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1.
Int J Cancer ; 146(2): 400-412, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31271662

RESUMO

Histone demethylases are promising therapeutic targets as they play fundamental roles for survival of Mixed lineage leukemia rearranged acute leukemia (MLLr AL). Here we focused on the catalytic Jumonji domain of histone H3 lysine 9 (H3K9) demethylase JMJD1C to screen for potential small molecular modulators from 149,519 natural products and 33,765 Chinese medicine components via virtual screening. JMJD1C Jumonji domain inhibitor 4 (JDI-4) and JDI-12 that share a common structural backbone were detected within the top 15 compounds. Surface plasmon resonance analysis showed that JDI-4 and JDI-12 bind to JMJD1C and its family homolog KDM3B with modest affinity. In vitro demethylation assays showed that JDI-4 can reverse the H3K9 demethylation conferred by KDM3B. In vivo demethylation assays indicated that JDI-4 and JDI-12 could induce the global increase of H3K9 methylation. Cell proliferation and colony formation assays documented that JDI-4 and JDI-12 kill MLLr AL and other malignant hematopoietic cells, but not leukemia cells resistant to JMJD1C depletion or cord blood cells. Furthermore, JDI-16, among multiple compounds structurally akin to JDI-4/JDI-12, exhibits superior killing activities against malignant hematopoietic cells compared to JDI-4/JDI-12. Mechanistically, JDI-16 not only induces apoptosis but also differentiation of MLLr AL cells. RNA sequencing and quantitative PCR showed that JDI-16 induced gene expression associated with cell metabolism; targeted metabolomics revealed that JDI-16 downregulates lactic acids, NADP+ and other metabolites. Moreover, JDI-16 collaborates with all-trans retinoic acid to repress MLLr AML cells. In summary, we identified bona fide JMJD1C inhibitors that induce preferential death of MLLr AL cells.

2.
Arch Insect Biochem Physiol ; 103(1): e21636, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31612557

RESUMO

As a member of the low-density lipoprotein receptor (LDLR) superfamily, vitellogenin (Vg) receptor (VgR) is responsible for the uptake of Vg into developing oocytes and is a potential target for pest control. Here, a full-length VgR complementary DNA (named as CsVgR) was isolated and characterized in the rice stem borer, Chilo suppressalis. The composite CsVgR gene contained an open reading frame of 5,484 bp encoding a protein of 1,827 amino acid residues. Structural analysis revealed that CsVgR contained two ligand-binding domains (LBDs) with four Class A (LDLRA ) repeats in LBD1 and seven in LBD2, which was structurally different from most non-Lepidopteran insect VgRs having five repeats in LBD1 and eight in LBD2. The developmental expression analysis showed that CsVgR messenger RNA expression was first detectable in 3-day-old pupae, sharply increased in newly emerged female adults, and reached a peak in 2-day-old female adults. Consistent with most other insects VgRs, CsVgR was exclusively expressed in the ovary. Notably, injection of dsCsVgR into late pupae resulted in fewer follicles in the ovarioles as well as reduced fecundity, suggesting a critical role of CsVgR in female reproduction. These results may contribute to the development of RNA interference-mediated disruption of reproduction as a control strategy of C. suppressalis.

3.
Arch Oral Biol ; 109: 104584, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630006

RESUMO

OBJECTIVES: To investigate whether rutin could protect human periodontal ligament stem cells (hPDLSCs) from TNF-α induced damage to osteogenic differentiation in inflammatory environment and detect the underlying mechanism. MATERIALS AND METHODS: hPDLSCs were identified by flow cytometery. TNF-α was used to stimulate hPDLSCs to establish an inflammation model in vitro. Alkaline phosphatase (ALP) staining, ALP activity test, and Alizarin Red staining were used to detect the changes of osteogenic differentiation ability. The mRNA and protein levels of osteogenic genes were evaluated by RT-PCR and Western Blot. The expression of mTOR was also detected by Western Blot. RESULTS: hPDLSCs were positive to MSCs specific surface markers. The inflammatory environment in vitro could be established by stimulating hPDLSCs with TNF-α (20 ng/mL). TNF-α (20 ng/mL) could decrease the ALP activity and mineralization ability of hPDLSCs and down-regulate the expression of osteogenic genes in inflammatory environment. Moreover, rutin could affect TNF-α (20 ng/mL) induced damage to osteogenic differentiation of hPDLSCs in a dose-dependent manner, 10 µmol/L rutin could significantly reverse the damage caused by TNF-α. In addition, rutin inhibited TNF-α-activated mTOR signal transduction by inhibiting the phosphorylation of mTOR, similar to the effects of rapamycin(a specific mTOR inhibitor). CONCLUSIONS: Rutin could protect hPDLSCs from TNF-α induced damage to osteogenic differentiation in inflammatory environment, and rutin is expected to become a new candidate drug for the treatment of bone defect of periodontitis.

