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1.
Clin Exp Rheumatol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33822701

RESUMO

OBJECTIVES: No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF. METHODS: A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analysed by a mix-effects model. RESULTS: A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, p<0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, p=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (p=0.003), 12 (p=0.013), and 24 (p=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2(1)=4.59, p=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage >600 mg/day (p=0.010) and medication course >12 months (p=0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (p=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock. CONCLUSIONS: Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

2.
Microbiol Res ; 248: 126747, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33740671

RESUMO

The host-selective ACT toxin is essential for the pathogenesis of the citrus fungal pathogen Alternaria alternata. However, the mechanism of ACT-toxin gene clusters ACT-toxin biosynthesis regulated by is still poorly understood. The biosynthesis of ACT toxin is mainly regulated by multiple ACT toxin genes located in the secondary metabolite gene cluster. In this study, we reported a transcription regulator ACTR contributes ACT toxin biosynthesis through mediating ACT toxin synthesis gene ACTS4 in Alternaria alternata. We generated ACTR-disrupted and -silenced mutants in the tangerine pathotype of A. alternata. Phenotype analysis showed that the ACTR mutants displayed a significant loss of ACT toxin production and a decreased virulence on citrus leaves whereas the vegetative growth and sporulation were not affected, indicating an essential role of ACTR in both ACT toxin biosynthesis and pathogenicity. To elucidate the transcription network of ACTR, we performed RNA-Seq experiments on wild-type and ACTR null mutant and identified genes that were differentially expressed between two genotypes. Transcriptome profiling and RT-qPCR analysis demonstrated that the ACT toxin biosynthetic gene ACTS4 is down-regulated in ACTR mutant. We generated ACTS4 knock-down mutant and found that the pathogenicity of ACTS4 mutant was severely impaired. Interestingly, both ACTR and ACTS4 are not involved in the response to different abiotic stresses including oxidative stress, salt stress, cell-wall disrupting regents, and metal ion stress, indicating the function of these two genes is highly specific. In conclusion, our results highlight the important regulatory role of ACTR in ACT toxin biosynthesis through mediating ACT toxin synthesis gene ACTS4 and underline the essential role of in the tangerine pathotype of A. alternata.

3.
Elife ; 102021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752802

RESUMO

The inflammatory environment of demyelinated lesions in multiple sclerosis (MS) patients contributes to remyelination failure. Inflammation activates a cytoprotective pathway, the integrated stress response (ISR), but it remains unclear whether enhancing the ISR can improve remyelination in an inflammatory environment. To examine this possibility, the remyelination stage of experimental autoimmune encephalomyelitis (EAE), as well as a mouse model that incorporates cuprizone-induced demyelination along with CNS delivery of the proinflammatory cytokine IFN-γ were used here. We demonstrate that either genetic or pharmacological ISR enhancement significantly increased the number of remyelinating oligodendrocytes and remyelinated axons in the inflammatory lesions. Moreover, the combined treatment of the ISR modulator Sephin1 with the oligodendrocyte differentiation enhancing reagent bazedoxifene increased myelin thickness of remyelinated axons to pre-lesion levels. Taken together, our findings indicate that prolonging the ISR protects remyelinating oligodendrocytes and promotes remyelination in the presence of inflammation, suggesting that ISR enhancement may provide reparative benefit to MS patients.

