Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 585
Filtrar
1.
Chemosphere ; 274: 129744, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33540308

RESUMO

Though sulfamethoxazole (SMX) degradation at the low or medium concentration (SMX< 30 mg/L) has been reported in the microbial fuel cell (MFC), further exploration is still urgently required to investigate how the high concentration of SMX affect the anode biofilm formation. In this study, the degradation mechanism of SMX and the response of microbial community to SMX at different initial concentrations (0, 0.5, 5 and 50 mg/L) were investigated in MFCs. The highest SMX removal efficiency of 98.4% was obtained in MFC (5 mg/L). SMX at optimal concentration (5 mg/L) could serve as substrate accelerating the extracellular electron transfer. However, high concentration of SMX (50 mg/L) conferred significant inhibition on the electron transfer with SMX removal decline to 84.4%. The 16S rRNA high-throughput sequencing revealed the significant shift of the anode biofilms communities with different initial SMX concentrations were observed in MFCs. Thauera and Geobacter were the predominant genus, with relative abundance of 31.9% in MFC (50 mg/L SMX) and 52.7% in MFC (5 mg/L SMX). Methylophilus exhibited a huge increase with the highest percentage of 16.4% in MFC (50 mg/L). Hence, the functional bacteria of Thauera, Geobacter and Methylophilus endowed significant tolerance to the selection pressure from high concentration of SMX in MFCs. Meanwhile, some bacteria including Ornatilinea, Dechloromonas and Longilinea exhibited a decrease or even disappeared in MFCs. Therefore, initial concentrations of SMX played a fundamental role in modifying the relative abundance of predominant populations. This finding would promote theories support for understanding the evolution of anode biofilm formation related to the different initial concentrations of SMX in MFCs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33406007

RESUMO

Liver fibrosis, a major cause of morbidity and mortality worldwide, leads to liver damage, seriously threatening human health. In our previous study, we demonstrated that 14-kDa phosphohistidine phosphatase (PHP14) was upregulated in fibrotic liver tissue and involved in the migration and lamellipodia formation of hepatic stellate cells (HSCs). In this study, we evaluated PHP14 as a therapeutic target for liver fibrosis and investigated the mechanism by which it mediates liver fibrosis. AAV-shPhpt1 administration significantly attenuates CCl4-induced liver fibrosis in mice. In particular, fibrosis-associated inflammatory infiltration was significantly suppressed after PHP14 knockdown. Mechanistically, PHP14 regulated macrophage recruitment, infiltration and migration by affecting podosome formation of macrophages. Inhibition of PHP14 decreased the expression of the fibrogenic signature at the early stage of liver fibrogenesis and the activation of HSCs in vivo. Thus, PHP14 can be considered a potential therapeutic target for liver fibrosis.

3.
Theranostics ; 11(3): 1079-1099, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391522

RESUMO

Background: The host-parasite relationship is based on subtle interplay between parasite survival strategies and host defense mechanisms. It is well known that helminth infection, which afflicts more than one billion people globally, correlates with a decreased prevalence of obesity. Dissecting the underlying mechanisms can provide new targets for treating obesity from the host-parasite interaction perspective. Methods: C57BL/6 mice received a normal or high-fat diet (HFD) with or without Sjp40 (one main component of schistosome-derived soluble egg antigens) treatment. Both the loss and gain-of-function experiments by the inhibitor suppression and lentivirus treatment of miR-802 were utilized to elucidate the role of miR-802/AMPK axis in host lipid metabolism. Hepatocyte lipogenesis assay and metabolic parameters were assessed both in vivo and in vitro. The potential interactions among Sjp40, CD36, miR-802, Prkab1, and AMPK were clarified by pull-down, miRNA expression microarray, quantitative RT-PCR, dual-luciferase reporter assay, and western blotting analysis. Results: We showed a link between decreased miR-802 and impaired lipid metabolism in Schistosoma japonicum infected mice. The decreased miR-802 promotes murine Prkab1 or human Prkaa1 expression, respectively, which increases levels of phosphorylated AMPK, resulting in a decrease in hepatic lipogenesis. Also, injection with schistosome-derived soluble egg antigens (SEA) attenuated metabolism. We demonstrated that Sjp40 as a main component of SEA interacted with CD36 on hepatocytes to inhibit miR-802, resulting in the activation of AMPK pathway and subsequent attenuation of lipogenesis. Collectively: Our study reveals the significant role of miR-802/AMPK axis in hepatic lipid metabolism and identifies the therapeutic potential of Sjp40 in treating obesity-related fatty liver.