4.
J Hazard Mater ; 382: 121096, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31491666

RESUMO

Blue TiO2 nanotube arrays (Blue-TNTs) were fabricated via an electrochemical reduction method with formic acid as the electrolyte. The optimum reduction conditions were obtained as bias potential of -1.3 V, reduction time of 5 min and formic acid of 3 M. Blue-TNTs were remarkably corroded compared with the intact TNTs. Similar crystal structures of the two catalysts were observed using X-ray diffraction, while red-shift was observed for Blue-TNTs using Raman spectra. X-ray photoelectron spectroscopy indicated of the presence of Ti3+ in Blue-TNTs that resulted from the reduction of Ti4+ and reduced the resistance of the catalyst. Blue-TNTs exhibited much stronger light-absorption than intact TNTs over the entire ultraviolet-visible region, especially in the visible region. The catalyst was used toward the photoelectrochemical oxidation of 2,4-dichlorophenoxyacetic acid (2,4-D) for the first time where the influencing factors were studied. Photoelectrocatalysis with Blue-TNTs presented a 2,4-D degradation rate constant (0.0295 min-1) more than twice the sum of that of electrocatalysis (0.0055 min-1) and photocatalysis (0.0089 min-1). Blue-TNTs fabricated in formic acid showed a better photoelectrocatalytic performance for 2,4-D removal compared with that prepared in ethylene glycol, Na2SO4 and NaNO3 solution. Blue-TNTs is considered to be a promising photoelectric anode for contaminant degradation.

5.
J Proteomics ; 210: 103527, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31610263

RESUMO

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen causing severe economic loss. Previous studies have revealed that some proteins in silkworm digestive juice show antiviral activity. In this study, antiviral activity examination of different resistant strains showed that the digestive juice of the resistant strain (A35) had higher inhibition to virus than the susceptible strain (P50). Subsequently, the label-free quantitative proteomics was used to study the midgut digestive juice response to BmNPV infection in P50 and A35 strains. A total of 98 proteins were identified, of which 80 were differentially expressed proteins (DEPs) with 54 enzymes and 26 nonenzymatic proteins by comparing the proteomes of infected and non-infected P50 and A35 silkworms. These DEPs are mainly involved in metabolism, proteolysis, neuroactive ligand receptor interaction, starch and sucrose metabolism and glutathione metabolism. After removing the genetic background and individual immune stress response proteins, 9 DEPs were identified potentially involved in resistance to BmNPV. Further studies showed that a serine protease, an alkaline phosphatase and serine protease inhibitor 2 isoform X1 were differentially expressed in A35 compared to P50 or post BmNPV infection. Taken together, these results provide insights into the potential mechanisms for silkworm digestive juice to provide resistance to BmNPV infection. Signifcance: Bombyx mori nucleopolyhedrovirus (BmNPV) is highly pathogenic, which has a great impact on the sericulture. BmNPV entered the midgut lumen and exposed to digestive juices after oral infection. Previous studies have revealed that some proteins in silkworm digestive juice show antiviral activity, however, current information on the digestive juice proteome of high resistant silkworm strain after BmNPV challenge compared to susceptible strain is incomprehensive. Here, we combined label-free quantification method, bioinformatics, RT-qPCR and western blot analysis and found that BmNPV infection causes some protein changes in the silkworm midgut digestive juice. The DEPs were identified in the digestive juices of different resistant strains following BmNPV infection, and screened out some proteins potentially related to resistance to BmNPV. Three important differentially expression proteins were validated by independent approaches. These findings uncover the potential role of silkworm digestive juice in providing resistance to BmNPV and supplemented the profile of the proteome of the digestive juices in B. mori.

