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1.
Front Cell Dev Biol ; 9: 738709, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722520

RESUMO

Pancreatic cancer is one of the major malignancies and causes of mortality worldwide. E3 ubiquitin-protein ligases transfer activated ubiquitin from ubiquitin-conjugating enzymes to protein substrates and confer substrate specificity in cancer. In this study, we first downloaded data from The Cancer Genome Atlas pancreatic adenocarcinoma dataset, acquired all 27 differentially expressed genes (DEGs), and identified genomic alterations. Then, the prognostic significance of DEGs was analyzed, and eight DEGs (MECOM, CBLC, MARCHF4, RNF166, TRIM46, LONRF3, RNF39, and RNF223) and two clinical parameters (pathological N stage and T stage) exhibited prognostic significance. RNF223 showed independent significance as an unfavorable prognostic marker and was chosen for subsequent analysis. Next, the function of RNF223 in the pancreatic cancer cell lines ASPC-1 and PANC-1 was investigated, and RNF223 silencing promoted pancreatic cancer growth and migration. To explore the potential targets and pathways of RNF223 in pancreatic cancer, quantitative proteomics was applied to analyze differentially expressed proteins, and metabolism-related pathways were primarily enriched. Finally, the reason for the elevated expression of RNF223 was analyzed, and KLF4 was shown to contribute to the increased expression of RNF233. In conclusion, this study comprehensively analyzed the clinical significance of E3 ligases. Functional assays revealed that RNF223 promotes cancer by regulating cell metabolism. Finally, the elevated expression of RNF223 was attributed to KLF4-mediated transcriptional activation. This study broadens our knowledge regarding E3 ubiquitin ligases and signal transduction and provides novel markers and therapeutic targets in pancreatic cancer.

2.
Health Sci Rep ; 4(4): e390, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34722934

RESUMO

Rationale aims and objectives: Hospital-acquired pressure injuries (HAPI) prolong hospital stays and are an important health problem worldwide. The aim of this study was to assess the frequency of and risk factors for intensive care unit (ICU)-acquired pressure injuries (IAPI) on the sacrum in critically ill patients in China. Methods: We performed a multicenter, cross-sectional survey of IAPI on the sacrum in 23 adult ICUs in 19 hospitals in China. Data for 421 critically ill patients were collected on December 13, 2019, and January 13, 2020, including patient characteristics, physiological, and clinical information. Logistic regression was used to analyze the risk factors for IAPI on the sacrum in the ICU. Results: Forty-one patients presented sacrum pressure injuries in the ICU, with a frequency of 9.74%. Risk factors that significantly increased the risk of IAPI on the sacrum were lower body mass index (BMI, odds ratio [OR] = 1.115, confidence interval [CI]: 1.011-1.229, P = .029), chronic obstructive pulmonary disease (COPD, OR = 3.183, CI: 1.261-8.037, P = .014), multiple organ dysfunction syndrome (MODS, OR = 2.670, CI: 1.031-6.903, P = .043), and a lower Braden risk score (OR = 1.409, CI: 1.197-1.659, P < .001). Conclusion: Lower BMI, COPD, MODS, and lower Braden risk score are independent risk factors for sacrum IAPI in China.

3.
Synth Syst Biotechnol ; 6(4): 335-342, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34738044

RESUMO

The versatile photosynthetic α-proteobacterium Rhodobacter sphaeroides, has recently been extensively engineered as a novel microbial cell factory (MCF) to produce pharmaceuticals, nutraceuticals, commodity chemicals and even hydrogen. However, there are no well-characterized high-activity promoters to modulate gene transcription during the engineering of R. sphaeroides. In this study, several native promoters from R. sphaeroides JDW-710 (JDW-710), an industrial strain producing high levels of co-enzyme Q10 (Q10) were selected on the basis of transcriptomic analysis. These candidate promoters were then characterized by using gusA as a reporter gene. Two native promoters, P rsp _ 7571 and P rsp _ 6124 , showed 620% and 800% higher activity, respectively, than the tac promoter, which has previously been used for gene overexpression in R. sphaeroides. In addition, a P rsp _ 7571 -derived synthetic promoter library with strengths ranging from 54% to 3200% of that of the tac promoter, was created on the basis of visualization of red fluorescent protein (RFP) expression in R. sphaeroides. Finally, as a demonstration, the synthetic pathway of Q10 was modulated by the selected promoter T334* in JDW-710; the Q10 yield in shake-flasks increased 28% and the production reached 226 mg/L. These well-characterized promoters should be highly useful in current synthetic biology platforms for refactoring the biosynthetic pathway in R. sphaeroides-derived MCFs.