5.
Ecotoxicol Environ Saf ; 208: 111570, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396099

RESUMO

Traditional brominated flame retardants (BFRs) negatively affect the environment and human health, especially in the sensitive (developing) nervous system. Considering the physicochemical similarities between novel brominated flame retardants (NBFRs) and BFRs, more and more evidence reveals the neurotoxic effects of NBFRs. We reviewed the neuro(endocrine) toxic effects of NBFRs in vivo and in vitro and discussed their action mechanisms based on the available information. The neurotoxic potential of NBFRs has been demonstrated through direct neurotoxicity and disruption of the neuroendocrine system, with adverse effects on neurobehavioral and reproductive development. Mechanistic studies have shown that the impact of NBFRs is related to the complex interaction of neural and endocrine signals. From disrupting the gender differentiation of the brain, altering serum thyroid/sex hormone levels, gene/protein expression, and so on, to interfere with the feedback effect between different levels of the HPG/HPT axis. In this paper, the mechanism of neurotoxic effects of NBFRs is explored from a new perspective-neuro and endocrine interactions. Gaps in the toxicity data of NBFRs in the neuroendocrine system are supplemented and provide a broader dataset for a complete risk assessment.


Assuntos
Sistema Endócrino/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Retardadores de Chama/toxicidade , Monitoramento Ambiental , Éteres Difenil Halogenados/análise , Humanos , Hidrocarbonetos Bromados/análise , Síndromes Neurotóxicas/metabolismo , Medição de Risco , Hormônios Tireóideos
6.
Cell Death Dis ; 12(1): 69, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33431817

RESUMO

Radioresistance is the main obstacle in the clinical management of nasopharyngeal carcinoma (NPC). linc00312 is deregulated in a number of human cancers, including NPC. However, the detailed functions and underlying mechanisms of linc00312 in regulating radiosensitivity of NPC remains unknown. In this study, cox regression analysis was used to assess the association between linc00312 and NPC patients' survival after radiotherapy. Our results reveal that linc00312 is significantly down-regulated in NPC tissues and patients with higher expression of linc00312 are significantly associated with longer overall survival and better short-term radiotherapy efficacy. Overexpression of linc00312 could increase the sensitivity of NPC cells to ionizing radiation, as indicated by clonogenic survival assay, comet assay, and flow cytometry. Mechanistically, RNA pull down and RNA immunoprecipitation were performed to investigate the binding proteins of linc00312. linc00312 directly binds to DNA-PKcs, hinders the recruitment of DNA-PKcs to Ku80, and inhibits phosphorylation of AKT-DNA-PKcs axis, therefore inhibiting the DNA damage signal sensation and transduction in the NHEJ repair pathway. In addition, linc00312 impairs DNA repair and cell cycle control by suppressing MRN-ATM-CHK2 signal and ATR-CHK1 signal. In summary, we identified DNA-PKcs as the binding protein of linc00312 and revealed a novel mechanism of linc00312 in the DNA damage response, providing evidence for a potential therapeutic strategy in NPC.

