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1.
J Mol Biol ; : 166963, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33811917

RESUMO

While cytosolic Hsp90 chaperones have been extensively studied, less is known about how the ER Hsp90 paralog Grp94 recognizes clients and influences client folding. Here, we examine how Grp94 and the ER Hsp70 paralog, BiP, influence the folding of insulin-like growth factor 2 (IGF2), an established client protein of Grp94. ProIGF2 is composed of a disulfide-bonded insulin-like hormone and a C-terminal E-peptide that has sequence characteristics of an intrinsically disordered region. BiP and Grp94 have a minimal influence on folding whereby both chaperones slow proIGF2 folding and do not substantially alter the disulfide-bonded folding intermediates, suggesting that BiP and Grp94 may have an additional influence unrelated to proIGF2 folding. Indeed, we made the unexpected discovery that the E-peptide region allows proIGF2 to form dynamic oligomers. ProIGF2 oligomers can transition from a dynamic state that is capable of exchanging monomers to an irreversibly aggregated state, providing a plausible role for BiP and Grp94 in regulating proIGF2 oligomerization. In contrast to the modest influence on folding, BiP and Grp94 have a stronger influence on proIGF2 oligomerization and these chaperones exert counteracting effects. BiP suppresses proIGF2 oligomerization while Grp94 can enhance proIGF2 oligomerization in a nucleotide-dependent manner. We propose that BiP and Grp94 regulate the assembly and dynamic behavior of proIGF2 oligomers, although the biological role of proIGF2 oligomerization is not yet known.

2.
Anim Sci J ; 92(1): e13548, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33835647

RESUMO

The purpose of this study was to investigate the effect of the E1 activating enzyme UBA2 on the expression of the SUMO-1 protein during in vitro maturation (IVM) of pig oocytes and embryonic development. In the 5 µg/ml UBA2 treatment group, the expression of the anti-apoptotic gene Bcl-2 and the embryo cleavage rate was significantly increased, while the proapoptotic gene Bax was significantly reduced. When 10 µg/ml UBA2 was added, the in vitro maturation rate, blastocyst rate, and SUMO-1 protein content of oocytes increased significantly (p < .05), and the expression of proapoptotic gene Caspase3 was significantly decreased (p < .05), while the viability of cumulus cells was extremely significantly reduced (p < .01). In summary, UBA2 can regulate the content of the SUMO-1 protein in mature pig oocytes in vitro, which in turn affects the maturation rate of oocytes, expression of apoptosis genes, cumulus cell viability, and the development of embryos after fertilization.

3.
BMJ Open ; 11(4): e042006, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827830

RESUMO

OBJECTIVES: To describe the prevalence of modifiable risk factors for upper digestive tract cancer (UDTC) and its coprevalence, and investigate relevant influencing factors of modifiable UDTC risk factors coprevalence among residents aged 40-69 years in Yangzhong city, China. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 21 175 participants aged 40-69 years were enrolled in the study. 1962 subjects were excluded due to missing age, marital status or some other selected information. Eventually, 19 213 participants were available for the present analysis. MAIN OUTCOMES MEASURES: Prevalence and coprevalence of eight modifiable UDTC risk factors (overweight or obesity, current smoking, excessive alcohol consumption, insufficient vegetables intake, insufficient fruit intake and the consumption of pickled, fried and hot food) were analysed. RESULTS: The prevalence of overweight/obesity, current smoking, excessive alcohol consumption, insufficient vegetables intake, insufficient fruit intake and the consumption of pickled, fried and hot food in this study was 45.3%, 24.1%, 16.2%, 66.1%, 94.5%, 68.1%, 36.0% and 88.4%, respectively. Nearly all (99.9%) participants showed one or more UDTC risk factors, 98.6% of the participants showed at least two risk factors, 92.2% of the participants had at least three risk factors and 69.7% of the participants had four or more risk factors. Multivariate logistic regression analysis revealed that men, younger age, single, higher education, higher annual family income and smaller household size were more likely to present modifiable UDTC risk factors coprevalence. CONCLUSIONS: The prevalence and coprevalence of modifiable UDTC risk factors are high among participants in Yangzhong city. Extra attention must be paid to these groups who are susceptible to risk factors coprevalence during screening progress. Relative departments also need to make significant public health programmes that aim to decrease modifiable UDTC risk factors coprevalence among residents aged 40-69 years from high-risk areas of UDTC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33830378

