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1.
Methods Mol Biol ; 2170: 143-154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32797457

RESUMO

MicroRNAs (miRNAs) play important roles in development in plants, and some miRNAs show developmentally regulated organ- and tissue-specific expression patterns. Therefore, in situ detection of mature miRNAs is important for understanding the functions for both miRNAs and their targets. The construction of promoter-reporter fusions and examination of their in planta expression has been widely used and the results obtained thus far are rather informative; however, in some cases, the length of promoter that contains entire regulatory elements is difficult to determine. In addition, traditional in situ hybridization with the antisense RNA fragment as the probe usually fails to detect miRNAs, because the mature miRNAs are too short (~21-nucleotides) to exhibit stable hybridization signals. In recent years, the Locked nucleic acid (LNA) modified DNA probe has been successfully used in animals and plants to detect small RNAs. Here, we describe a modified protocol using LNA-modified DNA probes to detect mature miRNAs in plant tissues, including the design of LNA probes and detailed steps for the in situ hybridization experiment, using Arabidopsis miR165 as an example.

2.
Food Chem ; : 128570, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33199122

RESUMO

Novel SERS substrates is urgently in demand for rapid and sensitive analysis of toxic agrochemicals from food. In this work, a monodispersed tungsten disulfide quantum dots modified silver nanosphere (Ag@WS2QD) was prepared and used as SERS substrate. Ag@WS2QD generated uniform and stable SERS signals within 2 min, displaying great promise in "mixing and reading" detection. Compared to unmodified colloidal silver nanoparticles, 4 times higher analytical enhancement factor was found in Ag@WS2QD. Density functional theory calculation verified the enhanced charge transfer within the coupling systems of molecule-Ag@WS2QD. Besides, the unique surface properties are beneficial for the enrichment of specific molecule. Both the chemical extraction and enhanced charge transfer contributes to rapid and sensitive SERS detection of Ag@WS2QD. A "mixing and reading" SERS method for thiram from honey and four kinds of juice was developed from Ag@WS2QD, showing great promise for rapid and direct SERS detection for toxic agrochemicals and further applications.

3.
PLoS One ; 15(11): e0236203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33175875

RESUMO

BACKGROUND/AIM: To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). MATERIALS AND METHODS: Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. RESULTS: Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. CONCLUSION: By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.

4.
Biomed Res Int ; 2020: 8854245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204722

RESUMO

Cell division-related proteins are essential for the normal development and differentiation of cells and may be related to the occurrence of cancer and the drug resistance mechanism of cancer cells. The mitotic kinesin-like protein 1 (MKLP1) is a kinesin protein that has been involved in the assembly of the midzone/midbody during mitosis and cytokinesis. In this study, we found that the tail domain of MKLP1 exhibited an autoinhibitory effect on its motor activity. Overexpression of the tail domain in HEK293 cells blocked cytokinesis and caused bi-/multinucleation. It is possible that protein binding to the MKLP1 tail relieves this autoinhibition and induces the motility of MKLP1. We used the GST pull-down assay followed by the LC-MS/MS analysis and identified 54 MKLP1 tail domain-specific binding proteins. Further, we confirmed the MS result by coimmunoprecipitation and FRET that a serine/threonine kinase, p21-activated kinase 2 (PAK2), binding to MKLP1. Endogenous PAK2 expression was found to be identical to that of MKLP1 in HEK293 cells during cytokinesis. Finally, functional studies indicated that when PAK2 expression was downregulated by siRNA, MKLP1 underwent a change in its localization away from the midbody, and cell cytokinesis was subsequently impeded. This study presents a novel regulatory mechanism that PAK2 promotes the activation of MKLP1 and contributes to complete cell cytokinesis.

