communicate data to audiences affectively. To facilitate the creation of affect-stirring infographics, it is important to characterize and understand people's affective responses to infographics and derive practical design guidelines for designers. To address these research questions, we first conducted two crowdsourcing studies to identify 12 infographic-associated affective responses and collect user feedback explaining what triggered affective responses in infographics. Then, by coding the user feedback, we present a taxonomy of design heuristics that exemplifies the affect-related design factors in infographics. We evaluated the design heuristics with 15 designers. The results showed that our work supports assessing the affective design in infographics and facilitates the ideation and creation of affective infographics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TVCG.2021.3074582DOI Listing
June 2021

Galectin-3 participates in PASMC migration and proliferation by interacting with TGF-β1.

Life Sci 2021 Jun 11;274:119347. Epub 2021 Mar 11.

Department of Physiology, Shihezi University Medical College, Shihezi 832002, China; NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Shihezi 832002, China; The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University Medical College, Shihezi 832002, China; Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan 430070, China; Department of Physiology, Huazhong University of Science and Technology of Basic Medical Sciences, Wuhan 430070, China. Electronic address:

Pulmonary vascular remodelling is one of the most important factors for pulmonary hypertension (PH). Galectin-3 (Gal-3) is a β-galactoside-binding lectin. In the latest literature, Gal-3 has been reported to be involved in pulmonary vascular remodelling, and its underlying mechanism is unclear. Our research aims to prove the effect of Gal-3 on the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMC) induced by transforming growth factor β1 (TGF-β1) and to study its mechanism. In vivo experiment: In Sprague-Dawley (SD) rats, monocrotaline was injected intraperitoneally to establish a PH model, and the Gal-3 inhibitor (modified citrus pectin, MCP) 28 Ds was administered in the stomach. The results indicate that Gal-3 and TGF-β1 may be involved in the occurrence and development of PH, which may be related to the Smad2/3 signalling pathway. In vitro experiment: Human pulmonary artery smooth muscle cells were pretreated with the Gal-3 inhibitor (MCP) for 24 h, then TGF-β1 or Gal-3 was administered to the cells for 24 h. The results show that exogenous TGF-β1 and Gal-3 can activate the downstream Smad2/3 signalling pathway, and increase the proliferation and migration ability of HPASMC. However, the Gal-3 inhibitor (MCP) inhibited these effects. Further results display that TGF-β1 and Gal-3 could mutually regulate the protein and mRNA expression levels. In summary, the results of this study indicate that Gal-3 regulates the Smad2/3 signalling pathway through protein interaction with TGF-β1, in turn regulates the proliferation and migration of HPASMC, thereby regulating the occurrence and development of PH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119347DOI Listing
June 2021

PAMK Relieves LPS-Induced Enteritis and Improves Intestinal Flora Disorder in Goslings.

Evid Based Complement Alternat Med 2021 22;2021:9721353. Epub 2021 Feb 22.

College of Animal Science & Technology, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, China.

Polysaccharide of Koidz (PAMK) is a biologically active component of , which has the effect of maintaining the immune homeostasis of the body. Therefore, this study constructed a model of PAMK to relieve LPS-induced gosling enteritis and observed the morphological changes of the small intestine after HE staining. ELISA was used to detect serum CRP, IL-1, IL-6, and TNF- levels; immunohistochemistry was used to detect the positive rate of IgA in the small intestine; TLR4, occludin, ZO-1, cytokines, and immunoglobulin mRNA expression in the small intestine were detected by qPCR; and intestinal flora of gosling excrement was analyzed by 16S rDNA sequencing to analyze the protective effect of PAMK on goslings enteritis and the impact on intestinal flora. The results showed that PAMK relieves LPS-induced gosling enteritis by maintaining the small intestine morphology, cytokine, tight junctions, and immunoglobulin relatively stable and improving the disorder of intestinal flora.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9721353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920704PMC
February 2021

Human pluripotent stem cell-based cardiovascular disease modeling and drug discovery.

Pflugers Arch 2021 Jul 8;473(7):1087-1097. Epub 2021 Mar 8.

Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Heart diseases are prevalent worldwide and account for the highest mortality than any other illness. Although investment in drug discovery and development has increased, the amount of drug approvals has seen a progressive decline. Moreover, adverse side effects to the heart have become the most common reasons for preclinical project cessation, partly due to the lack of suitable humanized preclinical models. Human pluripotent stem cells (hPSCs) have emerged as a powerful non-animal platform to model heart disease, to screen for novel drugs, and to test drug cardiotoxicity in a high-throughput and cost-effective manner. Here, we review and discuss recent breakthroughs in the development of cardiovascular modeling and their current and future applications of hPSC-based drug discovery and testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00424-021-02542-1DOI Listing
July 2021

Core transcription regulatory circuitry orchestrates corneal epithelial homeostasis.

Nat Commun 2021 01 18;12(1):420. Epub 2021 Jan 18.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060, Guangzhou, China.

Adult stem cell identity, plasticity, and homeostasis are precisely orchestrated by lineage-restricted epigenetic and transcriptional regulatory networks. Here, by integrating super-enhancer and chromatin accessibility landscapes, we delineate core transcription regulatory circuitries (CRCs) of limbal stem/progenitor cells (LSCs) and find that RUNX1 and SMAD3 are required for maintenance of corneal epithelial identity and homeostasis. RUNX1 or SMAD3 depletion inhibits PAX6 and induces LSCs to differentiate into epidermal-like epithelial cells. RUNX1, PAX6, and SMAD3 (RPS) interact with each other and synergistically establish a CRC to govern the lineage-specific cis-regulatory atlas. Moreover, RUNX1 shapes LSC chromatin architecture via modulating H3K27ac deposition. Disturbance of RPS cooperation results in cell identity switching and dysfunction of the corneal epithelium, which is strongly linked to various human corneal diseases. Our work highlights CRC TF cooperativity for establishment of stem cell identity and lineage commitment, and provides comprehensive regulatory principles for human stratified epithelial homeostasis and pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20713-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814021PMC
January 2021

Erratum to: Regulation of IL12B Expression in Human Macrophages by TALEN-mediated Epigenome Editing.

Curr Med Sci 2020 Dec;40(6):1204

Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11596-020-2310-1DOI Listing
December 2020

Sustainable Chromium (VI) Removal from Contaminated Groundwater Using Nano-Magnetite-Modified Biochar via Rapid Microwave Synthesis.

Molecules 2020 Dec 28;26(1). Epub 2020 Dec 28.

Cranfield Water Science Institute, Cranfield University, College Road, Cranfield, Bedfordshire MK43 0AL, UK.

This study developed a nano-magnetite-modified biochar material (m-biochar) using a simple and rapid in situ synthesis method via microwave treatment, and systematically investigated the removal capability and mechanism of chromium (VI) by this m-biochar from contaminated groundwater. The m-biochar was fabricated from reed residues and magnetically modified by nano-FeO. The results from scanning electron microscopy (SEM) and X-ray diffraction (XRD) characterisations confirmed the successful doping of nano-FeO on the biochar with an improved porous structure. The synthesised m-biochar exhibited significantly higher maximum adsorption capacity of 9.92 mg/g compared with that (8.03 mg/g) of the pristine biochar. The adsorption kinetics followed the pseudo-second-order model and the intraparticle diffusion model, which indicated that the overall adsorption rate of Cr(VI) was governed by the processes of chemical adsorption, liquid film diffusion and intramolecular diffusion. The increasing of the pH from 3 to 11 significantly affected the Cr(VI) adsorption, where the capabilities decreased from 9.92 mg/g to 0.435 mg/g and 8.03 mg/g to 0.095 mg/g for the m-biochar and pristine biochar, respectively. Moreover, the adsorption mechanisms of Cr(VI) by m-biochar were evaluated and confirmed to include the pathways of electrostatic adsorption, reduction and complexation. This study highlighted an effective synthesis method to prepare a superior Cr(VI) adsorbent, which could contribute to the effective remediation of heavy metal contaminations in the groundwater.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26010103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795963PMC
December 2020

Polysaccharide of Koidz (PAMK) Alleviates Cyclophosphamide-induced Immunosuppression in Mice by Upregulating CD28/IP3R/PLCγ-1/AP-1/NFAT Signal Pathway.