RESUMO

To improve the operational stability of glucose isomerase in E. coli TEGI-W139F/V186T, the immobilized cells were prepared with modified diatomite as a carrier and 74.1% activity of free cells was recovered after immobilization. Results showed that the immobilized cells still retained 86.2% of the initial transformational activity after intermittent reused 40 cycles and the yield of D-fructose reached above 42% yield at 60 °C. Moreover, the immobilized cells were employed in the continuous production of High Fructose Corn Syrup (HFCS) in a recirculating packed bed reactor for 603 h at a constant flow rate. It showed that the immobilized cells exhibited good operational stability and the yield of D-fructose retained above 42% within 603 h. The space-time yield of high fructose corn syrup reached 3.84 kg L-1 day-1. The investigation provided an efficient immobilization method for recombinant cells expressing glucose isomerase with higher stability, and the immobilized cells are a promising biocatalyst for HFCS production.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33780343

RESUMO

Most of the recent image segmentation methods have tried to achieve the utmost segmentation results using large-scale pixel-level annotated data sets. However, obtaining these pixel-level annotated training data is usually tedious and expensive. In this work, we address the task of semisupervised semantic segmentation, which reduces the need for large numbers of pixel-level annotated images. We propose a method for semisupervised semantic segmentation by improving the confidence of the predicted class probability map via two parts. First, we build an adversarial framework that regards the segmentation network as the generator and uses a fully convolutional network as the discriminator. The adversarial learning makes the prediction class probability closer to 1. Second, the information entropy of the predicted class probability map is computed to represent the unpredictability of the segmentation prediction. Then, we infer the label-error map of the segmentation prediction and minimize the uncertainty on misclassified regions for unlabeled images. In contrast to existing semisupervised and weakly supervised semantic segmentation methods, the proposed method results in more confident predictions by focusing on the misclassified regions, especially the boundary regions. Our experimental results on the PASCAL VOC 2012 and PASCAL-CONTEXT data sets show that the proposed method achieves competitive segmentation performance.

6.
Acta Pharmacol Sin ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782540

RESUMO

Hypertension is a serious public health problem worldwide. MT-1207, chemically named 3-(4-(4-(1H-benzotriazole-1-yl)butyl)piperazine-1-yl) benzisothiazole hydrochloride, is a new chemical entity that has entered into clinical trial as antihypertensive agent in China. In this paper we report the pharmacological profile of MT-1207 regarding its acute, subacute, and long-term effects on hypertensive animal models, and its actions on isolated organs in vitro as well as its molecular targets. Blood pressure (BP) was measured in conscious animals; amlodipine was taken as a positive control drug. We showed that both single dose of MT-1207 (1.25-20 mg/kg, ig) in spontaneously hypertensive rats (SHR) and MT-1207 (0.25-6 mg/kg, ig) in two-kidney one-clip (2K1C) dogs dose-dependently decreased BP. MT-1207 quickly decreased BP within 5 min after administration; the hypotensive effect lasted for 8 and 12 h, respectively, in SHR and 2K1C dogs without reflex increase in heart rate. Multiple doses of MT-1207 (5 mg · kg-1 · d-1 in SHR; 2 mg · kg-1 · d-1 in 2K1C dogs, for 7 days) significantly decreased BP, slightly reduced heart rate, and both of them recovered after withdrawal. Long-term administration of MT-1207 (10 mg · kg-1 · d-1 for 4 months or more time) produced a stable BP reduction, improved baroreflex sensitivity, reduced renal and cardiovascular damage in SHR, and delayed stroke occurrence and death in stroke-prone SHR. In isolated rat aortic rings precontracted by adrenaline, KCl, noradrenaline or 5-hydroxytryptamine (5-HT), MT-1207 (10-9-10-4 M) caused concentration-dependent relaxation. In a panel of enzyme activity or radioligand binding assays of 87 molecular targets, MT-1207 potently inhibited adrenergic α1A, α1B, α1D, and 5-HT2A receptors with Ki < 1 nM. The antagonism of MT-1207 against these receptors was confirmed in isolated rabbit arteries. We conclude that MT-1207 is a novel and promising single-molecule multitarget agent for hypertension treatment to reduce hypertensive organ damage and stroke mortality.