5.
Oncol Rep ; 44(6): 2793-2794, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125118

RESUMO

Subsequently to the publication of the article, the authors have realized that some errors were contained therein that went uncorrected before the paper was sent to press. First, Fig. 4 contained a pair of data panels that had been misplaced: The LY294002, PC­3 data panel in Fig. 4A showed the same data as the RWPE­1, control panel in Fig. 4B, and the LY294002, RWPE­1 data panel showed the same data as the matrine, control panel in Fig. 4B. These errors arose inadvertently during the process of re­organizing the layout of the figure; a corrected version of Fig. 4, showing the correct data panels for the LY294002, PC­3 and LY294002, RWPE­1 experiments in Fig. 4A and B respectively, is shown on the next page. Also note that the data shown in Fig. 4C and E have been re­calculated on the basis of the correction of the data in this Figure, and the revised histograms are also shown in these Figure parts. In view of these corrections, in the "Matrine induces cell apoptosis by increasing Bim and Bax and decreasing Bcl­2 protein levels in prostate cancer cell lines" subsection of the Results section towards the bottom of p. 2822, in the penultimate sentence, the text "...LY294002 resulted in 25.88% cell apoptosis in the PC­3 cells and 18.88% in the RWPE1 cells, compared to 3.11 and 6.89%, respectively, with LY294002 treatment only (Fig. 4A­D)." should be corrected to: "...LY294002 resulted in 25.88% cell apoptosis in the PC­3 cells and 18.88% in the RWPE1 cells, compared to 10.94% and 6.89%, respectively, with LY294002 treatment only (Fig. 4A­D)." (the changed datum is shown in bold). Note that the corrected data shown in Fig. 4, and the revision made to the Results section, do not affect the overall conclusions reported in the paper. The authors thank the Editor of Oncology Reports for allowing them the opportunity to present this Corrigendum, and apologize and to the readership for any inconvenience caused. [the original article was published in Oncology Reports 37: 2819-2828, 2017; DOI: 10.3892/or.2017.5510].

6.
Chem Commun (Camb) ; 56(90): 14051-14054, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33103676

RESUMO

A dual-functional Pt(iv) prodrug, Pt-furoxan, can release cytotoxic cisplatin and signaling molecule NO upon cellular internalization. NO modulates the cellular response towards cisplatin, leading to a synergistic anti-proliferation effect and a promising anti-metastasis effect both in vitro and in vivo.

8.
BMC Cardiovasc Disord ; 20(1): 444, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045999

RESUMO

BACKGROUND: One-stop occlusion, which is defined as the combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure, in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF. METHODS: Inpatients with AF and ASD/PFO were recruited between August 2014 and April 2019. Preoperatively, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were conducted to identify the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 45-60 days, followed with regular evaluation of TTE and TEE. RESULTS: Forty-nine patients (age, 65.6 ± 9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They were treated with LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the ASD occluders were 14.2 ± 7.7 and 25.4 ± 8.5 mm, respectively. The mean PFO size was 3.5 ± 0.4 mm. The mean maximal LAA orifice width and depth were 20.5 ± 3.4 and 28.3 ± 3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1 ± 2.9 mm). Postoperatively, all patients took anticoagulants orally for 45-60 days, and their mean postoperative follow-up duration was 29.0 ± 12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO occluders. At 45-60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients who took warfarin and novel oral anticoagulants, respectively, have developed occluder thrombosis. After adjusted anticoagulant therapy, TEE showed that the thrombus disappeared at 6 months after operation. CONCLUSION: One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.

9.
Org Lett ; 22(21): 8219-8223, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33034458

RESUMO

An In(OTf)3-catalyzed intermolecular [3 + 2] annulation for the synthesis of 2,3-dihydro-1H-benzo[e]indoles and 2,3-dihydrobenzofurans from readily available substrates has been achieved. This approach takes advantage of oxetane and para-quinone methide as important functional units in the key intermediate. ß-Naphthylamines and phenols have been demonstrated as excellent reaction partners.