7.
Hepatol Int ; 15(1): 82-92, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33460002

RESUMO

BACKGROUND AND AIMS: Many models have been developed to predict liver-related events (LRE) in chronic hepatitis B, few focused on compensated HBV-induced cirrhosis. We aimed to describe the incidence of LRE and to determine independent risk predictors of LRE in compensated HBV-induced cirrhosis patients receiving antiviral therapy using routinely available parameters. METHODS: Prospective cohorts of treatment-naïve adults with compensated HBV-induced cirrhosis were enrolled. Patients were treated with entecavir (ETV) or ETV + thymosin-alpha1 (Thy-α1) or lamivudine (LAM) + adefovir (ADV). Data were collected at baseline and every 6 months. LRE was defined as development of decompensation, HCC or death. RESULTS: Totally 937 patients were included, 608 patients treated with ETV, 252 with ETV + Thy-α1, and 77 with LAM + ADV. After a median follow-up of 4.5 years, 88 patients developed LRE including 48 with HCC. The cumulative incidence of LRE at year 1, 3, and 5 was 2.1%, 7.0%, and 12.7%, respectively, and was similar for three treatment groups. All models using variables at month 6 or 12 had better fit than models using baseline values. The best model for prediction of LRE used PLT, GGT, and AFP at month 6 [AUC: 0.762 (0.678-0.814)], for hepatic decompensation-PLT, LSM and GGT at month 12 (AUC: 0.834 (0.675-0.919)), and for HCC-AFP and GGT at month 6 [AUC 0.763 (0.691-0.828)]. All models had negative predictive values of 94.0-98.8%. CONCLUSION: Models using on-treatment variables are more accurate than models using baseline variables in predicting LRE in patient with compensated HBV-induced cirrhosis receiving antiviral therapy. ClincialTrials.gov number NCT01943617, NCT01720238, NCT03366571, NCT02849132.

8.
Chemosphere ; 262: 128352, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182087

RESUMO

As organic pollution of soil and groundwater increases, the effective and economical remediation of contaminated sites has drawn growing attention. In this study, running-water (RW) was designed to modify alkali-heat/persulfate (MAH/PS) for integrated remediation of an actual organic-contaminated site. The degradation efficiency mainly reached 60%-99% for Benz[a]anthracene, Benzo[a]pyrene and total petroleum hydrocarbons (TPHs). MAH/PS was more effective in degrading Benzene and 1,2-Dichloroethane with simple molecular configurations. The pollutant degradation efficiencies decreased with increasing site depth and increased with increasing pollutant concentrations. Migration with RW enhanced site remediation. By monitoring the groundwater after remediation, it was found that residual TPHs presented anomalous diffusion; SO42- ranged from 8.00 to 237.00 mg L-1 to 8.00-290.00 mg L-1 and pH presented alkalescence (7.00-8.20). Mathematical models were established to describe the reaction process including the solubility equilibrium of calcium hydroxide, temperature equilibrium, and reaction kinetics. Moreover, MAH/PS provided a cost-saving approach for site remediation.


Assuntos
Recuperação e Remediação Ambiental/métodos , Poluentes do Solo/análise , Poluentes do Solo/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Álcalis , Benzo(a)pireno/química , China , Água Subterrânea/análise , Água Subterrânea/química , Temperatura Alta , Hidrocarbonetos/química , Modelos Teóricos , Oxirredução , Petróleo/análise , Poluição por Petróleo , Solo/química , Sulfatos/química
9.
Eur J Pharm Sci ; 158: 105683, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347980