6.
Sci Total Environ ; 698: 134174, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499346

RESUMO

Subsurface wastewater infiltration systems (SWISs) have drawn much attention due to the lower operating costs, lower energy demands and absence of secondary pollutants requiring further treatment. The process of denitrification involves reduction of nitrate to nitrous oxide (N2O) and dinitrogen gas (N2). Though removal of nitrate is advantageous from a water quality perspective, N2O may contribute to adverse environmental effects. This study evaluated N2O emission at high C loading regimes. The results revealed that as the C load increased, N2O emission increased first and then decreased, indicating that carbon source was a limiting factor for the release of N2O from the denitrification process. Denitrification was the dominant process for the release of N2O at any of the given C loads. When the influent carbon load was in the range of 220-460 mg/L, the contribution of denitrification to N2O emissions came to 69.77-83.11% (feeding period) and 67.07-79.53% (rest period), respectively.

7.
J Nanosci Nanotechnol ; 20(4): 2628-2632, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492287

RESUMO

As a new topological insulator material, the ß-phase silver telluride (Ag2Te) nanowire is a narrow bandgap semiconductor, which is attractive for its excellent properties. In this study, Ag2Te nanowires were synthesized by one-step hydrothermalmethod. The nanowires showed good electrical properties with maximum drain-source voltage of 1.5 V, and the output current was up to 20 µA. The gate voltage has a significant effect on output current for the device. The Ag2Te nanowires will have more extensive and in-depth applications in the fields of optoelectronics and thermoelectricity.

8.
J Invest Surg ; : 1-7, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31795782

RESUMO

Background: This study aimed to investigate the effect of double-lumen irrigation-suction tube (DLIST) in the management of surgical site infections (SSIs) after enterocutaneous fistula (ECF) excisions. Method: From January 2016 to December 2017 medical records of patients with ECF excisions were reviewed. Patients with primary superficial SSI were divided into group a (treated with DLIST) and b (treated with delayed primary closures). Patients with primary deep SSI were divided into group A (treated with DLIST) and B (treated with vacuum-assisted closure [VAC]). The effect of the DLIST was evaluated. Results: There were 32 in group a and 27 in group b. The therapeutic time and cost in group a were lower (13.13 ± 2.37 d vs. 24.89 ± 7.44 d; p < .001; $1456 ± 302 vs.$2784 ± 583; p < .001). There were 21 in group A and 23 in group B. While the therapeutic time of group A was longer, the cost was lower ($1717 ± 404 vs. $2636 ± 592; p < .001). Conclusions: Placing DLIST is an effective and cheap method to treat superficial SSI after ECF excisions. The cost of DLIST in treatment of deep SSI is lower, while the effect of VAC is better.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31784083

RESUMO

Interleukin-17 (IL-17) and interferon-γ (IFN-γ), two inflammatory cytokines, are present in cancerous liver tissues. IL-17 was recently identified as an oncogenic factor in hepatocellular carcinoma (HCC), but its underlying mechanisms are largely obscure. Here, we aimed to investigate the interaction between IL-17 and IFN-γ and its influence on HCC cell apoptosis and growth in vitro and in vivo. We found that the expression of IL-17, but not IFN-γ, was obviously increased in HCC tissues. Higher IL-17 expression in tumor tissues correlated with shorter survival times. IFN-γ apparently increased apoptosis of HCC cells. IL-17 alone had no effect on apoptosis of HCC cells but reversed apoptosis induced by IFN-γ. IFN-γ mildly promoted the expression of protein inhibitor of activated signal transducer and activators of transcription 1 (PIAS1) and the activation of NF-κB, and these effects were greatly enhanced when combined with IL-17. PIAS1 silencing not only further amplified apoptosis induced by IFN-γ alone but also abolished the inhibitory effects of IL-17 on IFN-γ-induced apoptosis in HCC cells. An NF-κB inhibitor obviously decreased the upregulated expression of PIAS1 induced by IFN-γ plus IL-17 and IFN-γ alone. IFN-γ treatment retarded the tumor growth of HCC cells in an in vivo xenograft tumor model, which could be largely inhibited by combined treatment with IL-17. In conclusion, IL-17 obviously inhibits the antitumor effects of IFN-γ in hepatoma cells and, in turn, accelerates HCC development through upregulating the expression of the negative feedback regulator PIAS1 of the JAK/STAT1 pathway via enhancing activation of NF-κB.