10.
Int J Toxicol ; 39(6): 530-541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33063577

RESUMO

INTRODUCTION: Corrected QT (QTc) interval is an essential proarrhythmic risk biomarker, but recent data have identified limitations to its use. The J to T-peak (JTp) interval is an alternative biomarker for evaluating drug-induced proarrhythmic risk. The aim of this study was to evaluate pharmacological effects using spatial magnitude leads and DII electrocardiogram (ECG) leads and common ECG confounders (ie, stress and body temperature changes) on covariate adjusted QT (QTca), covariate adjusted JTp (JTpca), and covariate adjusted T-peak to T-end (Tpeca) intervals. METHODS: Beagle dogs were exposed to body hyper- (42 °C) or hypothermic (33 °C) conditions or were administered epinephrine to assess confounding effects on heart rate corrected QTca, JTpca, and Tpeca intervals. Dofetilide (0.1, 0.3, 1.0 mg/kg), ranolazine (100, 140, 200 mg/kg), and verapamil (7, 15, 30, 43, 62.5 mg/kg) were administered to evaluate pharmacological effects. RESULTS: Covariate adjusted QT (slope -12.57 ms/°C) and JTpca (-14.79 ms/°C) were negatively correlated with body temperature but Tpeca was minimally affected. Epinephrine was associated with QTca and JTpca shortening, which could be related to undercorrection in the presence of tachycardia, while minimal effects were observed for Tpeca. There were no significant ECG change following ranolazine administration. Verapamil decreased QTca and JTpca intervals and increased Tpeca, whereas dofetilide increased QTca and JTpca intervals but had inconsistent effects on Tpeca. CONCLUSION: Results highlight potential confounders on QTc interval, but also on JTpca and Tpeca intervals in nonclinical studies. These potential confounding effects may be relevant to the interpretation of ECG data obtained from nonclinical drug safety studies with Beagle dogs.

11.
Sci Rep ; 10(1): 14892, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913210

RESUMO

The incidence and mortality of primary liver cancer are very high and resection of tumor is the most crucial treatment for it. We aimed to assess the efficacy and safety of combined use of transversus abdominis plane (TAP) block and laryngeal mask airway (LMA) during implementing Enhanced Recovery After Surgery (ERAS) programs for patients with primary liver cancer. This was a prospective, evaluator-blinded, randomized, controlled parallel-arm trial. A total of 96 patients were enrolled (48 in each group). Patients in the control group received general anesthesia with endotracheal intubation, while patients in the TAP + LMA group received general anesthesia with LMA and an ultrasound-guided subcostal TAP block. The primary end-point was postoperative time of readiness for discharge. The secondary end-points were postoperative pain intensity, time to first flatus, quality of recovery (QoR), complications and overall medical cost. Postoperative time of readiness for discharge in the TAP + LMA group [7 (5-11) days] was shorter than that of the control group [8 (5-13) days, P = 0.004]. The postoperative apioid requirement and time to first flatus was lower in the TAP + LMA group [(102.8 ± 12.4) µg, (32.7 ± 5.8) h, respectively] than the control group [(135.7 ± 20.1) µg, P = 0.000; (47.2 ± 7.6) h, P = 0.000; respectively]. The QoR scores were significantly higher in the TAP + LMA group than the control group. The total cost for treatment in the TAP + LMA group [(66,608.4 ± 6,268.4) CNY] was lower than that of the control group [(84,434.0 ± 9,436.2) CNY, P = 0.000]. There was no difference in complications between these two groups. The combined usage of a TAP block and LMA is a simple, safe anesthesia method during implementing ERAS programs for patients with primary liver cancer. It can alleviate surgical stress, accelerate recovery and reduce medical cost.