7.
J Am Heart Assoc ; 10(7): e019618, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33759542

RESUMO

Background Evidence on the differences in fracture risk associated with non-vitamin K antagonist oral anticoagulants (NOAC) and warfarin is inconsistent and inconclusive. We conducted a systematic review and meta-analysis to assess the fracture risk associated with NOACs and warfarin. Methods and Results We searched PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inception until May 19, 2020. We included studies presenting measurements (regardless of primary/secondary/tertiary/safety outcomes) for any fracture in both NOAC and warfarin users. Two or more reviewers independently screened relevant articles, extracted data, and performed quality assessments. Data were retrieved to synthesize the pooled relative risk (RR) of fractures associated with NOACs versus warfarin. Random-effects models were used for data synthesis. We included 29 studies (5 cohort studies and 24 randomized controlled trials) with 388 209 patients. Patients treated with NOACs had lower risks of fracture than those treated with warfarin (pooled RR, 0.84; 95% CI, 0.77-0.91; P<0.001) with low heterogeneity (I2=38.9%). NOACs were also associated with significantly lower risks of hip fracture than warfarin (pooled RR, 0.89; 95% CI, 0.81-0.98; P=0.023). A nonsignificant trend of lower vertebral fracture risk in NOAC users was also observed (pooled RR, 0.74; 95% CI, 0.54-1.01; P=0.061). Subgroup analyses for individual NOACs demonstrated that dabigatran, rivaroxaban, and apixaban were significantly associated with lower fracture risks. Furthermore, the data synthesis results from randomized controlled trials and real-world cohort studies were quite consistent, indicating the robustness of our findings. Conclusions Compared with warfarin, NOACs are associated with lower risks of bone fracture.

8.
Front Immunol ; 12: 637933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746977

RESUMO

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high rate of mortality and recurrence. N6-methyladenosine methylation (m6A) is the most common modification to affect cancer development, but to date, the potential role of m6A regulators in ACC prognosis is not well understood. In this study, we systematically analyzed 21 m6A regulators in ACC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. We identified three m6A modification patterns with different clinical outcomes and discovered a significant relationship between diverse m6A clusters and the tumor immune microenvironment (immune cell types and ESTIMATE algorithm). Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that the m6A clusters were strongly associated with immune infiltration in the ACC. Next, to further explore the m6A prognostic signatures in ACC, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to establish an eight-m6A-regulator prognostic model in the TCGA dataset, and the results showed that the model-based high-risk group was closely correlated with poor overall survival (OS) compared with the low-risk group. Subsequently, we validated the key modifications in the GEO datasets and found that high HNRNPA2B1 expression resulted in poor OS and event-free survival (EFS) in ACC. Moreover, to further decipher the molecular mechanisms, we constructed a competing endogenous RNA (ceRNA) network based on HNRNPA2B1, which consists of 12 long noncoding RNAs (lncRNAs) and 1 microRNA (miRNA). In conclusion, our findings indicate the potential role of m6A modification in ACC, providing novel insights into ACC prognosis and guiding effective immunotherapy.

9.
Orthop Surg ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33719200

RESUMO

OBJECTIVE: To test the significance of serum C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), the platelet count/mean platelet volume ratio (PC/MPV), plasma fibrinogen, and D-Dimer in periprosthetic joint infection (PJI) diagnosis. METHODS: We retrospectively analyzed the clinical data of 149 patients diagnosed from July 2016 to December 2019 with primary osteoarthritis (OA group, average age 63.18 years [range, 53-82 years] 18 males, 46 females), PJI (PJI group, average age 63.74 years [range, 52-81 years], 16 males, 31 females), and aseptic loosening (aseptic group, average age 63.18 years [range, 53-80 years], 12 male, 26 female) in our department. Demographic data and the sensitivity and specificity of preoperative CRP, ESR, PC/MPV, fibrinogen, and D-Dimer in PJI diagnosis were compared. RESULTS: There were no significant differences when the demographic data of the three groups were compared. The expression level of CRP (50.67 ± 58.98 mg/L), ESR (50.55 ± 25.81 mm/h), PC/MPV (35.79 ± 18.00), and fibrinogen (4.85 ± 1.33 µg/mL) in the PJI group were higher than in the OA group (CRP: 4.09 ± 9.68 mg/L; ESR:13.44 ± 9.32 mm/1 h; PC/MPV: 24.97 ± 7.58; fibrinogen: 3.09 ± 0.55 µg/mL) and the aseptic group (CRP: 7.01 ± 11.83 mg/L; ESR: 22.47 ± 17.53 mm/1 h; PC/MPV: 25.18 ± 11.48; fibrinogen: 3.39 ± 0.80 µg/mL), respectively. The expression level of plasma D-dimer (1.60 ± 1.29 mg/L) in the PJI group was higher than in the OA group (0.49 ± 0.42 mg/L) but similar to that in the aseptic group (1.21 ± 1.35 mg/L). Receiver operating characteristic (ROC) curve analysis demonstrated that the areas under the ROC curve (AUC) for CRP, ESR, PC/MPV, fibrinogen, and D-dimer were 0.892 (95% confidence interval, 0.829-0.954), 0.888 (0.829-0.947), 0.686 (0.589-0.784), 0.873 (0.803-0.943), and 0.835 (0.772-0.899), respectively. When PC/MPV > 31.70, fibrinogen >4.01 µg/mL, and D-dimer >1.17 mg/L were set as the threshold values for the diagnosis of PJI, the sensitivity of PC/MPV in PJI diagnosis was lower than that of ESR and plasma fibrinogen. In contrast, there was no significant difference when comparing the specificity of CRP, ESR, PC/MPV, fibrinogen, and D-dimer in PJI diagnosis. CONCLUSION: Plasma fibrinogen is a good new auxiliary diagnostic marker for PJI.