4.
Mikrochim Acta ; 188(4): 113, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677619

RESUMO

A fluorescence platform is designed based on aggregation-induced emission of Au/Cu nanoclusters (Au/Cu NCs) driven by pH value. When pH increases from 6.0 to 7.0, Au/Cu NCs change from aggregation to dispersion, accompanied by the oxidation of Cu cores. Under the catalysis of urease, urea is hydrolysed to release ammonia, which further undergoes a hydrolysis reaction to produce OH-, causing the pH to increase. The fluorescence of Au/Cu NCs quenches linearly at 590 nm with the excitation wavelength at 320 nm when the concentration of urea varies from 5.0 to 100 µM. The limit of detection (LOD) and limit of quantification (LOQ) of urea are 2.23 and 7.45 µM, respectively. Combined with headspace single-drop microextraction technology, Au/Cu NCs are employed to monitor dissolved ammonia with low-cost and simple operation. The linear range of dissolved ammonia is from 20 to 300 µM. The LOD and LOQ of dissolved ammonia are 7.04 and 23.4 µM, respectively. The relative standard deviation (RSD) values of the intra-day and inter-day precision of urea are 2.4-3.0% and 3.0-3.7%, respectively, and those of dissolved ammonia are in the range 3.4-5.1% (intra-day precision) and 4.2-5.8% (inter-day precision). No interferences have been indentified in the determination of urea and dissolved ammonia. Finally, the proposed method has been applied to determine urea in human urine samples and dissolved ammonia in water samples with satisfactory results.Graphical abstract The pH increase produces the dispersion and decomposition of Au/Cu NCs, leading to the fluorescence quenching. Both urea and dissolved ammonia are detected successfully because they cause the pH change to alkaline.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33689393

RESUMO

Alternaria brown spot (ABS) caused by Alternaria alternata is an economically important fungal disease of citrus worldwide. The ABS pathogen A. alternata tangerine pathotype can produce a host-specific ACT toxin, which is regulated by ACT toxin gene cluster located in the conditionally dispensable chromosome (CDC). Previously, we have assembled a draft genome of A. alternata tangerine pathotype strain Z7, which comprises 165 contigs. In this study, we report a chromosome-level genome assembly of A. alternata Z7 through the combination of Oxford nanopore sequencing and Illumina sequencing technologies. The assembly of A. alternata Z7 had a total size of 34.28 Mb, with a GC content of 51.01% and contig N50 of Mb. The genome is encompassed 12067 protein-coding genes, 34 rRNAs, and 107 tRNAs. Interestingly, A. alternata Z7 is composed of 10 essential chromosomes (ECs) and 2 conditionally dispensable chromosomes (CDCs), which is consistent with the experimental evidences of pulsed-field gel electrophoresis (PFGE). To our best knowledge, this is the first chromosome-level genome assembly of A. alternata. In addition, a database for citrus-related Alternaria genomes has been established to provide public resources for the sequences, annotation and comparative genomics data of Alternaria species. The improved genome sequence and annotation at the chromosome level is a significant step toward a better understanding of the pathogenicity of A. alternata. The database will be updated regularly whenever the genomes of newly isolated Alternaria species are available. The citrus-related Alternaria genomes database is open accessible through http://www.zjudata.com/alternaria/blast.php.

6.
Medicine (Baltimore) ; 100(11): e24565, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725938

RESUMO

ABSTRACT: To determine the effect of earthquake on sleep quality of adults who had experienced Tangshan Earthquake either as infants or fetuses and also investigate whether CRHR1 polymorphism influenced sleep quality in subjects exposed to seismic stress.Totally 556 subjects were enrolled in the current study and were divided into 3 groups, those who had experienced Tangshan Earthquake as infants (group I) or fetuses (group II), and those who had not experienced Tangshan Earthquake (group III). Sleep was evaluated using the Pittsburgh Sleep Quality Index (PQSI). Three single nucleotide polymorphisms of the CRHR1 gene were analyzed.Fifty two (9.4%) subjects had sleep disturbance, including 17 (9.9%) subjects in group I, 24 (13.4%) subjects in group II, and 11 (5.3%) subjects in group III (χ2 = 7.373, P = .025). Moreover, subjects with CRHR1 genotype T/T had a significantly lower rate of sleep disturbance (7.8%) than subjects with genotype C/T and C/C (14.7%; χ2 = 4.845, P  = .028). Furthermore, subjects with rs7209436 genotype C had an approximately 2-fold increase in the risk of sleep disturbance versus those who were not genotype C (OR = 1.978, 95% CI (1.045, 3.744).Prenatal and postnatal exposure to seismic stress significantly increases subsequent risk of sleep disturbance in adulthood.