Front Pharmacol 2020 8;11:529657. Epub 2020 Dec 8.

Guangdong Province Key Laboratory of Waterfowl Healthy Breeding, College of Animal Science and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, China.

The polysaccharide of Koidz (PAMK) is recognized as an immune enhancer, with anti-cancer, anti-tumour, lymphocyte-activating and lymphocytes proliferation-inducing effects. For investigating the mechanism that PAMK alleviates the decline in T cell activation induced by CTX, 24 6-week-old BALB/c female mice were randomly divided into four groups (C, PAMK, CTX, PAMK + CTX). The spleen index, splenocytes morphology and death, cytokine concentration, T cell activating factors (CD25, CD69, CD71), mRNA expression levels related to the CD28 signal pathway were detected. Furthermore, the lymphocytes of mice was isolated and cultured, and then the Th1/Th2 ratio, activating factors, mRNA levels related to the CD28 signal pathway were detected. The results showed that PAMK significantly improved the spleen index, alleviated abnormal splenocytes morphology and death, maintained the balance of Th1/Th2 cells, increased the levels of IL-2, IL-6, TNF-α, and IFN-γ, and increased the mRNA levels of CD28, PLCγ-1, IP3R, NFAT, and AP-1. In conclusion, PAMK increased cytokines levels and alleviated the decline in activation level of lymphocytes induced by CTX through CD28/IP3R/PLCγ-1/AP-1/NFAT signal pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.529657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753208PMC
December 2020

Early pregnancy affects the expression of toll-like receptor pathway in ovine thymus.

Reprod Biol 2020 Dec 4;20(4):547-554. Epub 2020 Nov 4.

College of Life Sciences and Food Engineering, Hebei University of Engineering, Handan, 056038, China. Electronic address:

Toll-like receptors (TLRs) participates in regulation of the maternal immune tolerance during pregnancy, and the thymus is critical for the adaptive immune system. This study hypothesized whether early pregnancy affected the expression of toll-like receptor pathway in the thymus of ewes. In this study, expression of TLRs, tumor necrosis factor receptor associated factor 6 (TRAF6), interleukin 1 receptor associated kinase 1 (IRAK1) and myeloid differentiation primary response gene 88 (MyD88) was detected in maternal thymus during early pregnancy in sheep. Ovine thymuses were collected on day 16 of the estrous cycle, and days 13, 16 and 25 of pregnancy, and expression of TLR members was analyzed by real-time quantitative PCR, western blot and immunohistochemistry analysis. The results revealed that there were decreases in the expression of the mRNA and proteins of TLR2, IRAK1, TRAF6 and MyD88, but increase in TLR5 mRNA and protein. Furthermore, expression of TLR3 and TLR4 proteins peaked at days 13 and 16 of gestation, and MyD88 protein was located in the epithelial reticular cells and thymic corpuscles. In summary, TLR signaling is implicated in regulation of maternal thymic immune, which may be via downregulation of TLR2, IRAK1, TRAF6 and MyD88 during early pregnancy in sheep.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.repbio.2020.10.003DOI Listing
December 2020

Regulation of IL12B Expression in Human Macrophages by TALEN-mediated Epigenome Editing.

Curr Med Sci 2020 Oct 29;40(5):900-909. Epub 2020 Oct 29.

College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Although the exact etiology of inflammatory bowel disease (IBD) remains unclear, exaggerated immune response in genetically predisposed individuals has been reported. Th1 and Th17 cells mediate IBD development. Macrophages produce IL-12 and IL-23 that share p40 subunit encoded by IL12B gene as heteromer partner to drive Th1 and Th17 differentiation. The available animal and human data strongly support the pathogenic role of IL-12/IL-23 in IBD development and suggest that blocking p40 might be the potential strategy for IBD treatment. Furthermore, aberrant alteration of some cytokines expression via epigenetic mechanisms is involved in pathogenesis of IBD. In this study, we analyzed core promoter region of IL12B gene and investigated whether IL12B expression could be regulated through targeted epigenetic modification with gene editing technology. Transcription activator-like effectors (TALEs) are widely used in the field of genome editing and can specifically target DNA sequence in the host genome. We synthesized the TALE DNA-binding domains that target the promoter of human IL12B gene and fused it with the functional catalytic domains of epigenetic enzymes. Transient expression of these engineered enzymes demonstrated that the TALE-DNMT3A targeted the selected IL12B promoter region, induced loci-specific DNA methylation, and down-regulated IL-12B expression in various human cell lines. Collectively, our data suggested that epigenetic editing of IL12B through methylating DNA on its promoter might be developed as a potential therapeutic strategy for IBD treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11596-020-2249-2DOI Listing
October 2020

Visual Causality Analysis of Event Sequence Data.