12.
J Ethnopharmacol ; 266: 113394, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32941971

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract, consisting of ulcerative colitis (UC) and Crohn's disease (CD). Gut microbiota and their metabolites may play a role in the pathogen of IBD, especially of the UC. Qingchang Huashi Formula (QHF), a traditional Chinese medicine formula, has shown therapeutic effect on treating UC based on the clinical practice without clear pharmacological mechanism. AIM OF THE STUDY: The aim of this study was to clearly define the effect of QHF and its components, Baitouweng (PBR) and Baizhi (ADR) on treating UC. MATERIALS AND METHODS: Pharmacodynamic effects of QHF and single herb were evaluated in dextran sulfate sodium (DSS) induced acute or chronic colitis mice. Body weight loss, disease activity index (DAI) and colon length were estimated. Histological changes were observed by H&E staining. The number and abundance of gut microbiota were measured with 16S rRNA sequencing. LC-MS and GC-MS were used to detect the concentration of metabolites (e.g., bile acids (BAs) and short chain fatty acids (SCFAs)). The goblet cell was observed by Alcian blue/periodic acid-Schiff (AB/PAS) straining and the crypt stem cell was estimated by immunohistochemical analyses. The colorectal tissues were used to detect levels of IL-1ß, IL-6 and TNF-α by ELISA or qRT-PCR. The expression of NLRP3, Caspase 1 and IL-1ß were examined by western blotting. RESULTS: QHF significantly inhibited colitis, protected mice from the loss of body weight and colon shorten. Comparatively, ADR and PBR showed strong efficacy in inhibiting DSS-induced colitis. We verified that while ADR was responsible for QHF's effect on maintaining gut microbiota homeostasis and metabolism, PBR was more prominent in keeping crypt stem cells proliferation and colonic goblet cells function. Moreover, we demonstrated that the alleviation of colitis by QHF was associated with the restoration of gut microbiota-metabolism homeostasis, protection of intestinal epithelial barrier and regulation of NLRP3/IL-1ß pathway. CONCLUSIONS: The finding of the present study suggested that QHF is curative in DSS-induced colitis by restoring gut microbiota-metabolism homeostasis and goblet cells function. An optimized QHF was constituted by ADR and PBR, which showed comparable efficacy on colitis to that of QHF. Our work probed out the active constitutes as well as the relevant pharmacological mechanisms of QHF, shedding light on potential new drug combination for the treatment of IBD.

13.
Surg Innov ; : 1553350620954581, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32873180

RESUMO

Liver surgery has entered the era of precision surgery. Therefore, how to optimize the resection of lesions and reduce the unnecessary time of liver ischemia and hypoxia have become the focus. A total of 11 patients who underwent fluorescence laparoscopic liver mass resection and preoperative three-dimensional (3D) reconstruction between August 2018 and July 2020 were evaluated. Liver cirrhosis occurred in 3 patients. The mean intraoperative blood loss was 166.8 ± 105.7 mL. The average length of the operation time was 152.0 ± 45.3 minutes. The average intraoperative hilar occlusion time was 9.3 minutes (except for hilar cholangiocarcinoma). The liver function of all patients, except patients with hilar bile duct carcinoma, returned to the preoperative level at 72 hours, and no serious complications occurred. 3D reconstruction combined with fluorescence laparoscopic imaging is safe and effective for precision liver resection.

14.
Biomed Res Int ; 2020: 5914502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904518

RESUMO

Background: This systematic review and meta-analysis assessed the role of teriparatide in improving hip fracture healing and function to provide a clinical guide. Methods: The systematic literature review identified randomized controlled trials (RCTs) and controlled studies evaluating teriparatide for elderly hip fractures. A meta-analysis was performed using RevMan version 5.3. Results: This study included two RCTs and four retrospective studies comprising 607 patients, with 269 and 338 patients in the teriparatide and control groups, respectively. The quality of these six studies was moderate. Compared to the control group, teriparatide reduced the time to union (weighted mean difference (WMD) = -1.95; 95% confidence interval (CI): -3.23--0.68; P = 0.003) but did not improve the rate of fracture union at 3 months (odds ratio (OR) = 1.46; 95% CI: 0.50-4.24; P = 0.49) or 6 months (OR = 0.89; 95% CI: 0.44-1.81; P = 0.75). In addition, teriparatide did not decrease the complications, need for reoperation, mortality, rate of deformity after fracture healing, and subsequent fracture or improve hip function. Conclusions: The current limited evidence did not support that teriparatide improves fracture healing in hip fractures, due to study heterogeneity and various sources of biases. Further high-quality, large-sample trials are needed. This trial is registered with PROSPERO with registration number CRD42020152205.