Assuntos
Terremotos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/genética , Receptores de Hormônio Liberador da Corticotropina/genética , Transtornos do Sono-Vigília/genética , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância , Desastres , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Gravidez , Fatores de Risco , Sono/genética
7.
Water Res ; 194: 116964, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33652228

RESUMO

Drinking water treatment plants (DWTPs) produce filter backwash water (FBW) and sedimentation sludge water (SSW) that may be partially recycled to the head of DWTPs. The impacts of key disinfection conditions, water quality parameters (e.g., disinfection times, disinfectant types and doses, and pH values), and bromide concentration on controlling the formation of trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), and haloacetamides (HAMs) during disinfection of FBW and SSW were investigated. Concentrations of most disinfection byproducts (DBPs) and associated calculated toxicity increased with extended chlorination for both FBW and SSW. During chlorination of both FBW and SSW, elevated chlorine doses significantly increased THM yields per unit dissolved organic carbon (DOC), but decreased HAN and HAM yields, with minimum effect on HAA yields. Chloramine disinfection effectively inhibited C-DBP formation but promoted N-DBPs yields, which increased with chloramine dose. Calculated toxicities after chloramination increased with chloramine dose, which was opposite to the trend found after free chlorine addition. An examination of pH effects demonstrated that C-DBPs were more readily generated at alkaline pH (pH=8), while acidic conditions (pH=6) favored N-DBP formation. Total DBP concentrations increased at higher pH levels, but calculated DBP toxicity deceased due to lower HAN and HAM concentrations. Addition of bromide markedly increased bromo-THM and bromo-HAN formation, which are more cytotoxic than chlorinated analogues, but had little impact on the formation of HAAs and HAMs. Bromide incorporation factors (BIFs) for THMs and HANs from both water samples all significantly increased as bromide concentrations increased. Overall, high bromide concentrations increased the calculated toxicity values in FBW and SSW after chlorination. Therefore, while currently challenging, technologies capable of removing bromide should be explored as part of a strategy towards controlling cumulative toxicity burden (i.e., hazard) while simultaneously lowering individual DBP concentrations (i.e., exposure) to manage DBP risks in drinking water.


Assuntos
Desinfetantes , Água Potável , Poluentes Químicos da Água , Purificação da Água , Cloro , Desinfetantes/análise , Desinfecção , Halogenação , Esgotos , Trialometanos , Poluentes Químicos da Água/análise
8.
Nat Neurosci ; 24(2): 234-244, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33526922

RESUMO

Fibrosis is a common pathological response to inflammation in many peripheral tissues and can prevent tissue regeneration and repair. Here, we identified persistent fibrotic scarring in the CNS following immune cell infiltration in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Using lineage tracing and single-cell sequencing in EAE, we determined that the majority of the fibrotic scar is derived from proliferative CNS fibroblasts, not pericytes or infiltrating bone marrow-derived cells. Ablating proliferating fibrotic cells using cell-specific expression of herpes thymidine kinase led to an increase in oligodendrocyte lineage cells within the inflammatory lesions and a reduction in motor disability. We further identified that interferon-gamma pathway genes are enriched in CNS fibrotic cells, and the fibrotic cell-specific deletion of Ifngr1 resulted in reduced fibrotic scarring in EAE. These data delineate a framework for understanding the CNS fibrotic response.


Assuntos
Barreira Hematoencefálica/patologia , Encefalomielite Autoimune Experimental/patologia , Fibroblastos/patologia , Fibrose/patologia , Infiltração de Neutrófilos , Medula Espinal/patologia , Animais , Camundongos , Oligodendroglia/patologia
10.
ISME J ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452476

RESUMO

Arsenic pollution is a widespread threat to marine life, but the ongoing rise pCO2 levels is predicted to decrease bio-toxicity of arsenic. However, the effects of arsenic toxicity on marine primary producers under elevated pCO2 are not well characterized. Here, we studied the effects of arsenic toxicity in three globally distributed diatom species (Phaeodactylum tricornutum, Thalassiosira pseudonana, and Chaetoceros mulleri) after short-term acclimation (ST, 30 days), medium-term exposure (MT, 750 days), and long-term (LT, 1460 days) selection under ambient (400 µatm) and elevated (1000 and 2000 µatm) pCO2. We found that elevated pCO2 alleviated arsenic toxicity even after short acclimation times but the magnitude of the response decreased after mid and long-term adaptation. When fed with these elevated pCO2 selected diatoms, the scallop Patinopecten yessoensis had significantly lower arsenic content (3.26-52.83%). Transcriptomic and biochemical analysis indicated that the diatoms rapidly developed arsenic detoxification strategies, which included upregulation of transporters associated with shuttling harmful compounds out of the cell to reduce arsenic accumulation, and upregulation of proteins involved in synthesizing glutathione (GSH) to chelate intracellular arsenic to reduce arsenic toxicity. Thus, our results will expand our knowledge to fully understand the ecological risk of trace metal pollution under increasing human activity induced ocean acidification.