IEEE Trans Vis Comput Graph 2021 Feb 28;27(2):1343-1352. Epub 2021 Jan 28.

Causality is crucial to understanding the mechanisms behind complex systems and making decisions that lead to intended outcomes. Event sequence data is widely collected from many real-world processes, such as electronic health records, web clickstreams, and financial transactions, which transmit a great deal of information reflecting the causal relations among event types. Unfortunately, recovering causalities from observational event sequences is challenging, as the heterogeneous and high-dimensional event variables are often connected to rather complex underlying event excitation mechanisms that are hard to infer from limited observations. Many existing automated causal analysis techniques suffer from poor explainability and fail to include an adequate amount of human knowledge. In this paper, we introduce a visual analytics method for recovering causalities in event sequence data. We extend the Granger causality analysis algorithm on Hawkes processes to incorporate user feedback into causal model refinement. The visualization system includes an interactive causal analysis framework that supports bottom-up causal exploration, iterative causal verification and refinement, and causal comparison through a set of novel visualizations and interactions. We report two forms of evaluation: a quantitative evaluation of the model improvements resulting from the user-feedback mechanism, and a qualitative evaluation through case studies in different application domains to demonstrate the usefulness of the system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TVCG.2020.3030465DOI Listing
February 2021

Calliope: Automatic Visual Data Story Generation from a Spreadsheet.

IEEE Trans Vis Comput Graph 2021 Feb 28;27(2):453-463. Epub 2021 Jan 28.

Visual data stories shown in the form of narrative visualizations such as a poster or a data video, are frequently used in data-oriented storytelling to facilitate the understanding and memorization of the story content. Although useful, technique barriers, such as data analysis, visualization, and scripting, make the generation of a visual data story difficult. Existing authoring tools rely on users' skills and experiences, which are usually inefficient and still difficult. In this paper, we introduce a novel visual data story generating system, Calliope, which creates visual data stories from an input spreadsheet through an automatic process and facilities the easy revision of the generated story based on an online story editor. Particularly, Calliope incorporates a new logic-oriented Monte Carlo tree search algorithm that explores the data space given by the input spreadsheet to progressively generate story pieces (i.e., data facts) and organize them in a logical order. The importance of data facts is measured based on information theory, and each data fact is visualized in a chart and captioned by an automatically generated description. We evaluate the proposed technique through three example stories, two controlled experiments, and a series of interviews with 10 domain experts. Our evaluation shows that Calliope is beneficial to efficient visual data story generation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TVCG.2020.3030403DOI Listing
February 2021

[Up-regulation of connexin 43 (Cx43) by angiotensin II promotes the proliferation and migration of human pulmonary artery smooth muscle cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 Jul;36(7):616-621

Ministry-of-Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Physiology, School of Medicine, Shihezi University, Shihezi 832000; Department of Physiology, Faculty of Basic Medical Sciences, Huazhong University of Science and Technology, Wuhan 430030, China. *Corresponding author, E-mail:

Objective To explore the role of Cx43 in the proliferation and migration of human pulmonary arterial smooth muscle cells (HPASMCs) induced by angiotensin II (Ang II). Methods HPASMCs were cultured in vitro and randomly divided into four groups: control group, Ang II group, Ang II combined with DMSO group, and Ang II combined with candesartan group, and cells were collected in logarithmic growth phase. Cell viability was detected by CCK-8 assay; the migration ability of HPASMCs were measured by wound-healing and Transwell assay. The protein levels of Cx43, osteopontin (OPN), proliferating cell nuclear antigen (PCNA), SMAD2 and SMAD3 in HPASMCs were detected by Western blot analysis. Results Compared with the control group, the expression of OPN and PCNA proteins significantly went up in Ang II group, and the cell proliferation and migration ability increased. The cell proliferation and migration ability of the Ang II combined with candesartan group were significantly lower than that in the Ang II group. Compared with the control group, the Cx43 protein and its phosphorylation level increased significantly in the Ang II group, and the protein expression of SMAD2 and SMAD3 increased, while the expression of each protein in the Ang II combined with candesartan group was significantly lower than those in the Ang II group. Conclusion Ang II up-regulates the expression of Cx43 protein to promote the proliferation and migration of HPASMCs, which may be related to the activation of SMAD2/3 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2020