15.
Vet Microbiol ; 249: 108834, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32919197

RESUMO

The H9N2 avian influenza virus (AIV) causes serious economic losses to the poultry industry every year. Vaccines that induce a mucosal immune response may be successful against influenza virus infection because its transmission occurs primarily in the mucosa. To develop novel and potent oral vaccines based on Lactobacillus plantarum (L. plantarum) to control the spread of AIV in poultry industry, in the present study, we constructed and expressed fusions of the influenza antigens NP and M2 with the Salmonella Typhimurium flagellinprotein FliC on the surface of L. plantarum. Oral immunization of chicks was performed, and serum antibodies, mucosal antibodies, and specific cellular immunity were detected. Immunizing chicks with avian influenza virus was evaluated. The results showed high levels of IgG in addition to high levels of secretory immunoglobulin A (sIgA) in chickens orally administered recombinant L. plantarum. In addition, the fusion may significantly increase the levels of NP- and M2-specific T cell-mediated immunity in the case of mucosal administration of NC8-pSIP409-pgsA'-NP-M2-FliC. Recombinant NC8-pSIP409-pgsA'-NP-M2-FliC mediated effectively protected chickens against influenza virus and reduced virus titers in the lung. Our study outcomes indicate that the expression of influenza NP-M2 and a mucosal adjuvant (FliC), by L. plantarum could generate a mucosal vaccine candidate for animals in the future to defend against AIVs.

16.
Pharm Nanotechnol ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32895048

RESUMO

BACKGROUND: Cationic liposomes (CLs) based messenger RNA (mRNA) vaccine has been a promising approach for cancer treatment. However, rapid lung accumulation after intraveous injection and significently decreased transfection efficacy (TE) in serum substantially hamper its application. OBJECTIVE: In this study, we attempt to investigate fate of Mannose-PEG1000-lipoplex (MP1000-LPX) in vivo, a previous reported mRNA vaccine, and potential mechanism in it. METHODS: MP1000-CLs and different type of MP1000-LPX were produced by previous method and characterized by dynamic light scattering (DLS). Organ distribution and Luc-mRNA expression of DiD loaded luciferase (Luc-mRNA)- MP1000-LPX were evaluated by IVIS Spectrum imaging system. Cellular transfection and uptake under serum-free and serum-containing conditions were analysed by flow cytometry and counted by FlowJo software. RESULTS: MP1000-CLs had an average size of 45.3 ± 0.9 nm, a positive charge of 39.9 ± 0.9 mV. When MP1000-LPX formed, the particle size increased to about 130 nm, and zeta potential decreased to about 30 mV. All formulations were in narrow size distribution with PDI < 0.3. 6 h after intraveous injection, Luc-MP1000-LPX mostly distributed to liver, lung and spleen, while only successfully expressed Luc in lung. DC2.4 cellular transfection assay indicated serum substantially lowered TE of MP1000-LPX. However, the cellular uptake on DC2.4 cells was enhanced in the presence of serum. CONCLUSION: MP1000-LPX distributed to spleen but failed to transfect. Because serum dramatically decreased TE of MP1000-LPX on DC2.4 cells, but not by impeding its interaction to cell membrane. Serum resistance and avoidance of lung accumulation might be prerequisites for CLs based intravenous mRNA vaccines.

17.
Biomed Environ Sci ; 33(8): 583-592, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933610

RESUMO

Objective: To screen the differentially expressed proteins (DEPs) in human bronchial epithelial cells (HBE) treated with atmospheric fine particulate matter (PM 2.5). Methods: HBE cells were treated with PM 2.5 samples from Shenzhen and Taiyuan for 24 h. To detect overall protein expression, the Q Exactive mass spectrometer was used. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Perseus software were used to screen DEPs. Results: Overall, 67 DEPs were screened in the Shenzhen sample-treated group, of which 46 were upregulated and 21 were downregulated. In total, 252 DEPs were screened in the Taiyuan sample-treated group, of which 134 were upregulated and 118 were downregulated. KEGG analysis demonstrated that DEPs were mainly enriched in ubiquitin-mediated proteolysis and HIF-1 signal pathways in Shenzhen PM 2.5 samples-treated group. The GO analysis demonstrated that Shenzhen sample-induced DEPs were mainly involved in the biological process for absorption of various metal ions and cell components. The Taiyuan PM 2.5-induced DEPs were mainly involved in biological processes of protein aggregation regulation and molecular function of oxidase activity. Additionally, three important DEPs, including ANXA2, DIABLO, and AIMP1, were screened. Conclusion: Our findings provide a valuable basis for further evaluation of PM 2.5-associated carcinogenesis.