11.
Sci Total Environ ; 769: 144698, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33493910

RESUMO

Although the influence of environmental factors on the microbial community in water sources is crucial, it is seldom evaluated. The seasonal relationship between microbial diversity of bacteria and fungi and environmental factors was investigated in a large drinking-water reservoir using Illumina MiSeq sequencing. Forty-one bacterial phyla and nine fungal phyla were analyzed in the Qingcaosha Reservoir, Shanghai, China. The predominant bacterial phyla were Actinobacteria, Proteobacteria, Bacteroidetes, and Cyanobacteria, with the maximum relative abundance of 46%, 36.6%, 16.1%, and 14.9%, respectively. Actinobacteria were observed to be the predominant bacterial phylum during spring and summer. The maximum relative abundance of unclassified fungi appeared in summer (98.8%), which was higher than that of Ascomycota and Basidiomycota (11.7% and 8.2%, respectively). Principal coordinate analysis (PCoA) results showed that the structural similarity in the bacterial community was greater during summer and winter; however, the fungal community exhibited a greater similarity during spring and summer. 2-Methylisoborneol (2-MIB), an olfactory compound produced by microorganisms, was detected at a concentration of 8.97 ng/L during summer, which was slightly lower than the olfactory threshold (10 ng/L). The positive correlation between Actinobacteria and unclassified fungi and 2-MIB (p < 0.05) confirmed that Actinobacteria and unclassified fungi produced 2-MIB. The chemical oxygen demand (COD) was 1.48-1.94 mg/L, and the maximum concentrations of total nitrogen (TN) and total phosphorus (TP) were 2.1 mg/L and 0.5 mg/L, respectively. Chloroflexi were negatively correlated with COD (p < 0.05) but positively correlated with TP (p < 0.01). Nitrospirae were negatively correlated with COD (p < 0.05), but positively correlated with TN (p < 0.05). Among the classified fungi, Rozellomycota, Basidiomycota (p < 0.05), and Chytridiomycota (p < 0.01) were positively correlated with TP. Therefore, the relative abundance of predominant bacteria was affected by various environmental factors; however, fungi were mainly influenced by TP.


Assuntos
Microbiota , Micobioma , Bactérias/genética , China , Água
12.
Nutrition ; 81: 110940, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32755743

RESUMO

OBJECTIVES: The aim of the present study was to investigate the potential of pterostilbene, a beneficial component primarily found in blueberries, to alleviate the intrauterine growth retardation (IUGR)-induced early liver injury and oxidative stress in a porcine model. METHODS: Thirty-six IUGR piglets and an equal number of normal birth weight (NBW) counterparts received a diet with or without pterostilbene (250 mg/kg diet) during the first week post-weaning. Parameters related to the hepatic injury, oxidative stress, and antioxidant defense mechanisms were analyzed. RESULTS: Relative to NBW, IUGR induced liver injury, which corresponded to increments in circulating alanine transaminase activity and hepatic apoptotic cell rate, superoxide radical generation, and the accumulation of oxidative damage products (P < 0.05). Administering pterostilbene reduced plasma transaminase activities, decreased hepatocyte apoptosis rate, and prevented the augmented levels of hepatic superoxide anion, 8-hydroxy-2 deoxyguanosine, and 4-hydroxynonenal-modified protein (P < 0.05). In terms of the hepatic antioxidant function, pterostilbene was efficient in improving the superoxide dismutase activity and the metabolic cycle between reduced glutathione and its oxidized form (P < 0.05). The pterostilbene-supplemented diet facilitated the nuclear translocation of nuclear factor erythroid-2-related factor 2 (NRF2) and promoted the expression levels of superoxide dismutase 2 in the liver of IUGR piglets (P < 0.05). CONCLUSION: This study indicates that pterostilbene treatment has an auxiliary therapeutic potential to ameliorate early liver injury in IUGR neonates, presumably by stimulating the NRF2 signals and the associated antioxidant function.