4.
World J Clin Cases ; 9(28): 8388-8403, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754848

RESUMO

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic is a global threat caused by the severe acute respiratory syndrome coronavirus-2. AIM: To develop and validate a risk stratification tool for the early prediction of intensive care unit (ICU) admission among COVID-19 patients at hospital admission. METHODS: The training cohort included COVID-19 patients admitted to the Wuhan Third Hospital. We selected 13 of 65 baseline laboratory results to assess ICU admission risk, which were used to develop a risk prediction model with the random forest (RF) algorithm. A nomogram for the logistic regression model was built based on six selected variables. The predicted models were carefully calibrated, and the predictive performance was evaluated and compared with two previously published models. RESULTS: There were 681 and 296 patients in the training and validation cohorts, respectively. The patients in the training cohort were older than those in the validation cohort (median age: 63.0 vs 49.0 years, P < 0.001), and the percentages of male gender were similar (49.6% vs 49.3%, P = 0.958). The top predictors selected in the RF model were neutrophil-to-lymphocyte ratio, age, lactate dehydrogenase, C-reactive protein, creatinine, D-dimer, albumin, procalcitonin, glucose, platelet, total bilirubin, lactate and creatine kinase. The accuracy, sensitivity and specificity for the RF model were 91%, 88% and 93%, respectively, higher than those for the logistic regression model. The area under the receiver operating characteristic curve of our model was much better than those of two other published methods (0.90 vs 0.82 and 0.75). Model A underestimated risk of ICU admission in patients with a predicted risk less than 30%, whereas the RF risk score demonstrated excellent ability to categorize patients into different risk strata. Our predictive model provided a larger standardized net benefit across the major high-risk range compared with model A. CONCLUSION: Our model can identify ICU admission risk in COVID-19 patients at admission, who can then receive prompt care, thus improving medical resource allocation.

6.
Ann Palliat Med ; 10(10): 10768-10778, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763438

RESUMO

BACKGROUND: Left ventricular (LV) hypertrophy predicts worse cardiac outcomes. Blood pressure lowering is associated with the reduction of LV hypertrophy. This study evaluated the effect of a calcium channel blocker, amlodipine, on LV hypertrophy in patients with hypertension. METHODS: Studies were identified by conducting a literature survey in electronic databases, and study selection was carried out according to precise eligibility criteria. Meta-analyses of mean change between the follow-up and baseline values of systolic/diastolic blood pressure (SBP/DBP) and LV hypertrophy indices were performed. Meta-regression analyses were performed to examine the factors affecting changes in these indices. RESULTS: Twenty-three studies [involving 737 patients; age 56.4 years, 95% confidence interval (CI): 53.5-59.2; females 34%, 95% CI: 25-44%; body mass index 26.4 kg/m2, 95% CI: 24.6-28.1] were included. Amlodipine treatment led to a significant reduction in SBP (-24.9 mmHg; 95% CI: -28.3 to -21.6; P<0.0001) and DBP (-14.8; 95% CI: -16.4 to -13.3; P<0.0001), without affecting the heart rate. Amlodipine treatment also significantly reduced the LV mass index. The mean difference (MD) between the follow-up and baseline LV mass index was -12.9; 95% CI: -15.4 to -10.4 (P<0.001). This decrease in LV mass index was positively associated with the follow-up duration [meta-regression coefficient (MC): 0.392; 95% CI: 0.050-0.733; P=0.026] and baseline LV mass index (MC: 0.139; 95% CI: 0.007-0.271; P=0.040). Amlodipine treatment significantly reduced the LV posterior wall thickness, which was also positively associated with the follow-up duration. There was no significant decrease in the LV end-diastolic diameter following amlodipine treatment. DISCUSSION: Amlodipine treatment in patients with hypertension significantly reduced the LV mass index and LV posterior wall thickness, without notably affecting the LV end-diastolic diameter. Since many of the included studies were non-randomized, open-label, or lacking appropriate comparability, we therefore performed pooled analyses of the changes from baseline, and a comparative account could not be carried out.