Perspective on human pluripotent stem cell-derived cardiomyocytes in heart disease modeling and repair.

Stem Cells Transl Med 2020 10 29;9(10):1121-1128. Epub 2020 Jul 29.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences (CAS), Shanghai, People's Republic of China.

Heart diseases (HDs) are the leading cause of morbidity and mortality worldwide. Despite remarkable clinical progress made, current therapies cannot restore the lost myocardium, and the correlation of genotype to phenotype of many HDs is poorly modeled. In the past two decades, with the rapid developments of human pluripotent stem cell (hPSC) biology and technology that allow the efficient preparation of cardiomyocytes from individual patients, tremendous efforts have been made for using hPSC-derived cardiomyocytes in preclinical and clinical cardiac therapy as well as in dissection of HD mechanisms to develop new methods for disease prediction and treatment. However, their applications have been hampered by several obstacles. Here, we discuss recent advances, remaining challenges, and the potential solutions to advance this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sctm.19-0340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519762PMC
October 2020

Changes in expression of interferon-stimulated genes and ubiquitin activating enzyme E1-like in ovine thymus during early pregnancy.

Anim Reprod 2020 Jun 29;17(2):e20190134. Epub 2020 Jun 29.

Department of Animal Science, College of Life Sciences and Food Engineering, Hebei University of Engineering, Handan, China.

As the main signal for the maternal recognition in ruminants, interferon-tau (IFNT) stimulates expression of interferon-stimulated genes (ISGs) in uterus and many extrauterine tissues. However, it is unclear that early pregnancy induces expression of signal transducer and activator of transcription 1 (STAT1), myxovirusresistance 1 (Mx1), interferon-gamma-inducible protein 10 (IP-10) and ubiquitin activating enzyme E1-like protein (UBE1L) in maternal thymus. In this study, ovine thymuses were sampled on day 16 of the estrous cycle and on days 13, 16 and 25 of gestation, and the expression of STAT1, Mx1, IP-10 and UBE1L was detected by real-time quantitative PCR, Western blot and immunohistochemistry. The results revealed that the expression of STAT1 and IP-10 reached peaks on day 16 of pregnancy, and expression of Mx1 was enhanced on day 25 of pregnancy, and STAT1 protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. However, expression of UBE1L was declined during early pregnancy. In conclusion, early pregnancy influences expression of STAT1, Mx1, IP-10 and UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1984-3143-AR2019-0134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375869PMC
June 2020

[Monocrotaline pyrrole induces A549 cells and activates TGF-β1/SMAD2/SMAD3 pathway to promote proliferation and migration of human pulmonary artery smooth muscle cells].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2020 Jun;36(6):527-534

Ministry-of-Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Physiology, Shihezi University, Shihezi 832000; Department of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. *Corresponding author, E-mail:

Objective To explore the effects of A549 cells on the proliferation and migration of human pulmonary arterial smooth muscle cells (HPASMCs) and its mechanism. Methods A549 cells and HPASMCs were cultured in vitro. The A549 cells were randomly divided into four groups: control group, dimethylformamide (DMF) solvent group, monocrotaline pyrrole (MCTP) group, MCTP combined with SB431542 group. The cells were assigned into four groups: HPASMC group, A549 and HPASMC co-culture group, MCTP-stimulated A549 and HPASMC co-culture group, MCTP and SB431542-stimulated A549 and HPASMC co-culture group, and IL-6-stimulated HPASMC group. A549 cell viability was detected by CCK-8 assay. The level of IL-6 in the A549 cell culture supernatant was tested by ELISA. The mRNA levels of SMAD2 and SMAD3 in the A549 cells were detected by real-time PCR. The protein levels of TGF-β1, SMAD2, SMAD3 and p-SMAD2, p-SMAD3 in the A549 cells were detected by Western blot analysis. The protein levels of TGF-β1, SMAD2, SMAD3 and p-SMAD2, p-SMAD3 in the A549 cells were examined by Western blot analysis. The protein levels of osteopontin (OPN) and proliferating nuclear antigen (PCNA) in the HPASMCs were determined by Western blot analysis. The migration ability of HPASMCs was measured by wound healing and Transwell assay. Results In the A549 cells, compared with the control group, the cell proliferation ability decreased, the production of IL-6 increased, the mRNA levels of SMAD2 and SMAD3, and the expression of TGF-β1, SMAD2, SMAD3, p-SMAD2, p-SMAD3 proteins significantly increased in the MCTP group. Compared with the MCTP group, the cell proliferation ability increased, the production of IL-6 decreased, the mRNA levels of SMAD 2 and SMAD3, and the expression of TGF-β1, SMAD2, SMAD3, p-SMAD2, p-SMAD3 proteins significantly decreased in the MCTP and SB431542-stimulated group. In the co-culture system, compared with the HPASMC group, the expression of PCNA and OPN proteins and migration ability did not change significantly in the A549 and HPASMC co-cultured group. The expression of PCNA and OPN proteins significantly increased in the MCTP-stimulated A549 and HPASMC co-culture group, and the cell migration ability increased. Compared with the MCTP-stimulated A549 and HPASMC co-culture group, the expression of PCNA and OPN proteins significantly decreased in MCTP and SB431542-stimulated A549 and HPASMC co-culture group, and the cell migration ability decreased. Compared with the HPASMC group, the migration ability of HPASMCs increased and the expression of PCNA and OPN proteins increased in the IL-6 control group. Conclusion Activation of the TGF-β1/SMAD2/SMAD3 signaling pathway in A549 cells induced by MCTP increases IL-6 secretion, thus promoting the proliferation and migration of HPASMCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2020

Downregulation of LAPTM4B Contributes to the Impairment of the Autophagic Flux via Unopposed Activation of mTORC1 Signaling During Myocardial Ischemia/Reperfusion Injury.

Circ Res 2020 09 22;127(7):e148-e165. Epub 2020 Jul 22.

CAS Key Laboratory of Tissue Microenvironment and Tumor, Laboratory of Molecular Cardiology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences (CAS), CAS (S.G., J.T., Q.L., S.L., Y.Z., J.L., W.B., P.S., X.L., H.-T.Y.).

Rationale: Impaired autophagic flux contributes to ischemia/reperfusion (I/R)-induced cardiomyocyte death, but the underlying molecular mechanisms remain largely unexplored.

Objective: To determine the role of LAPTM4B (lysosomal-associated transmembrane protein 4B) in the regulation of autophagic flux and myocardial I/R injury.

Methods And Results: LAPTM4B was expressed in murine hearts but downregulated in hearts with I/R (30 minutes/2 hours) injury and neonatal rat cardiomyocytes with hypoxia/reoxygenation (6 hours/2 hours) injury. During myocardial reperfusion, LAPTM4B-knockout (LAPTM4B) mice had a significantly increased infarct size and lactate dehydrogenase release, whereas adenovirus-mediated LAPTM4B-overexpression was cardioprotective. Concomitantly, LAPTM4B mice showed higher accumulation of the autophagy markers LC3-II (microtubule-associated protein 1A/1B-light chain 3), but not P62, in the I/R heart, whereas they did not alter chloroquine-induced further increases of LC3-II and P62 in both sham and I/R hearts. Conversely, LAPTM4B-overexpression had opposite effects. The hypoxia/reoxygenation-reduced viability of neonatal rat cardiomyocytes, ratio of autolysosomes/autophagosomes, and function of lysosomes were further decreased by LAPTM4B-knockdown but reversed by LAPTM4B-overexpression. Moreover, the LAPTM4B-overexpression-mediated benefits were abolished by knockdown of lysosome-associated membrane protein-2 (an autophagosome-lysosome fusion protein) in vivo and by the autophagy inhibitor bafilomycin A1 in vivo. In contrast, rapamycin (Rapa) successfully restored the impaired autophagic flux in LAPTM4B mice and the subsequent myocardial I/R injury. Mechanistically, LAPTM4B regulated the activity of mTORC1 (mammalian target of rapamycin complex 1) via interacting with mTOR through its EC3 (extracelluar) domain. Thus, mTORC1 was overactivated in LAPTM4B mice, leading to the repression of TFEB (transcription factor EB), a master regulator of lysosomal and autophagic genes, during myocardial I/R. The mTORC1 inhibition or TFEB-overexpression rescued the LAPTM4B-induced impairment in autophagic flux and I/R injury, whereas TFEB-knockdown abolished the LAPTM4B-overexpression-mediated recovery of autophagic flux and cardioprotection.