14.
Environ Pollut ; : 116038, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33280915

RESUMO

Soil ecological risk caused by compound pollutants is a topic that deserves increasing attention, and soil risk early warning is a more in-depth discussion on this topic. In this study, we collected soil samples from Changchun, a typical industrial city, and determined the contents of 13 heavy metals (HMs) (0.00 mg kg-1-6380 mg kg-1), 16 polycyclic aromatic hydrocarbons (PAHs) (0.00 mg kg-1-27.7 mg kg-1), 7 polychlorinated biphenyls (PCBs) (0.30 µg kg-1-168 µg kg-1), and 8 organochlorine pesticides (OCPs) (0.00 mg kg-1-4.52 mg kg-1). The soil ecological risks of compound pollutants were assessed. The results showed that PAHs were the greatest risk pollutants, followed by PCBs and HMs, and OCPs were the smallest risk pollutants. Most of the ecological risks of compound pollutants were classified as "moderate severity" level according to the (contamination severity index) CSI evaluation criteria. With the help of modern industrial economic theory, through the analysis of the annual accumulation of pollutants, it is possible to predict the future pollutant content in Changchun, and the soil risks could be forewarned. The results showed that if active measures were not taken to reduce the accumulation of PAHs in Changchun soil, the CSI-PAHs would be classified as "ultra-high severity" level in 2035.

15.
Front Cell Neurosci ; 14: 599717, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192332

RESUMO

Multiple Sclerosis (MS) is an immune-mediated neurological disorder, characterized by central nervous system (CNS) inflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Although autoimmunity, inflammatory demyelination and neurodegeneration underlie MS, the initiating event has yet to be clarified. Effective disease modifying therapies need to both regulate the immune system and promote restoration of neuronal function, including remyelination. The challenge in developing an effective long-lived therapy for MS requires that three disease-associated targets be addressed: (1) self-tolerance must be re-established to specifically inhibit the underlying myelin-directed autoimmune pathogenic mechanisms; (2) neurons must be protected from inflammatory injury and degeneration; (3) myelin repair must be engendered by stimulating oligodendrocyte progenitors to remyelinate CNS neuronal axons. The combined use of chronic and relapsing remitting experimental autoimmune encephalomyelitis (C-EAE, R-EAE) ("outside-in") as well as progressive diphtheria toxin A chain (DTA) and cuprizone autoimmune encephalitis (CAE) ("inside-out") mouse models allow for the investigation and specific targeting of all three of these MS-associated disease parameters. The "outside-in" EAE models initiated by myelin-specific autoreactive CD4+ T cells allow for the evaluation of both myelin-specific tolerance in the absence or presence of neuroprotective and/or remyelinating agents. The "inside-out" mouse models of secondary inflammatory demyelination are triggered by toxin-induced oligodendrocyte loss or subtle myelin damage, which allows evaluation of novel therapeutics that could promote remyelination and neuroprotection in the CNS. Overall, utilizing these complementary pre-clinical MS models will open new avenues for developing therapeutic interventions, tackling MS from the "outside-in" and/or "inside-out".