Assuntos
Anlodipino , Hipertensão , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Pessoa de Meia-Idade
7.
Artigo em Inglês | MEDLINE | ID: mdl-34757705

RESUMO

OBJECTIVES: Vitamin D promotes both lipolysis and lipogenesis, and some pediatric studies showed inconsistent associations between vitamin D and metabolic syndrome (MetS). This cross-sectional study aimed to examine the association between vitamin D levels and MetS components among metropolitan adolescents. METHODS: A total of 4,149 adolescents aged 10-18 years were recruited from 23 metropolises in China. The MetS conditions were assessed according to the International Diabetes Federation consensus definition, and the serum 25-hydroxy vitamin D (25(OH)D) concentrations were analyzed. The association between MetS components and serum 25(OH)D levels was analyzed by the logistic regression model. Restricted cubic spline was applied to the model nonlinear association. RESULTS: Prevalence of vitamin D deficiency was 74.9%, and 41.2% of study participants had at least one MetS component. After adjustment, the significant trend for a lower waist-to-height ratio was not observed in study participants with higher serum 25(OH)D quartile (p=0.57), but a significant nonlinear association between abdominal obesity and serum 25(OH)D levels was found (p=0.04): the highest risk of abdominal obesity occurred at 14.1 ng/mL of serum 25(OH)D. The association of serum 25(OH)D was significantly inverse with MetS (OR: 0.95; 95% CI: 0.92-0.98), but not with raised triglycerides (OR: 0.99; 95% CI: 0.96-1.01), raised blood pressure (OR: 0.99; 95% CI: 0.97-1.01) and impaired fasting glycemia (OR: 1.03; 95% CI: 1.01-1.04). CONCLUSIONS: The net effect of vitamin D on lipid metabolism may be concentration-dependent, and the actual effect of vitamin D on MetS process may be complex among metropolitan adolescents, though serum 25(OH)D is inversely associated with MetS.

8.
Int J Oncol ; 59(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34751413

RESUMO

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, on p. 1969, two pairs of panels shown for the DU145 data appeared to contain overlaps, such that they may have been derived from the same original source (specifically, relating to the shCon and the shSMC1A experiments). The authors have referred back to their original data, and realize that inadvertent errors were made during the assembly of these figures. The corrected version of Fig. 5, showing discrete representative images for the shCon and the shSMC1A experiments with the DU145 cell line, is shown on the next page. All the authors agree to this corrigendum. Note that the revisions made to this figure do not adversely affect the results reported in the paper, or the conclusions stated therein. The authors regret that Fig. 5 was not presented in its correct form in their paper, thank the Editor of International Journal of Oncology for granting them the opportunity to publish this corrigendum, and offer their apologies to the Editor and to the readers of the Journal. [the original article was published in International Journal of Oncology 49: 1963-1972, 2016; DOI: 10.3892/ijo.2016.3697].