Conclusions: The downregulation of LAPTM4B contributes to myocardial I/R-induced impairment of autophagic flux via modulation of the mTORC1/TFEB pathway. Graphic Abstract: A graphic abstract is available for this article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCRESAHA.119.316388DOI Listing
September 2020

Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers.

Nucleic Acids Res 2020 07;48(13):7182-7196

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China.

Hippo-YAP signaling pathway functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. We found that knockout (KO) of Mst1 and Mst2, two key components of the Hippo signaling in mouse embryonic stem cells (ESCs), resulted in a disruption of differentiation into mesendoderm lineage. To further uncover the underlying regulatory mechanisms, we performed a series of ChIP-seq experiments with antibodies against YAP, ESC master transcription factors and some characterized histone modification markers as well as RNA-seq assays using wild type and Mst KO samples at ES and day 4 embryoid body stage respectively. We demonstrate that YAP is preferentially co-localized with super-enhancer (SE) markers such as Nanog, Sox2, Oct4 and H3K27ac in ESCs. The hyper-activation of nuclear YAP in Mst KO ESCs facilitates the binding of Nanog, Sox2 and Oct4 as well as H3K27ac modification at the loci where YAP binds. Moreover, Mst depletion results in novel SE formation and enhanced liquid-liquid phase-separated Med1 condensates on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Our study reveals a novel mechanism on how Hippo-YAP signaling pathway dictates ESC lineage differentiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gkaa482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367178PMC
July 2020

Development and Validation of a Deep Learning Model for Non-Small Cell Lung Cancer Survival.

JAMA Netw Open 2020 06 1;3(6):e205842. Epub 2020 Jun 1.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Importance: There is a lack of studies exploring the performance of a deep learning survival neural network in non-small cell lung cancer (NSCLC).

Objectives: To compare the performances of DeepSurv, a deep learning survival neural network with a tumor, node, and metastasis staging system in the prediction of survival and test the reliability of individual treatment recommendations provided by the deep learning survival neural network.

Design, Setting, And Participants: In this population-based cohort study, a deep learning-based algorithm was developed and validated using consecutive cases of newly diagnosed stages I to IV NSCLC between January 2010 and December 2015 in a Surveillance, Epidemiology, and End Results database. A total of 127 features, including patient characteristics, tumor stage, and treatment strategies, were assessed for analysis. The algorithm was externally validated on an independent test cohort, comprising 1182 patients with stage I to III NSCLC diagnosed between January 2009 and December 2013 in Shanghai Pulmonary Hospital. Analysis began January 2018 and ended June 2019.

Main Outcomes And Measures: The deep learning survival neural network model was compared with the tumor, node, and metastasis staging system for lung cancer-specific survival. The C statistic was used to assess the performance of models. A user-friendly interface was provided to facilitate the survival predictions and treatment recommendations of the deep learning survival neural network model.

Results: Of 17 322 patients with NSCLC included in the study, 13 361 (77.1%) were white and the median (interquartile range) age was 68 (61-74) years. The majority of tumors were stage I disease (10 273 [59.3%]) and adenocarcinoma (11 985 [69.2%]). The median (interquartile range) follow-up time was 24 (10-43) months. There were 3119 patients who had lung cancer-related death during the follow-up period. The deep learning survival neural network model showed more promising results in the prediction of lung cancer-specific survival than the tumor, node, and metastasis stage on the test data set (C statistic = 0.739 vs 0.706). The population who received the recommended treatments had superior survival rates than those who received treatments not recommended (hazard ratio, 2.99; 95% CI, 2.49-3.59; P < .001), which was verified by propensity score-matched groups. The deep learning survival neural network model visualization was realized by a user-friendly graphic interface.