10.
Nat Prod Res ; : 1-4, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691545

RESUMO

Two sterols and seven triterpenoids were isolated and identified from Ganoderma lucidum by silica gel column chromatography, preparative high-performance liquid chromatography and spectra analysis. Then, the multidrug resistance reversal activities of these compounds were assessed using MTT assay. Among these compounds, ganoderol B (3), ganoderone A (4), ganodermanondiol (6) and ganoderiol F (8) were shown to reverse the resistance of human oral epidermoid carcinoma cell line KBv200 to doxorubicin, and the reversal folds were 6.59, 4.70, 4.01 and 7.09, respectively. Ganoderiol F could increase the intracellular accumulation of doxorubicin in KBv200 cells through inhibiting P-glycoprotein transport function. Further mechanistic investigation found that ganoderiol F did not alter P-glycoprotein expression. In conclusion, ganoderiol F has potent effect in reversing P-glycoprotein mediated tumor multidrug resistance. Potential reversal agents against multidrug resistance in tumor may be found in triterpenoids from Ganoderma lucidum.

11.
AMB Express ; 11(1): 34, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646434

RESUMO

To accurately explore the interaction mechanism between Escherichia coli and Staphylococcus aureus, we designed an ecological experiment to monoculture and co-culture E. coli and S. aureus. We co-cultured 45 strains of E. coli and S. aureus, as well as each species individually to measure growth over 36 h. We implemented a genome wide association study (GWAS) based on growth parameters (λ, R, A and s) to identify significant single nucleotide polymorphisms (SNPs) of the bacteria. Three commonly used growth regression equations, Logistic, Gompertz, and Richards, were used to fit the bacteria growth data of each strain. Then each equation's Akaike's information criterion (AIC) value was calculated as a commonly used information criterion. We used the optimal growth equation to estimate the four parameters above for strains in co-culture. By plotting the estimates for each parameter across two strains, we can visualize how growth parameters respond ecologically to environment stimuli. We verified that different genotypes of bacteria had different growth trajectories, although they were the same species. We reported 85 and 52 significant SNPs that were associated with interaction in E. coli and S. aureus, respectively. Many significant genes might play key roles in interaction, such as yjjW, dnaK, aceE, tatD, ftsA, rclR, ftsK, fepA in E. coli, and scdA, trpD, sdrD, SAOUHSC_01219 in S. aureus. Our study illustrated that there were multiple genes working together to affect bacterial interaction, and laid a solid foundation for the later study of more complex inter-bacterial interaction mechanisms.