9.
BMC Pulm Med ; 21(1): 359, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753450

RESUMO

BACKGROUND: Small plateau (SP) on the flow-volume curve was found in parts of patients with suspected asthma or upper airway abnormalities, but it lacks clear scientific proof. Therefore, we aimed to characterize its clinical features. METHODS: We involved patients by reviewing the bronchoprovocation test (BPT) and bronchodilator test (BDT) completed between October 2017 and October 2020 to assess the characteristics of the sign. Patients who underwent laryngoscopy were assigned to perform spirometry to analyze the relationship of the sign and upper airway abnormalities. SP-Network was developed to recognition of the sign using flow-volume curves. RESULTS: Of 13,661 BPTs and 8,168 BDTs completed, we labeled 2,123 (15.5%) and 219 (2.7%) patients with the sign, respectively. Among them, there were 1,782 (83.9%) with the negative-BPT and 194 (88.6%) with the negative-BDT. Patients with SP sign had higher median FVC and FEV1% predicted (both P < .0001). Of 48 patients (16 with and 32 without the sign) who performed laryngoscopy and spirometry, the rate of laryngoscopy-diagnosis upper airway abnormalities in patients with the sign (63%) was higher than those without the sign (31%) (P = 0.038). SP-Network achieved an accuracy of 95.2% in the task of automatic recognition of the sign. CONCLUSIONS: SP sign is featured on the flow-volume curve and recognized by the SP-Network model. Patients with the sign are less likely to have airway hyperresponsiveness, automatic visualizing of this sign is helpful for primary care centers where BPT cannot available.

10.
Asian J Androl ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34782549

RESUMO

To analyze the performance of the Prostate Health Index (phi) and its derivatives for predicting Gleason score (GS) upgrading between prostate biopsy and radical prostatectomy (RP) in the Chinese population, an observational, prospective RP cohort consisting of 351 patients from two medical centers was established from January 2017 to September 2020. Pathological reclassification was determined by the Gleason Grade Group (GG). The area under the receiver operating characteristic curve (AUC) and logistic regression (LR) models were used to evaluate the predictive performance of predictors. In clinically low-risk patients with biopsy GG ≤ 2, phi (odds ratio [OR] = 1.80, 95% confidence interval [95% CI]: 1.14-2.82, P = 0.01) and its derivative phi density (PHID; OR = 2.34, 95% CI: 1.30-4.20, P = 0.005) were significantly associated with upgrading to GG ≥ 3 after RP, and the results were confirmed by multivariable analysis. Similar results were observed in patients with biopsy GG of 1 for the prediction of upgrading to RP GG ≥ 2. Compared to the base model (AUC = 0.59), addition of the phi or PHID could provide additional predictive value for GS upgrading in low-risk patients (AUC = 0.69 and 0.71, respectively, both P < 0.05). In conclusion, phi and PHID could predict GS upgrading after RP in clinically low-risk patients.

11.
Genes (Basel) ; 12(11)2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34828290

RESUMO

Plasmid-mediated fosfomycin determinants is a global public health concern due to the increasing dissemination of fosfomycin resistance and limited clinical treatment options. Information about the fosfomycin resistant and molecular genetic among Enterococcus spp. is still lacking. In this study, we found the first plasmid-medieted fosB in Enterococcus faecalis from pigs, and all the fosfomycin resistant Enterococcus spp. (FRE) isolates were multi-drug resistant. S1-PFGE, Southern blot and conjugation experiments indicated that the fosB gene located on ~54.7 kb transferable plasmids. Relative competition assay confirmed that the fosB-carrying plasmid impaired fitness in recipient E. faecalis JH2-2. Illumina and the MinION sequencing data revealed that both E. faecalis ES-1 and ES-2 isolates belonged to novel ST (ST964), and had 71 SNPs difference. WGS showed that the genetic environments of fosB were diverse among different species, and the linezolid resistance gene optrA was found in the fosB-carrying strains. To summarize, for the first time, we reported plasmid-mediated fosB in E. faecalis from pigs. And, the co-occurrence of fosB and optrA pose a serious threat to public health.