Assuntos
Poluentes Atmosféricos/análise , Brônquios/metabolismo , Células Epiteliais/metabolismo , Expressão Gênica/efeitos dos fármacos , Material Particulado/análise , Brônquios/efeitos dos fármacos , Biologia Computacional , Células Epiteliais/efeitos dos fármacos , Humanos , Espectrometria de Massas , Tamanho da Partícula , Proteômica
18.
Cell Reprogram ; 22(5): 244-253, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32936029

RESUMO

Mouse embryonic stem cells (mESCs) go through self-renewal in the existence of the cytokine leukemia inhibitory factor (LIF). LIF is added to the mouse stem cells culture medium, and its removal results in fast differentiation. Dimethyl sulfoxide (DMSO) is one of the most used solvents in drug test. We exposed 4-day mESC cultures to different concentrations of DMSO (0.1%, 0.5%, 1.0%, and 2.0%) to identify the safest dose exhibiting efficacy as a solvent. mESCs grown under general pluripotency conditions in the absence of LIF were treated with DMSO. In addition, as a control for differentiation, mESCs were grown in the absence of LIF. DMSO upregulated the mRNA expression level of pluripotency markers. Moreover, DMSO reduced the mRNA expression levels of ectodermal marker (ß-tubulin3), mesodermal marker (Hand1), and endodermal markers (Foxa2 and Sox17) in mESCs. These results indicate that DMSO treatment enhances the pluripotency and disrupts the differentiation of mESCs. We also show that members of the Tet oncogene family are critical to inhibiting the differentiation and methylation of mESCs. DMSO is appropriate to sustain the pluripotency of mESCs in the absence of LIF, and that mESCs can be sustained in an undifferentiated state using DMSO. Therefore, DMSO may, in part, function as a substitute for LIF.

19.
Mol Oncol ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32813937

RESUMO

Liver metastasis is the main cause of colorectal cancer (CRC)-related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long-term daily administrations of recombinant DNase I, we have developed an adeno-associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV-mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV-DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV-DNase I and AAV-null treatments. Our data suggest that AAV-mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.

20.
Fish Physiol Biochem ; 46(6): 2037-2053, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32767005

RESUMO

Plant proteins are suitable and alternative to fish meals (FMs), with less cost compared with that of all other types of fish feeds. In recent years, soy protein concentrate (SPC) has emerged as a cost-effective alternative to FM; however, little is known regarding the effects of dietary SPC on general fish physiology and well-being. This study aimed to perform comprehensive physiological and transcriptomic analysis for testing the applicability of SPC as fish feeds in hybrid grouper (Epinephelus fuscoguttatus♀ נE. lanceolatus♂) [SPC replaced 0% (CK), 30% (SPC30), and 75% (SPC75) of FM protein]. Generally, SPC30 promoted fish survival and had less effects on the phenotype, while SPC75 reduced fish survival, promoted inflammation, and regulated multiple physiological responses. Thousands of differentially expressed genes (DEGs) by SPC were identified in the intestine, liver, and muscle, which were enriched in biological regulation, cellular process, metabolic process, single-organism process, cell, cell part, membrane, binding, and catalytic activity based on RNA-seq. Notably, some DEGs involved in amino acid and lipid metabolism in the digestive system highlighted the modulatory effect of SPC on these metabolic processes, consistent with the physiological responses including enzyme activities. The enriched aspects of these predominant DEGs might be directly related to the different effects of SPC30 and SPC75 on fish growth, digestibility, and underlying enzyme activities and histology. In conclusion, the comprehensive physiological and transcriptomic comparative analysis of CK, SPC30, and SPC75 was also effective in testing the applicability of SPC as fish feeds and in designing a proper diet with the best impact on the growth performance and health of fish in hybrid grouper.

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