12.
Aging Cell ; : e13343, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721419

RESUMO

Although important factors governing the meiosis have been reported in the embryonic ovary, meiosis in postnatal testis remains poorly understood. Herein, we first report that SRY-box 30 (Sox30) is an age-related and essential regulator of meiosis in the postnatal testis. Sox30-null mice exhibited uniquely impaired testis, presenting the abnormal arrest of germ-cell differentiation and irregular Leydig cell proliferation. In aged Sox30-null mice, the observed testicular impairments were more severe. Furthermore, the germ-cell arrest occurred at the stage of meiotic zygotene spermatocytes, which is strongly associated with critical regulators of meiosis (such as Cyp26b1, Stra8 and Rec8) and sex differentiation (such as Rspo1, Foxl2, Sox9, Wnt4 and Ctnnb1). Mechanistically, Sox30 can activate Stra8 and Rec8, and inhibit Cyp26b1 and Ctnnb1 by direct binding to their promoters. A different Sox30 domain required for regulating the activity of these gene promoters, providing a "fail-safe" mechanism for Sox30 to facilitate germ-cell differentiation. Indeed, retinoic acid levels were reduced owing to increased degradation following the elevation of Cyp26b1 in Sox30-null testes. Re-expression of Sox30 in Sox30-null mice successfully restored germ-cell meiosis, differentiation and Leydig cell proliferation. Moreover, the restoration of actual fertility appeared to improve over time. Consistently, Rec8 and Stra8 were reactivated, and Cyp26b1 and Ctnnb1 were reinhibited in the restored testes. In summary, Sox30 is necessary, sufficient and age-associated for germ-cell meiosis and differentiation in testes by direct regulating critical regulators. This study advances our understanding of the regulation of germ-cell meiosis and differentiation in the postnatal testis.

13.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668690

RESUMO

The Mongolian rhubarb-Rheum undulatum L. (RU)-and Rumex crispus L. (RC)-a Taiwanese local rhubarb belonging to the family of Polygonaceae-are principal therapeutic materials in integrative medicine due to their rich quantities of bioactive compounds; however, their phytochemical and antioxidant properties, and anti-cancer activity is poorly investigated. Furthermore, the phytochemical characteristics of both species may be affected by their different geographical distribution and climatic variance. The current study aimed to compare RU with RC extracts in different polarity solvents (n-hexane, ethyl acetate, acetone, ethanol, and water) for their phytochemical contents including the total phenolic content (TPC), total anthraquinone content (TAC), total flavonoid content (TFC), antioxidant and free radical scavenging capacities, and anticancer ability on the HepG2 cell. Except for the n-hexane extract, all of the RU extracts had considerably higher TPCs than RC extracts, ranging from 8.39 to 11.16 mg gallic acid equivalent (GAE) per gram of dry weight, and the TPCs of each extract were also significantly correlated with their antioxidant capacities by ABTS, DPPH, and FRAP assays (p < 0.05). Moreover, there was no remarkable association between the antioxidant capacities and either TACs or TFCs in both the RU and RC extracts. Besides, high-performance liquid chromatography (HPLC) analysis revealed that both the RU and RC extracts contained chrysophanol, emodin, and physcion, and those bioactive compounds were relatively higher in the n-hexane solvent extracts. Additionally, we observed different levels of dose-dependent cytotoxic effects in all the extracts by cell viability assay. Notably, the ethanol extract of RU had a compelling cytotoxic effect with the lowest half-maximum inhibition concentration (IC50-171.94 ± 6.56 µg/mL at 48 h) among the RU extracts than the ethanol extract of RC. Interestingly, the ethanol extract of RU but not RC significantly induced apoptosis in the human liver cancer cell line, HepG2, with a distinct pattern in caspase-3 activation, resulting in increased PARP cleavage and DNA damage. In summary, Mongolian Rhubarb, RU, showed more phytochemical contents, as well as a higher antioxidant capacity and apoptotic effect to HepG2 than RC; thus, it can be exploited for the proper source of natural antioxidants and liver cancer treatment in further investigation.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Rheum/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Mongólia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade , Ácidos Sulfônicos/antagonistas & inibidores , Taiwan , Células Tumorais Cultivadas
14.
Sci Total Environ ; 771: 144839, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545462