12.
Front Pharmacol ; 12: 658197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776939

RESUMO

Background: Cancer is the second leading cause of death globally. However, most of the new anti-cancer agents screened by traditional drug screening methods fail in the clinic because of lack of efficacy. Choosing an appropriate in vitro tumor model is crucial for preclinical drug screening. In this study, we screened anti-hepatocarcinoma (HCC) drugs using a novel spheroid cell culture device. Methods: Four HCC cell lines were three-dimensionally (3D) cultured to screen 19 small molecular agents. 3D-cultured primary HCC cells and a tumor-bearing mouse model were used to verify the candidate anti-hepatocarcinoma agent. Cell function experiments and western blotting were conducted to explore the anti-hepatocarcinoma mechanism of the candidate agent. Results: We found that CUDC-907 can serve as a potent anti-hepatocarcinoma agent. The study data show that CUDC-907 (fimepinostat), a novel dual acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), has potent inhibitory effects on HCC cell lines and primary HCC cells in vitro, Animal studies have shown that CUDC-907 can also suppress HCC cells in vivo. Furthermore, we found that CUDC-907 inhibits the PI3K/AKT/mTOR pathway and downregulates the expression of c-Myc, leading to the suppression of HCC cells. Conclusion: Our results suggest that CUDC-907 can be a candidate anti-HCC drug, and the 3D in vitro drug screening method based on our novel spheroid culture device is promising for future drug screening efforts.

13.
Biomed Res Int ; 2021: 6673125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595239

RESUMO

Background: Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. Methods: Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. Results: The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. Conclusions: These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.

14.
Prostaglandins Other Lipid Mediat ; 157: 106595, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34597782

RESUMO

Although epoxyeicosatrienoic acids (EETs) have multiple protective effects against different diseases, whether they can improve the pathogenesis of lipopolysaccharide (LPS)-induced septic cardiac dysfunction remains unknown. We investigated the effects of EETs on the LPS-induced inflammatory response in myocardial dysfunction mice and H9c2 cardiac myocytes. Cardiac-specific CYP2J2 transgenic mice (Tr) showed improved cardiac function and reduced inflammation response after administration with LPS, while the protective effects were not observed in A2A adenosine receptor (A2AR/ADORA2A)-deficient mice (knockout/KO). In vitro, EETs prevented LPS-induced inflammation and apoptosis in the cardiomyocytes via A2AR activation. Moreover, ZM241385 (A2AR inhibitor) attenuated the cardioprotective properties of EETs. Further investigation demonstrated that A2AR signal pathway activation partly regulated phosphatidylinositol 3-kinase (PI3K) and peroxisome proliferator-activated receptor-γ (PPARγ) expression. This is the first report on EETs exerting cardioprotective effects against LPS-induced cardiomyocyte injury via A2AR activation.

15.
Natl Sci Rev ; 8(9): nwaa234, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34691725

RESUMO

Photosynthesis in nature uses the Mn4CaO5 cluster as the oxygen-evolving center to catalyze the water oxidation efficiently in photosystem II. Herein, we demonstrate bio-inspired heterometallic LnCo3 (Ln = Nd, Eu and Ce) clusters, which can be viewed as synthetic analogs of the CaMn4O5 cluster. Anchoring LnCo3 on phosphorus-doped graphitic carbon nitrides (PCN) shows efficient overall water splitting without any sacrificial reagents. The NdCo3/PCN-c photocatalyst exhibits excellent water splitting activity and a quantum efficiency of 2.0% at 350 nm. Ultrafast transient absorption spectroscopy revealed the transfer of a photoexcited electron and hole into the PCN and LnCo3 for hydrogen and oxygen evolution reactions, respectively. A density functional theory (DFT) calculation showed the cooperative water activation on lanthanide and O-O bond formation on transition metal for water oxidation. This work not only prepares a synthetic model of a bio-inspired oxygen-evolving center but also provides an effective strategy to realize light-driven overall water splitting.

16.
ACS Omega ; 6(39): 25742-25748, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34632230

RESUMO

Using apricot shell lignin as a raw material, the effects of torrefaction temperatures (160, 200, 240, and 280 °C) on the properties of torrefied products were studied, and the catalytic pyrolysis experiments of the torrefied lignin under the HZSM-5 catalyst were carried out. The results showed that the oxygen content in lignin was greatly reduced and the higher heating values (HHV) gradually increased, the absorption peak of oxygen-containing functional groups gradually became weaker, and the content of the ß-O-4 bond gradually decreased. At 280 °C, the C/O ratio reaches the maximum value of 2.17, and the calorific value increases to 24.22 MJ/kg. The removed oxygen element is converted into oxygen-containing components in the gas (mainly CO2 and H2O) and liquid products (mainly guaiacol phenol). After catalytic pyrolysis of torrefied lignin, it was found that with the increase of torrefaction temperature, the relative content of aromatics increased first and then decreased slightly; the aromatics reached the maximum value of 60.63% at 240 °C; acids decreased significantly; ketones, aldehydes, and furans changed little; and torrefaction played a positive role in the conversion of lignin to aromatics.