RESUMO

Diacylglycerol acyltransferase 1 (DGAT1) plays a pivotal role in lipid metabolism by catalyzing the committed step in triglyceride (TG) synthesis and has been considered as a potential therapeutic target of multiple metabolic diseases, including dyslipidemia, obesity and type 2 diabetes. Here we report a novel DGAT1 inhibitor, Yhhu2407, which showed a stronger DGAT1 inhibitory activity (IC50 = 18.24 ± 4.72 nM) than LCQ908 (IC50 = 78.24 ± 8.16 nM) in an enzymatic assay and led to a significant reduction in plasma TG after an acute lipid challenge in mice. Pharmacokinetic studies illustrated that Yhhu2407 displayed a low systemic, liver- and intestine-targeted distribution pattern, which is consistent with the preferential tissue expression pattern of DGAT1 and therefore might help to maximize the beneficial pharmacological effects and prevent the occurrence of side effects. Cell-based investigations demonstrated that Yhhu2407 inhibited free fatty acid (FFA)-induced TG accumulation and apolipoprotein B (ApoB)-100 secretion in HepG2 cells. In vivo study also disclosed that Yhhu2407 exerted a beneficial effect on regulating plasma TG and lipoprotein levels in rats, and effectively ameliorated high-fat diet (HFD)-induced dyslipidemia in hamsters. In conclusion, we identified Yhhu2407 as a novel DGAT1 inhibitor with potent efficacy on improving lipid metabolism in rats and HFD-fed hamsters without causing obvious adverse effects.

10.
FASEB J ; 35(1): e21205, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33337558

RESUMO

CRISPR/Cas9-mediated genome editing shows cogent potential for the genetic modification of helminth parasites. We report successful gene knock-in (KI) into the genome of the egg of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We edited the acetylcholinesterase (AChE) gene of S. mansoni targeting two guide RNAs (gRNAs), X5 and X7, located on exon 5 and exon 7 of Smp_154600, respectively. Eggs recovered from livers of experimentally infected mice were transfected by electroporation with a CRISPR/Cas9-vector encoding gRNA X5 or X7 combining with/ without a ssODN donor. Next generation sequencing analysis of reads of amplicon libraries spanning targeted regions revealed that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). Furthermore, soluble egg antigen from AChE-edited eggs exhibited markedly reduced AChE activity, indicative that programed Cas9 cleavage mutated the AChE gene. Following injection of AChE-edited schistosome eggs into the tail veins of mice, an significantly enhanced Th2 response involving IL-4, -5, -10, and-13 was detected in lung cells and splenocytes in mice injected with X5-KI eggs in comparison to control mice injected with unmutated eggs. A Th2-predominant response, with increased levels of IL-4, -13, and GATA3, also was induced by X5 KI eggs in small intestine-draining mesenteric lymph node cells when the gene-edited eggs were introduced into the subserosa of the ileum of the mice. These findings confirmed the potential and the utility of CRISPR/Cas9-mediated genome editing for functional genomics in schistosomes.

11.
Technol Health Care ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33285652

RESUMO

BACKGROUND: Robot-assisted therapy (RT) has become a promising stroke rehabilitation intervention. OBJECTIVE: To examine the effects of short-term upper limb RT on the rehabilitation of sub-acute stroke patients. METHODS: Subjects were randomly assigned to the RT group (n= 23) or conventional rehabilitation (CR) group (n= 22). All subjects received conventional rehabilitation therapy for 30 minutes twice a day, for 2 weeks. In addition, the RT group received RT for 30 minutes twice a day, for 2 weeks. The outcomes before treatment (T0) and at 2 weeks (T1) and 1 month follow-up (T2) were evaluated in the patients using the upper limb motor function test of the Fugl-Meyer assessment (FMA) the Motricity Index (MI), the Modified Ashworth Scale (MAS), the Functional Independence Measure (FIM), and the Barthel Index (BI). RESULTS: There were significant improvements in motor function scales (P< 0.001 for FMA and MI) and activities of daily living (P< 0.001 for FIM and BI) but without muscle tone (MAS, P> 0.05) in the RT and CR groups. Compared to the CR group, the RT group showed improvements in motor function and activities of daily living (P< 0.05 for FMA, MI, FIM, BI) at T1 and T2. There was no significant difference between the two groups in muscle tone (MAS, P> 0.05). CONCLUSIONS: RT may be a useful tool for sub-acute stroke patients' rehabilitation.