10.
Shanghai Kou Qiang Yi Xue ; 28(4): 356-361, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792473

RESUMO

PURPOSE: To explore the effect of rutin on osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment. METHODS: Periodontal ligament stem cells (PDLSCs) were obtained by limited dilution method in vitro. PDLSCs were identified by flow cytometery. Lipopolysaccharide(LPS) was used to stimulate human periodontal ligament stem cells to establish an inflammation model in vitro. The experiment was divided into 4 groups: in group 1, only α-MEM was used to culture PDLSCs; in group 2, α-MEM medium containing LPS was used to culture PDLSCs, in group 3, rutin was added to α-MEM medium containing LPS to PDLSCs; and in group 4, α-MEM medium containing rutin was used to culture PDLSCs. Cell counting kit-8 was used to detect cell proliferation activity. Alkaline phosphatase(ALP) staining, ALP activity test, alizarin red staining, RT-PCR, and Western blot were used to detect the changes of osteogenic differentiation ability. The data were analyzed by SPSS 17.0 software package. RESULTS: The results of CCK-8 and ALP activity analysis showed that rutin at 10 µmol/L could significantly promote the proliferation and differentiation of periodontal stem cells under inflammatory state. ALP staining and alizarin red staining proved that (10 µmol/L) rutin could improve osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment. RT-PCR and Western blot results showed that rutin could enhance the expression of osteogenic genes and proteins such as COL1, ALP, and RUNX2 under inflammatory state. CONCLUSIONS: Rutin can promote osteogenic differentiation of periodontal ligament stem cells under inflammatory microenvironment.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31792806

RESUMO

Reperfusion arrhythmias (RA) are an important cause of sudden cardiac death and is closely associated with gap junction protein in the heart, connexin 43 (Cx43). This study is aimed at elucidating the molecular association between microRNA-206 (miR-206) and Cx43 in ischemia-reperfusion arrhythmia using experimental animal model. Our results showed that miR-206 inhibitor alleviated ischemia-reperfusion-induced arrhythmias, indicated by the lower extent of changes in heart rate (HR), PR interval, rate pressure product (RPP), and mean arterial pressure (MAP). miR-206 inhibitor also downregulated the serum creatine kinase isoenzyme (CKMB) and cardiac troponin I (cTnI) levels in mice under myocardial ischemia-reperfusion (IR) process. The knockdown of Cx43 inversed the protective effects of miR-206 inhibitor on cardiac arrhythmias. These results supported that inhibition of miR-206 ameliorates ischemia-reperfusion arrhythmia by targeting Cx43, and this miR-206/Cx43 axis could serve as a potential target for the management of ischemic-perfusion arrhythmia.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 714-719, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762243

RESUMO

OBJECTIVE: To select and identify the bacterium which highly produces protease and ß-D-glucosidase from 72 strains of Shuidouchi from Sichuan, and to provide evidence for further research on its nutritional value and fermentation strain exploiting. METHODS: Casein degradation test and pNPG chemical test were applied respectively to detect the capacity to produce protease and ß-D-glucosidase of each strain. Characteristics of morphology, biochemistry, 16S rRNA and MALDI-TOF-MS were used to identify the fermentation strain, which genetic stability, curves of growth and enzyme producing were also obtained. RESULTS: The strain with the highest enzyme activity of ß-D-glucosidase (0.084 U/L) among the top 10 strains for producing protease was selected as the fermentation strain and was identified as Bacillus subtilis, which curves of growth and enzyme producing conformed as well. The result of genetic stability showed that capacity of enzyme producing was stable until the 10th generation. CONCLUSIONS: The fermentation strain which highly produced protease and ß-D-glucosidase was selected from 72 strains of shuidouchi from Sichuan and was identified as Bacillus subtilis.