17.
ACS Omega ; 6(39): 25772-25781, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34632233

RESUMO

The molecular structure model of lignite was constructed, and the dissociation and removal mechanism of different C-O bonds and oxygen-containing functional groups was investigated using density functional theory (DFT) calculations. First, the bond order and bond dissociation enthalpy (BDE) were analyzed to predict the strength of different chemical bonds, and differences in the BDE and bond order were related to the difference in the fragment structure and electronic effects. The first group to break during hydrothermal carbonization (HTC) is the methyl of Ph(CO)O-CH3, followed by the C-O of CH3-OC(O)OH; the hydroxyl in Ph-OH is the most thermally stable group, followed by the hydroxyl in CH3OC(O)-OH. In addition, the orbital localization analysis has also been carried out. All three chemical bonds of Ph(CO)OCH3 show the characteristics of σ bond, while Ph(C=O)OCH3 and Ph(CO)-OCH3 with the Mayer bond order (MBO) greater than 1 also contains certain π bond characteristics. The lignite van der Waals (vdW) surface electrostatic potential (ESP) was constructed and visualized, and the results showed that the oxygen-containing functional groups mainly contributed to the area with a large absolute ESP. Finally, weak interactions between water molecules and lignite at different sites were described by independent gradient model (IGM) analysis. Models A, B, and E formed weak interactions with the hydrogen bond as the main force; model E showed the weakest hydrogen bond, while model C showed van der Waals interaction as the dominant force. In addition, some steric effect was also observed in model D.

18.
Cells ; 10(10)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34685501

RESUMO

Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.

19.
Life Sci ; 287: 120056, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34687756

RESUMO

AIMS: Discs large-associated protein 5 (DLGAP5), a kinetochore fibers-binding protein, functions as a oncoprotein in many cancers. However, its expression patterns in pan-cancer including clear cell renal cell carcinoma (ccRCC) are not analyzed. Herein, we aimed to evaluate its expression in more common cancers, especially in ccRCC. MAIN METHODS: Data from Genotype-Tissue Expression, The Cancer Genome Atlas, and Tumor Immune Estimation Resource were used to analyze the DLGAP5 expression in normal tissues, cancer cell lines, and cancer tissues, as well as the immune infiltration levels. The analysis results were verified with ccRCC cell lines via RNAi, western blotting, and the cytological analysis. KEY FINDINGS: Low DLGAP5 expression in 31 types of normal tissues, the upregulation in 21 cancer cell lines, and the significant elevated expression in 26 types of cancers, were found, Surprisingly, kidney cancer including ccRCC, DLGAP5 exhibited a slightly elevated but statistically significant expression among 26 types of cancers. In addition, elevated DLGAP5 expression was significantly positive correlated with immune infiltration level in ccRCC. The survival probability of some cancers including kidney cancer, clinical TNM stage of ccRCC patients were significantly related to upregulated DLGAP5 expression. The experiments results showed DLGAP5 upregulation in ccRCC tissues and the cell lines, its knockdown inhibited the cells viability and proliferation, and compromised the cells migration and invasion. SIGNIFICANCE: Elevated DLGAP5 expression occurred in common cancers. However, its slightly upregulated expression is related with ccRCC progression, it is therefore a prognostic risk factor for ccRCC, but not an independent factor.

20.
Appl Microbiol Biotechnol ; 105(23): 8675-8688, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34716786

RESUMO

A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.Key points• An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.• PGL protected PC12 nerve cells from the toxicity of corticosterone.• PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Reishi , Agaricus , Animais , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Modelos Animais de Doenças , Camundongos , Córtex Pré-Frontal/metabolismo , Ratos , Esporos Fúngicos/metabolismo , Estresse Psicológico , Sacarose , Regulação para Cima
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