Conclusions And Relevance: The deep learning survival neural network model shows potential benefits in prognostic evaluation and treatment recommendation with respect to lung cancer-specific survival. This novel analytical approach may provide reliable individual survival information and treatment recommendations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.5842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272121PMC
June 2020

Application of curved ablation in liver cancer with special morphology or location: Report of two cases.

World J Clin Cases 2020 May;8(9):1713-1720

Department of Ultrasound, Zhejiang Hospital, Hangzhou 310013, Zhejiang Province, China.

Background: Liver cancer is one of the most common malignant tumors with a high incidence and mortality. Hepatitis-liver cirrhosis-liver cancer is known as the trilogy of liver cancer. At present, due to significant development of imaging interventions, they occupy an irreplaceable position in the field of liver cancer treatment, especially ultrasound-guided ablation. Because patients with liver cancer often present with liver cirrhosis, which leads to morphological deformation of the liver, it is difficult to perform a linear ablation of liver cancer in the areas near the phrenic top and within large blood vessels, among others. The present study reports on two cases of liver cancer that have been subjected to curvilinear ablation. After 1 mo, magnetic resonance imaging showed complete ablation, demonstrating that ultrasound-guided curved ablation is feasible and effective in the treatment of liver cancer.

Case Summary: Two patients were treated at the Liver Disease Department of the Xixi Hospital Affiliated to Zhejiang University of Chinese Medicine in 2019. Because the first liver cancer patient's tumor was located close to the diaphragm, it was difficult to complete a straight needle ablation procedure in one session. In order to achieve accurate and minimally invasive treatment of this tumor, a curved needle ablation procedure was designed. The second patient presented with a hepatic cyst in front of the tumor. In order not to damage the hepatic cyst, a looper needle ablation technique was used. The procedure was successfully completed in both cases.

Conclusion: Curved ablation is a new technique that can be used to treat tumors situated in a variety of locations, providing new ideas for interventional techniques. Its operation difficulty is higher and further animal experiments are necessary to improve the operation procedure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v8.i9.1713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211519PMC
May 2020

SETDB1 promotes the progression of colorectal cancer via epigenetically silencing p21 expression.

Cell Death Dis 2020 05 11;11(5):351. Epub 2020 May 11.

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.

SETDB1, a histone H3K9 methyltransferase, has been reported to be upregulated in a variety of tumors and promotes cancer development. However, the exact pathogenesis of SETDB1 in human colorectal cancer (CRC) is hitherto unknown. Here, we showed that SETDB1 expression was highly amplified in CRC. Functionally, SETDB1 downregulation in SW480 and HCT116 cells reduced cell proliferation, migration, invasion, and increased CRC cells apoptosis. In contrast, SETDB1 overexpression promoted CRC cells proliferation, migration, and invasion. High expression of SETDB1 was associated with a more aggressive phenotype in vitro. Flow cytometry showed that cell cycle was arrested in G1 phase after SETDB1 silencing. Furthermore, depletion of SETDB1 in vivo suppressed CRC cells proliferation. Mechanistically, p21 was identified as the target of SETDB1. After transfected with siSETDB1, expression of p21 was distinctly increased. In contrast, expression of p21 was significantly decreased after overexpression SETDB1. We also showed that SETDB1 could be involved in the regulation of epithelial-mesenchymal transition (EMT) in HCT116 cells. Moreover, we confirmed that SETDB1 could regulate the activity of p21 promoter by dual-luciferase repoter assay, and proved that SETDB1 could bind to the promoter of p21 and regulate its H3K9me3 enrichment level by ChIP-PCR experiment. Finally, we verified that silencing of SETDB1 inhibited CRC tumorigenesis in vivo. In conclusion, our results indicate that SETDB1 is a major driver of CRC development and might provide a new therapeutic target for the clinical treatment of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2561-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214465PMC
May 2020
-->