RESUMO

3-methylcholanthrene (3-MCA) is a typical representative PAH. It has strong toxicity and is a typical chemical carcinogen. However, the epigenetic mechanisms underlying 3-MCA-induced tumourigenesis are largely unknown. In this study, a model of the 3-MCA-induced malignant transformation of human bronchial epithelial (HBE) cells was established successfully. The profiles of gene expression and DNA methylation and hydroxymethylation were obtained and analysed with an Illumina HiSeq 4000. A total of 707 genes were found to be significantly up-regulated, and 686 genes were found to be significantly down-regulated. Compared to control cells, 8545 mRNA-associated differentially methylated regions and 15,121 mRNA-associated differentially hydroxymethylated regions in promoters were found to be significantly altered in transformed cells. By using mRNA expression and DNA methylation and hydroxymethylation interaction analysis, 99 differentially expressed genes were identified. Among them, CA9 and EGLN3 were verified to be significantly down-regulated, and CARD6 and LCP1 were shown to be significantly up-regulated, and these genes mainly participated in cell growth, migration and invasion, indicating that these genes were key genes involved in the 3-MCA-induced malignant transformation of HBE cells. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that a large number of differentially expressed genes (DEGs) were involved mainly in RNA polymerase II transcription factor activity, chemical carcinogenesis, base-excision repair (BER), cytokine-cytokine receptor interactions, glycerolipid metabolism, steroid hormone biosynthesis, cAMP signalling pathways and other signalling pathways. Our study suggested that characteristic gene alterations associated with DNA methylation and hydroxymethylation could play important roles in environmental 3-MCA-induced lung carcinogenesis.


Assuntos
Metilação de DNA , Metilcolantreno , Epigênese Genética , Expressão Gênica , Humanos , Pulmão
15.
J Alzheimers Dis ; 80(1): 371-381, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33554904

RESUMO

BACKGROUND: Alzheimer's disease dementia (ADD) is an important health problem in the world. OBJECTIVE: The present study investigated the validity and reliability of a new version of the Frontal Assessment Battery (FAB) named the FAB-phonemic (FAB-P). METHODS: A total of 76 patients with ADD, 107 patients with amnestic mild cognitive impairment (aMCI), 37 patients with non-amnestic MCI (naMCI), and 123 healthy controls were included in this study. All participants were evaluated with the FAB-P and the cognitive assessments according to a standard procedure. RESULTS: The global FAB-P scores in patients with ADD were lower than those of patients with aMCI, patients with naMCI, and healthy controls (p < 0.001). Patients with aMCI performed worse than healthy controls (p < 0.001). The interrater reliability, test-retest reliability, and Cronbach's alpha coefficient for the FAB-P were 0.997, 0.819, and 0.736, respectively. The test could distinguish the patients with mild ADD, aMCI, and naMCI from healthy controls with classification accuracy of 89.4%, 70.9%, and 61.6%, respectively. It could also discriminate between the patients with ADD and aMCI, between those with ADD and naMCI, and between those with aMCI and naMCI with classification accuracy of 73.8%, 83.9%, and 58.0%, respectively. The regression analysis revealed that the Montreal Cognitive Assessment and the Stroop Color Word Test Part C had the greatest contribution to FAB-P score variance. CONCLUSION: The FAB-P is a valid and reliable tool for evaluating frontal lobe function and can effectively discriminate ADD, aMCI, and naMCI.

16.
J Am Heart Assoc ; 10(5): e016437, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33586465

RESUMO

Background A higher risk of developing dementia is observed in patients with atrial fibrillation (AF). Results are inconsistent regarding the risk of dementia when patients with AF use different anticoagulants. We aimed to investigate the risk of dementia in patients with AF receiving non-vitamin K antagonist oral anticoagulants (NOACs) compared with those receiving warfarin. Methods and Results We conducted a nationwide population-based cohort study of incident cases using the Taiwan National Health Insurance Research Database. We initially enlisted all incident cases of AF and then selected those treated with either NOACs or warfarin for at least 90 days between 2012 and 2016. First-ever diagnosis of dementia was the primary outcome. We performed propensity score matching to minimize the difference between each cohort. We used the Fine and Gray competing risk regression model to calculate the hazard ratio (HR) for dementia. We recruited 12 068 patients with AF (6034 patients in each cohort). The mean follow-up time was 3.27 and 3.08 years in the groups using NOACs and warfarin, respectively. Compared with the HR for the group using warfarin, the HR for dementia was 0.82 (95% CI, 0.73-0.92; P=0.0004) in the group using NOACs. Subgroup analysis demonstrated that users of NOAC aged 65 to 74 years, with a high risk of stroke or bleeding were associated with a lower risk of dementia than users of warfarin with similar characteristics. Conclusions Patients with AF using NOACs were associated with a lower risk of dementia than those using warfarin. Further randomized clinical trials are greatly needed to prove these findings.