Assuntos
Bacillus subtilis/enzimologia , Alimentos Fermentados/microbiologia , Glucosidases/biossíntese , Peptídeo Hidrolases/biossíntese , Alimentos de Soja/microbiologia , China , Fermentação , RNA Ribossômico 16S
13.
Nano Lett ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31769992

RESUMO

Despite many cationic nanomaterials that have been developed for efficient adsorption of anionic pollutants, tailoring a stable shape with denser cations on the surface for advanced removal capability remains challenging. Here, a new strategy is presented for fabricating two-dimensional (2D) cationic laminas and their curvature based on cross-linking of 2D supramolecular networks from hydrogen-bonded trimesic amide derivatives. Owing to the distribution of most cations on the surface, two cationic nanostructures from cross-linking of supramolecular networks show fast sorption kinetics for anionic pollutants. Notably, the removal capacity of the capsule-like curvature adsorbent is more than twice that of lamina  adsorbent for sufficient space around cationic sites in hollow aperture. Moreover, the capsule-like adsorbent is triggered to open and spontaneously release the adsorbed pollutants upon the addition of halogen anions, which can be recovered by subsequent dialysis. Strategy of a capsule-like pocket with tunable opening-closing will provide a new insight for storage and adsorption.

14.
Neurology ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712368

RESUMO

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethno-racial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethno-racial differences that warrant attention in the development of prevention strategies.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31735331

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Protein tyrosine phosphatase 1B (PTP1B) is a member of protein tyrosine phosphatases (PTPs) family. In our previous work, PTP1B was found to be overexpressed in ESCC tissues and made contributions to the the cell migration and invasion as well as lung metastasis of ESCC. In this study, we explored the underlying molecular mechanisms. PTP1B enhanced cell migration and invasion by promoting epidermal growth factor receptor (EGFR) expression in ESCC, which was relied on phosphatase activity of PTP1B. Using GST-pulldown combined with LC/MS/MS, we found that nonmuscle myosin IIA (MYH9) was a novel substrate of PTP1B in ESCC cells. PTP1B dephosphorylated MYH9 at Y1408, by which PTP1B up-regulated EGFR expression and enhanced cell migration and invasion in ESCC. In conclusion, our study first reported that PTP1B was the positive regulator of EGFR by dephosphorylating MYH9 at Y1408 to promote cell migration and invasion, which revealed the regulatory mechanism of PTP1B-MYH9-EGFR axis in ESCC.

16.
Res Vet Sci ; 127: 42-46, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677415

RESUMO

The ORF3 protein of porcine epidemic diarrhea virus (PEDV) is found to function as an ion channel which influences virus virulence and production. Taking consideration of the importance of PEDV orf3 gene, we have performed comprehensive analysis to investigate its synonymous codon usage patterns. In this study, the results of base composition analysis showed A/T rich and G/C poor in PEDV orf3 genes, and the most abundant base was nucleotide T. The relative synonymous codon usage value in each codon revealed that codon usage bias existed. The mean ENC value of each gene was 48.75, indicating a low codon usage bias, as well as a relatively instable change in PEDV orf3 genes. The general correlation analysis between base composition and codon usage bias indicated that mutational bias has an impact on the PEDV codon usage bias. Neutral analysis suggested that natural selection pressure takes a more important influence than mutational bias in shaping codon usage bias. Moreover, other factors including hydrophobicity and aromaticity have been also found to influence the codon usage variation among the PEDV orf3 genes. This study not only represents the most systematic analysis of codon usage patterns in PEDV orf3 genes, but also provides a basic shaping mechanism of the codon usage bias.

17.
Aging (Albany NY) ; 11(21): 9719-9737, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711043

RESUMO

Tanshinone IIA (TanIIA)-an active constituent of Salvia miltiorrhiza, a traditional Chinese medicinal plant-is known to have blood circulation promotion and anti-tumor properties. Tan IIA can induce tumor cell death and inhibit tumor growth. However, the functions and underling molecular mechanisms of Tan IIA action on human liver cancer cells remain poorly understand. In this study, we found that Tanshinone IIA mediates SMAD7-YAP interaction to induce liver cancer cell apoptosis and inhibit cell growth and migration by inactivating the transforming growth factor beta (TGF-ß) signaling pathway. Our findings showed that the Tan IIA-SMAD7-YAP regulatory network might be an effective strategy for liver cancer treatment.