12.
Liver Int ; 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-33277803

RESUMO

BACKGROUND & AIMS: Non-invasive assessment criteria to rule out high-risk varices (HRV) in compensated hepatitis B virus (HBV) cirrhosis on antiviral therapy remains unclear. METHODS: HBV-related compensated cirrhotic patients underwent screening endoscopy during antiviral therapy were enrolled and randomly divided into the derivation and validation sets. HRV were defined as medium to large varices or small varices with red signs. Univariate and multivariate logistic analysis were used to determine the parameters associated with HRV. RESULTS: A total of 436 HBV-related compensated cirrhotic patients screened for varices were enrolled, the median duration of antiviral therapy was 4 years (IQR: 2.5-5.5 years). In the derivation set (N = 290, 17.2% with HRV), only platelet (PLT) count (OR = 0.972, 95% CI 0.961-0.984, P <0.05) was independently associated with HRV, whereas liver stiffness measurement was not associated with the presence of HRV. With a PLT count cut-off value of 105 x109 /L, unnecessary endoscopies could be spared in 56.9% patients, with a 3.6%. risk of missing HRV. In the validation cohort (N = 146, 16.4% with HRV), the proportion of patients that could safely spare endoscopies (61.0%) identified by this PLT count cut-off value was higher than that obtained by using Baveno VI criteria (34.9%), with an acceptable risk of missing HRV (3.4%). CONCLUSION: Compared with the "Baveno VI criteria or beyond" criteria, PLT count higher than 105 x109 /L could safely spare more screening endoscopies without increasing the risk of missing HRV in patients with HBV-related compensated cirrhosis on antiviral therapy.

13.
Gastric Cancer ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159601

RESUMO

BACKGROUND: Aberrant activation of Wnt/ß-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/ß-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity. METHODS: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/ß-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of ß-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo. RESULTS: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with ß-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase ß-Trcp1 for ß-catenin binding, thereby decreasing ß-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner ß-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with ß-catenin expression levels. CONCLUSIONS: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/ß-catenin signaling via SHARPIN-mediated stabilization of ß-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive ß-catenin signaling in a subset of human gastric cancers.

14.
Mol Cancer Res ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172976

RESUMO

AXL, a TAM family receptor tyrosine kinase, is increasingly being recognized as a key determinant of resistance to targeted therapies as well as chemotherapy and radiation in non-small cell lung cancer (NSCLC) and other cancers. We further show here that high levels of AXL and EMT were frequently expressed in subsets of both treatment-naïve and treatment-relapsed NSCLC. Previously, we and others have demonstrated a role for AXL in mediating DNA damage repair (DDR) as well as resistance to inhibition of WEE1, a replication stress response kinase. Here, we show that BGB324 (bemcentinib), a selective small-molecule AXL inhibitor, caused DNA damage and induced replication stress, indicated by ATR/CHK1 phosphorylation, more significantly in TP53-deficient NSCLC cell lines. Similar effects were also observed in large cell neuroendocrine carcinoma (LCNEC) cell lines. High AXL protein levels were also associated with resistance to ATR inhibition. Combined inhibition of AXL and ATR significantly decreased cell proliferation of NSCLC and LCNEC cell lines. Mechanistically, combined inhibition of AXL and ATR significantly increased RPA32 hyper-phosphorylation and DNA double strand breaks and induced markers of mitotic catastrophe. Notably, NSCLC cell lines with low levels of SLFN11, a known predictive biomarker for platinum and PARP inhibitor sensitivity, were more sensitive to AXL/ATR co-targeting. These findings demonstrate a novel and unexpected role for AXL in replication stress tolerance, with potential therapeutic implications. Implications: These findings demonstrate that the combination of AXL and ATR inhibitors could be a promising therapeutic combination for NSCLC, LCNEC and other cancers.