17.
Fam Pract ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615372

RESUMO

OBJECTIVES: To examine the validity and reliability of the Mandarin version of the Treatment Burden Questionnaire (TBQ) among stroke patients. BACKGROUND: Stroke patients need long-term management of symptoms and life situation, and treatment burden has recently emerged as a new concept that can influence the health outcomes during the rehabilitation process. METHODS: The convenience sampling method was used to recruit 187 cases of stroke patients in a tertiary grade hospital in Tianjin for a formal investigation. Item analysis, reliability and validity tests were carried out. The reliability test included internal consistency and test-retest reliability. And as well as content, structure and convergent validity were performed for the validity test. RESULTS: Of the 187 completed questionnaires, only 180 (96.3%) were suitable for analysis. According to the experts' evaluation, the I-CVI of each item was from 0.833 to 1.000, and the S-CVI was 0.967. The exploratory factor analysis yielded three-factor components with a cumulative variation of 53.054%. Convergent validity was demonstrated using measures of Morisky's Medication Adherence Scale 8 (r = -0.450, P < 0.01). All correlations between items and global scores ranged from 0.403 to 0.638. Internal consistency reliability and test-retest reliability were found to be acceptable, as indicated by a Cronbach's α of 0.824 and an intraclass correlation coefficient of 0.846, respectively. CONCLUSIONS: The Mandarin TBQ had acceptable validity and reliability. The use of TBQ in the assessment of treatment burden of stroke survivor may benefit health resources allocation and provide tailor therapeutic interventions to construct minimally disruptive care.

18.
Nano Lett ; 21(4): 1778-1784, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33555892

RESUMO

The effect of nanoporous confinement on the glass transition temperature (Tg) strongly depends on the type of porous media. Here, we study the molecular origins of this effect in a molecular glass, N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD), highly confined in concave and convex geometries. When confined in controlled pore glass (CPG) with convex pores, TPD's vibrational spectra remained unchanged and two Tg's were observed, consistent with previous studies. In contrast, when confined in silica nanoparticle packings with concave pores, the vibrational peaks were shifted due to more planar conformations and Tg increased, as the pore size was decreased. The strong Tg increases in concave pores indicate significantly slower relaxation dynamics compared to CPG. Given TPD's weak interaction with silica, these effects are entropic in nature and are due to conformational changes at molecular level. The results highlight the role of intramolecular degrees of freedom in the glass transition, which have not been extensively explored.

19.
Oncologist ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33543577

RESUMO

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

20.
Comput Biol Chem ; 92: 107453, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33636636

RESUMO

BACKGROUND: It is estimated that there are 338,000 new renal-cell carcinoma releases every year in the world. Renal cell carcinoma (RCC) is a heterogeneous tumor, of which more than 70% is clear cell renal cell carcinoma (ccRCC). It is estimated that about 30% of new renal-cell carcinoma patients have metastases at the time of diagnosis. However, the pathogenesis of renal clear cell carcinoma has not been elucidated. Therefore, it is necessary to further study the pathogenesis of ccRCC. METHODS: Two expression profiling datasets (GSE68417, GSE71963) were downloaded from the GEO database. Differentially expressed genes (DEGs) between ccRCC and normal tissue samples were identified by GEO2R. Functional enrichment analysis was made by the DAVID tool. Protein-protein interaction (PPI) network was constructed. The hub genes were excavated. The clustering analysis of expression level of hub genes was performed by UCSC (University of California Santa Cruz) Xena database. The hub gene on overall survival rate (OS) in patients with ccRCC was performed by Kaplan-Meier Plotter. Finally, we used the ccRCC renal tissue samples to verify the hub genes. RESULTS: 1182 common DEGs between the two datasets were identified. The results of GO and KEGG analysis revealed that variations in were predominantly enriched in intracellular signaling cascade, oxidation reduction, intrinsic to membrane, integral to membrane, nucleoside binding, purine nucleoside binding, pathways in cancer, focal adhesion, cell adhesion molecules. 10 hub genes ITGAX, CD86, LY86, TLR2, TYROBP, FCGR2A, FCGR2B, PTPRC, ITGB2, ITGAM were identified. FCGR2B and TYROBP were negatively correlated with the overall survival rate in patients with ccRCC (P < 0.05). RT-qPCR analysis showed that the relative expression levels of CD86, FCGR2A, FCGR2B, TYROBP, LY86, and TLR2 were significantly higher in ccRCC samples, compared with the adjacent renal tissue groups. CONCLUSIONS: In summary, bioinformatics technology could be a useful tool to predict the progression of ccRCC. In addition, there are DEGs between ccRCC tumor tissue and normal renal tissue, and these DEGs might be considered as biomarkers for ccRCC.

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