16.
J Orthop Surg Res ; 15(1): 504, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138838

RESUMO

BACKGROUND: The accuracy of targeted lower limb alignment correction following HTO is closely related to patients' pain relief and knee joint survival time. How to accurately perform osteotomy and how to obtain the ideal target limb alignment to maximize the curative effect are the difficulty in HTO practice. The purpose of this study is to evaluate the predictive and application value of osteotomy master software (OsteoMaster) in coronal plane preoperative planning of high tibial osteotomy. METHOD: Sixty-seven patients with medial compartment osteoarthritis and varus deformity treated by medial open-weight high tibial osteotomy were enrolled and divided into observation group (31 cases) and control group (36 cases). The observation group was planned by OsteoMaster, while the control group was planned by Miniaci. The preoperative predicted values of osteotomy depth, open height, correction angle, WBL ratio, and FTA of the observation group were compared with the actual intraoperative values to study their accuracy. The operative time, blood loss, number of fluoroscopy, and WBL ratio were compared between the observation group and the control group to study its application value. RESULT: There was no significant difference between two groups in preoperative prediction and intraoperative reality of osteotomy depth, open height, correction angle, FTA, and WBL ratio (P > 0.05). The operation time and number of fluoroscopy in the observation group were significantly less than those in the control group (P < 0.05), while the difference in blood loss was not statistically significant (P > 0.05). The good rate of WBL ratio was 87.1% in the observation group and 75% in the control group. CONCLUSION: OsteoMaster has predictive value in osteotomy depth, open height, correction angle, FTA, and WBL ratio of HTO, which is also helpful to reduce the number of fluoroscopy, shorten the operation time, and improve the accuracy of target limb alignment. The drawback of this approach is 2-dimensional approach in contrast to 3-dimensional preoperative planning that is including the more real study.

17.
Int J Exp Pathol ; 101(6): 223-229, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33146446

RESUMO

The transforming growth factor beta (TGF-ß) superfamily plays an important role in cancer development. One aspect of this is that the transforming growth factor beta receptor III (TGFBR3) is frequently overexpressed in some tumours. However, the role of TGFBR3 in oesophageal squamous cell carcinoma (ESCC) has not been explored as yet. In this study, we aimed to determine the role of TGFBR3 in the development and prognosis of ESCC and the correlation between TGFBR3 expression and Ki-67 and p53. Immunohistochemistry was performed to investigate the expression of TGFBR3 in the tumour tissue microarray consisting of ESCC tissues and matched adjacent normal tissues (n = 80). Only ESCC tissues (n = 20) were also used in our analysis. The association between TGFBR3 expression and clinicopathological characteristics, such as Ki-67 and p53, was analysed by Spearman's rank correlation coefficient analysis. The association between TGFBR3 expression and prognosis of ESCC was analysed using Kaplan-Meier analysis and log-rank tests. The expression levels of TGFBR3 in oesophageal cancer tissues were markedly higher than in matched adjacent normal tissues. Furthermore, TGFBR3 overexpression was significantly associated with tumour-node-metastasis (TNM) stage, lymph node metastasis (N stage) and Ki-67 expression. However, TGFBR3 overexpression was not significantly related to age, sex or p53. In univariate analysis, overall survival of ESCC patients was significantly associated with high TGFBR3 expression, sex, T stage, N stage and TNM stage. Moreover, ESCC patients with high TGFBR3 expression had poorer overall survival than those with low TGFB R3 expression. Our findings showed that TGFBR3 was upregulated in the development of human ESCC and high TGFBR3 expression was associated with high expression of Ki-67 and poor prognosis of ESCC. Therefore, TGFBR3 may be a valuable prognostic marker and a novel therapeutic target for ESCC.