15.
Int Immunopharmacol ; 88: 106968, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182058

RESUMO

Alcohol-induced liver injury is characterized by abnormal liver dysfunction and excessive inflammation response. Recent years a wealth of data have been yielded indicating that EtOH (ethyl alcohol)-induced macrophage activation along with liver inflammation plays a dominating role in the progression of alcohol-induced liver injury. Here we found high expression of NLRP12 (Nucleotide-binding oligomerization domain protein 12, which is generally considered to be a negative regulator of inflammatory response) in EtOH-fed mouse liver tissue, primary Kupffer cells and EtOH-induced RAW264.7 cells. Additionally, overexpression of NLRP12 following Ad (adenovirus)-NLRP12-EGFP contributed to the attenuation of steatosis and inflammation in EtOH-fed mice model and EtOH-primed RAW264.7 cells. In parallel, Knockdown of NLRP12 aggravated the inflammatory response in RAW264.7 cells triggered by EtOH. Meanwhile, after administration of overexpression or inhibition of NLRP12 expression in vitro, the expression of phosphorylated protein of NF-kB signaling pathway was significantly affected. After increasing or decreasing the expression of NLRP12 in RAW264.7 cells, AML-12 cells were cultured with the supernatant of RAW264.7 cells stimulated by EtOH, and the percent of apoptosis ratio of AML-12 cells was remarkably altered. The study suggested that reduced inflammatory response induced by NLRP12-mediated inhibition of NF-kB pathway participated in the decrease of hepatocyte apoptosis in alcohol-induced liver injury. Collectively, these findings suggested the significance of NLRP12-mediated macrophage activation in alcohol-induced liver injury.

16.
Bioessays ; : e2000185, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33145822

RESUMO

Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9-targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming issues involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9-mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration.

17.
Brain Res ; 1748: 147082, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32866544

RESUMO

Neovascularization is a histological feature of glioma, especially of glioblastoma (GBM), being associated with tumor invasiveness and poor prognosis. However, current anti-angiogenic therapies targeting vascular endothelial cells (ECs), has exhibited poor efficacy in some GBM cases. This may be at least partially attributed to the potential of glioblastoma cells to construct blood supply chain via vasculogenic mimicry or endothelial differentiation. This study aims to explore differences in vasculogenic activity and sensitivity to angiogenic stimulants between normal human ECs and glioma cells of different grades. We found that grade IV U87 GBM cells showed highly inducible vasculogenic activity either in the orthotopic xenograft model or under in vitro angiogenic stimulants as compared with grade II CHG5 glioma cells. The hypoxia mimetic more strongly induced in vitro vasculogenic capacity and endothelial marker expression of U87 GBM cells than the stimulation with multiple proangiogenic growth factors (vascular endothelial growth factor, basic fibroblast growth factor and epidermal growth factor). In contrast, proangiogenic effect of hypoxia on human umbilical vein endothelial cells (HUVECs) was weaker than on U87 GBM cells. In addition, it was also observed that the in vitro vasculogenic process of U87 cells started later but lasted longer than that of HUVECs. These results demonstrate that when compared with normal ECs, high-grade glioma cells basically possess weaker vasculogenic activity, but exhibit higher sensitivity and longer-lasting response to angiogenic stimulants, especially to hypoxia. This may be helpful to develop novel anti-angiogenic strategies targeting both vascular ECs and vasculogenic glioma cells.