18.
Waste Manag ; 102: 190-197, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678805

RESUMO

In the process of landfilling, leachates resulting from the waste landfill are likely to cause secondary environmental pollution, and installation of a basal liner is essential under a landfill site to block and reduce permeation of leachate flowing into the subsurface environment. The research aims to develop a salt-resistant bentonite and a novel base liner material for offshore waste disposal. The liner materials consist of core materials and coating materials in which mixtures of bentonite, sepiolite, and guar gum were used to overcome the shortcomings in bentonite to realise a high water-resistance and a permeability coefficient of below 1.0 × 10-7 cm/s under saline water conditions. The optimal mixing ratio of bentonite, sepiolite, and guar gum was confirmed as 76:19:5 by conducting drying shrinkage cracking tests, free swelling tests, and hydraulic conductivity tests. The hydraulic conductivities of spherical particles, as measured in a rigid-wall permeameter and a flexible-wall permeameter, were less than 1.0 × 10-7 cm/s under saline water conditions. The compressive properties of spherical particles were evaluated through triaxial compression testing. The engineering characteristics of the liner material were studied in the present research, but the long-term biodegradation characteristics of polymer additives were also important, yet remained unclear. The long-term biostability of the additives, and its effect on basal liner performance should be evaluated in future research.

19.
Oncol Rep ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31746400

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a common type of esophageal cancer and is prevalent worldwide. Understanding the mechanisms underlying its formation and the search for more effective therapeutic strategies are critical due to the occurrence of chemotherapeutic drug resistance. The aim of the present study was to determine the functional relevance and therapeutic potential of carbohydrate sulfotransferase 15 (CHST15) in ESCC. CHST15 levels were measured in different ESCC cell lines and evaluated in ESCC tissues using tissue chip immunohistochemistry. Cell growth and apoptosis assays, 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assays, and clonogenic assays were conducted using TE­1 cells and lenti­shCHST15 virus constructs were used to investigate the function of CHST15 in cell proliferation and apoptosis. mRNA microarray analysis was performed to determine the underlying mechanism of CHST15 regulation in TE­1 cell proliferation and apoptosis. The results showed that knockdown of CHST15 inhibited TE­1 cell growth and proliferation, but induced cell apoptosis. CHST15 was more frequently detected in ESCC tissue compared with that in normal esophageal tissue. Microarray data analysis indicated that the inhibition of cell proliferation and activation of cell apoptosis in CHST15­knockdown cells may be caused by altered CHST15/ILKAP/CCND1 and CHST15/RABL6/PMAIP1 signaling axes, respectively.

20.
Mediators Inflamm ; 2019: 7859460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780871

RESUMO

Reg (regenerating gene) family proteins are known to be overexpressed in gastrointestinal (GI) tissues under conditions of inflammation. However, the pathophysiological significance of Reg family protein overexpression and its regulation is still unclear. In the present study, we investigated the profile of Reg family gene expression in a colitis model and focused on the regulation of Reg IIIß and IIIγ, which are overexpressed in inflamed colonic mucosa. C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks. Gene expression of the Reg family and cytokines (IL-6, IL-17, and IL-22) was evaluated by real-time RT-PCR, and Reg IIIß/γ expression was examined by immunohistochemistry. The effects of cytokines on STAT3 phosphorylation and HIP/PAP (type III REG) expression in Caco2 and HCT116 cells were examined by Western blot analysis. Among Reg family genes, Reg IIIß and IIIγ were alternatively overexpressed in the colonic tissues of mice with DSS-induced colitis. The expression of STAT3-associated cytokines (IL-6, IL-17, and IL-22) was also significantly increased in those tissues, being significantly correlated with that of Reg IIIß/γ. STAT3 phosphorylation and HIP/PAP expression were significantly enhanced in Caco2 cells upon stimulation with IL-6, IL-17, and IL-22. In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.

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