18.
Oxid Med Cell Longev ; 2020: 7178123, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101591

RESUMO

Intrauterine growth retardation (IUGR) delays the gut development of neonates, but effective treatment strategies are still limited. This study used newborn piglets as a model to evaluate the protective effect of polydatin (PD) against IUGR-induced intestinal injury. In total, 36 IUGR piglets and an equal number of normal birth weight (NBW) littermates were fed either a basal diet or a PD-supplemented diet from 21 to 35 days of age. Compared with NBW, IUGR induced jejunal damage and barrier dysfunction of piglets, as indicated by observable bacterial translocation, enhanced apoptosis, oxidative and immunological damage, and mitochondrial dysfunction. PD treatment decreased bacterial translocation and inhibited the IUGR-induced increases in circulating diamine oxidase activity (P = 0.039) and D-lactate content (P = 0.004). The apoptotic rate (P = 0.024) was reduced by 35.2% in the PD-treated piglets, along with increases in villus height (P = 0.033) and in ratio of villus height to crypt depth (P = 0.049). PD treatment promoted superoxide dismutase (P = 0.026) and glutathione S-transferase activities (P = 0.006) and reduced malondialdehyde (P = 0.015) and 8-hydroxy-2'-deoxyguanosine accumulation (P = 0.034) in the jejunum. The PD-treated IUGR piglets showed decreased jejunal myeloperoxidase activity (P = 0.029) and tumor necrosis factor alpha content (P = 0.035) than those received a basal diet. PD stimulated nuclear sirtuin 1 (P = 0.028) and mitochondrial citrate synthase activities (P = 0.020) and facilitated adenosine triphosphate production (P = 0.009) in the jejunum of piglets. Furthermore, PD reversed the IUGR-induced declines in mitochondrial DNA content (P = 0.048), the phosphorylation of adenosine monophosphate-activated protein kinase alpha (P = 0.027), and proliferation-activated receptor gamma coactivator 1 alpha expression (P = 0.033). Altogether, the results indicate that PD may improve jejunal integrity, mitigate mucosal oxidative and immunological damage, and facilitate mitochondrial function in IUGR piglets.

19.
J Mol Cell Biol ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049034

RESUMO

Metastases are the main cause of cancer-related mortality in breast cancer. Although significant progress has been made in the field of tumor metastasis, the exact molecular mechanisms involved in tumor metastasis are still unclear. Here, we report that ATOH8-V1, a novel isoform of ATOH8, is highly expressed in breast cancer and is a negative prognostic indicator of survival for patients. Forced expression of ATOH8-V1 dramatically enhances, while silencing of ATOH8-V1 decreases the metastasis of breast cancer cell lines. Moreover, ATOH8-V1 directly binds to the RhoC promoter and stimulates the expression of RhoC, which in turn enhances the metastasis of breast cancer. Altogether, our data demonstrate that ATOH8-V1 is a novel pro-metastatic factor that enhances cancer metastasis, suggesting that ATOH8-V1 is a potential therapeutic target for treatment of metastatic cancers.

20.
J Anim Sci ; 98(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027517

RESUMO

This investigation evaluated the potential of natural antioxidants, pterostilbene (PT) and its parent compound resveratrol (RSV), to alleviate hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in early-weaned piglets. A total of 144 suckling piglets were randomly assigned to four treatments (six replicates per group, n = 6): 1) sow reared, 2) early weaned and fed a basal diet, 3) early weaned and fed the basal diet supplemented with 300 mg/kg PT, or with 4) 300 mg/kg RSV. Early weaning increased plasma alanine aminotransferase (P = 0.004) and aspartate aminotransferase (P = 0.009) activities and hepatic apoptotic rate (P = 0.001) in piglets compared with the sow-reared piglets. Early weaning decreased hepatic adenosine triphosphate (ATP; P = 0.006) content and mitochondrial complexes III (P = 0.019) and IV activities (P = 0.038), but it increased superoxide anion accumulation (P = 0.026) and the expression levels of ER stress markers, such as glucose-regulated protein 78 (P < 0.001), CCAAT/enhancer-binding protein-homologous protein (P = 0.001), and activating transcription factor (ATF) 4 (P = 0.006). PT was superior to RSV at mitigating liver injury and oxidative stress after early weaning, as indicated by decreases in the number of apoptotic cells (P = 0.036) and the levels of superoxide anion (P = 0.002) and 8-hydroxy-2 deoxyguanosine (P < 0.001). PT increased mitochondrial deoxyribonucleic acid content (P = 0.031) and the activities of citrate synthase (P = 0.005), complexes I (P = 0.004) and III (P = 0.011), and ATP synthase (P = 0.041), which may contribute to the mitigation of hepatic ATP deficit (P = 0.017) in the PT-treated weaned piglets. PT also prevented increases in the ER stress marker and ATF 6 expression levels and in the phosphorylation of inositol-requiring enzyme 1 alpha caused by early weaning (P < 0.05). PT increased sirtuin 1 activity (P = 0.031) in the liver of early-weaned piglets than those in the early-weaned piglets fed a basal diet. In conclusion, PT supplementation alleviates liver injury in weanling piglets probably by inhibiting mitochondrial dysfunction and ER stress.

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