18.
Mol Biochem Parasitol ; 240: 111322, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961206

RESUMO

Morbidity associated with hepatic and urogenital schistosomiasis stems primarily from the host immune response directed against schistosome eggs. When eggs become entrapped in host tissues, the development of fibrotic plaques drives downstream pathology. These events occur due to the antigenic nature of egg excretory/secretory products (ESPs). Both Schistosoma mansoni and S. japonicum ESPs have been shown to interact with several cell populations in the host liver including hepatocytes, macrophages, and hepatic stellate cells, with both immunomodulatory and pathological consequences. Several protein components of the ESPs of S. mansoni and S. japonicum eggs have been characterised; however, studies into the collective contents of schistosome egg ESPs are lacking. Utilising shotgun mass spectrometry and an array of in silico analyses, we identified 266, 90 and 50 proteins within the S. mansoni, S. japonicum and S. haematobium egg secretomes respectively. We identified numerous proteins with already established immunomodulatory activities, vaccine candidates and vesicle markers. Relatively few common orthologues within the ESPs were identified by BLAST, indicating that the three egg secretomes differ in content significantly. Having a clearer understanding of these components may lead to the identification of new proteins with uncharacterised immunomodulatory potential or pathological relevance. This will enhance our understanding of host-parasite interactions, particularly those occurring during chronic schistosomiasis, and pave the way towards novel therapeutics and vaccines.

19.
Int J Biol Macromol ; 164: 3771-3779, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32891645

RESUMO

DNA methylation is an important epigenetic modification and has been shown to be involved in the response to abiotic stress. However, there are few studies on DNA methylation in insect response to environmental signals. In this study, we conducted a comprehensive comparative analysis of DNA methylation profiles between two silkworm strains with significantly different resistance to heat and humidity by whole-genome bisulfite sequencing (WGBS). We identified, in total, 2934 differentially methylated regions (DMRs) between RT_48h (resistant strain with high-temperature/humidity treatment for 48 h) and ST_48h (sensitive strain with high-temperature/humidity treatment for 48 h) under cytosine context (CG), which corresponded to 1230 DMR-related genes (DMGs), and the DMRs were primarily located in the gene body (exon and intron) region. Gene ontology (GO) and KEGG analysis showed that these DMGs were most significantly enriched in binding, cellular metabolic process, and RNA transport pathways. Moreover, 10 DMGs have been revealed to be involved in the heat-humidity stress response in the silkworm. The results of this study indicated that DNA methylation plays crucial roles in silkworm response to environmental stressors and provides important clues to identify key resistance genes in silkworm under high-temperature/humidity stress response.

20.
Medicine (Baltimore) ; 99(39): e22425, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991477

RESUMO

Some scholars' studies have demonstrated that Pro-kin balance system training is able to promote the recovery of the balance function in stroke patients. The present study has expanded on those studies, and was not merely limited to studying balance, but also encompassed walking and self-care abilities of the patients; furthermore, the association among balance and walking and self-care abilities was also explored.A total of 40 stroke patients were randomly and equally divided into 2 groups: the control group (n = 20) and the treatment group (n = 20). Both groups underwent conventional balance training, although the treatment group also underwent visual feedback balance training with the Pro-kin system. The balance function was assessed using the Berg Balance Scale (BBS), the Timed "Up & Go" (TUG) test, and Pro-kin system parameters. The Pro-kin system parameters included the perimeter and ellipse area, which were both tested once with eyes open (EO) and eyes closed (EC). Walking ability was assessed using the Holden Walking Ability Scale, according to the Functional Ambulation Classification (FAC). The self-care abilities were assessed with the Barthel Index (BI). The tests were conducted prior to training, and 3 weeks after the end of the training programme.No significant differences were noted among the groups before the training. After 3 weeks of training, for both the groups, significant improvements in balance and the walking and self-care abilities were noted: The BBS value was significantly increased (P < .05), whereas the TUG, perimeter, and ellipse area with EO and EC measurements were significantly decreased after treatment (P < .05). The FAC and BI readings were significantly increased after treatment (P < 0.05), and the treatment group outperformed the control group (P < .05). Furthermore, the balance function was shown to be strongly correlated with the walking and self-care abilities (P < .01).The present study has demonstrated that the use of the Pro-kin visual feedback balance training system in combination with conventional training is a viable method for improving walking and self-care abilities of stroke patients.


Assuntos
Retroalimentação Sensorial , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autocuidado , Caminhada
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...