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1.
Diabetes Res Clin Pract ; : 108842, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33933497

RESUMO

AIM: To study the association between diabetes and the prevalence of and risk factors for polypharmacy among adults aged 50 and older in England. METHODS: A cross-sectional study (2012-2013) of the English Longitudinal Study of Ageing. Polypharmacy was defined as taking 5-9 long-term medications a day and heightened polypharmacy as 10 or more. Diabetes included diagnosed and undiagnosed cases (glycated haemoglobin ≥ 6.5% (48 mmol/mol)). RESULTS: Of 7729 participants, 1100 people had diabetes and showed higher prevalence rates of polypharmacy (41.1% vs 14.8%) and heightened polypharmacy (5.8% vs 1.7%) than those without diabetes, even when antihyperglycemic medications were excluded. Risk factors for polypharmacy also differed according to diabetes status. Among people with diabetes, risk factors for polypharmacy and heightened polypharmacy were having more long-term conditions (relative risk ratio (RRR) =1.86; 3.51) and being obese (RRR=1.68; 3.68), while females were less likely to show polypharmacy (RRR=0.51) and heightened polypharmacy (RRR=0.51) than males. Older age (RRR=1.04) was only related to polypharmacy among people without diabetes. CONCLUSIONS: Adults with diabetes had higher prevalence rates of polypharmacy and heightened polypharmacy than those without diabetes, regardless of including antihyperglycemic drugs. Early detection of polypharmacy among older people with diabetes needs to focus on co-morbidities and obesity.

2.
Nucleic Acids Res ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33877329

RESUMO

DNA cytosine methylation in mammals modulates gene expression and chromatin accessibility. It also impacts mutation rates, via spontaneous oxidative deamination of 5-methylcytosine (5mC) to thymine. In most cases the resulting T:G mismatches are repaired, following T excision by one of the thymine DNA glycosylases, TDG or MBD4. We found that C-to-T mutations are enriched in the binding sites of CCAAT/enhancer binding proteins (CEBP). Within a CEBP site, the presence of a T:G mismatch increased CEBPß binding affinity by a factor of >60 relative to the normal C:G base pair. This enhanced binding to a mismatch inhibits its repair by both TDG and MBD4 in vitro. Furthermore, repair of the deamination product of unmethylated cytosine, which yields a U:G DNA mismatch that is normally repaired via uracil DNA glycosylase, is also inhibited by CEBPß binding. Passage of a replication fork over either a T:G or U:G mismatch, before repair can occur, results in a C-to-T mutation in one of the daughter duplexes. Our study thus provides a plausible mechanism for accumulation of C-to-T human somatic mutations.

3.
Acta Diabetol ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890177

RESUMO

AIMS: Chronic inflammation of autoimmune diseases, including type 1 diabetes (T1D), is mainly mediated by memory T(Tm) cells, predominantly effector memory T (Tem) cells. The roles of the programmed death-1 (PD-1) receptor on lymphocytes have been well studied in tumor and other infection models. However, little is known about the relationship between the expression of PD-1 on CD8+ Tem cells and the pathogenesis of T1D. METHODS: A total of 52 patients diagnosed with T1D and 39 gender-, age-, and ethnically matched health control individuals were enrolled in this study. Peripheral blood mononuclear cells from these individuals were isolated and analyzed by flow cytometry. We evaluated the frequencies of PD-1+ CD8+ memory T cell subsets from patients' peripheral blood with T1D and the spleen cells of nonobese diabetic (NOD) mice in the present study. We also investigated the effects of blocking PD-1/PD-L1 pathway on islet's inflammation in NOD mice. RESULTS: Frequencies of PD-1+ CD8+ Tem cells were decreased significantly in PBMC of patients with T1D (40.73 ± 12.72 vs 47.43 ± 15.56, *p < 0.05). The frequencies of PD-1+ CD8+ Tem cells were decreased in patients with T1D who were positive for two or more autoantibodies compared with the patients with one autoantibody (13.46% vs 46.95 ± 12.72%, *p < 0.05). Meanwhile, the frequencies of PD-1+ CD8+ central memory T (Tcm) cells were also significantly decreased in patients with two or more autoantibodies compared with other groups (≥ 2AAb vs HC 33.1 ± 8.92% vs 43.71 ± 11.78%, *p < 0.05; ≥ 2AAb vs AAb-33.1 ± 8.92% vs 41.65 ± 11.2%, *p < 0.05; ≥ 2AAb vs 1AAb 33.1 ± 8.92% vs 48.09 ± 10.58%, ***p < 0.001). The frequencies of PD-1+CD8+ Tem cells were positively correlated with fasting serum C-peptide levels (r = 0.4308, *p < 0.05) and C-peptide levels 2 h after meal in T1D patients (r = 0.5723, **p < 0.01). The frequencies of PD-1+CD8+ Tcm cells were only negatively correlated with the levels of HbA1c (r = - 0.2992, *p < 0.05). Similarly, the frequencies of PD-1+CD8+ Tem were significantly decreased in intervention group (anti-mouse PD-1 mAb) compared with the control group (14.22 ± 6.455% vs 27.69 ± 9.837%, *p < 0.05). Pathologically, CD8, PD-1 and PD-L1 were strongly expressed in the islets of diabetic mice after PD-1 blockade. CONCLUSIONS: It is the first report of the expression of PD-1 on CD8+ Tem cells in T1D in the present study. Our observations suggest that the PD-1/PD-L1 signal pathway on CD8+ Tem cells of T1D subjects might identify a new pathway for delaying the occurrence and development by inhibiting autoimmunity.

4.
Int J Mol Sci ; 22(8)2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923724

RESUMO

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Children aged <5 years are the most affected by CA16 HFMD globally. Although clinical symptoms of CA16 infections are usually mild, severe complications, such as aseptic meningitis or even death, have been recorded. Currently, no vaccine or antiviral therapy for CA16 infection exists. Single-chain variable fragment (scFv) antibodies significantly inhibit viral infection and could be a potential treatment for controlling the infection. In this study, scFv phage display libraries were constructed from splenocytes of a laying hen immunized with CA16-infected lysate. The pComb3X vector containing the scFv genes was introduced into ER2738 Escherichia coli and rescued by helper phages to express scFv molecules. After screening with five cycles of bio-panning, an effective scFv antibody showing favorable binding activity to proteins in CA16-infected lysate on ELISA plates was selected. Importantly, the selected scFv clone showed a neutralizing capability against the CA16 virus and cross-reacted with viral proteins in EV71-infected lysate. Intriguingly, polyclonal IgY antibody not only showed binding specificity against proteins in CA16-infected lysate but also showed significant neutralization activities. Nevertheless, IgY-binding protein did not cross-react with proteins in EV71-infected lysate. These results suggest that the IgY- and scFv-binding protein antibodies provide protection against CA16 viral infection in in vitro assays and may be potential candidates for treating CA16 infection in vulnerable young children.

6.
Sci Rep ; 11(1): 7573, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33828187

RESUMO

In quantitative PCR research, appropriate reference genes are key to determining accurate mRNA expression levels. In order to screen the reference genes suitable for detecting gene expression in tissues of the reproductive axis, a total of 420 (males and females = 1:5) 3-year-old Magang geese were selected and subjected to light treatment. The hypothalamus, pituitary and testicular tissues were subsequently collected at different stages. Ten genes including HPRT1, GAPDH, ACTB, LDHA, SDHA, B2M, TUBB4, TFRC, RPS2 and RPL4 were selected as candidate reference genes. The expression of these genes in goose reproductive axis tissues was detected by real-time fluorescent quantitative PCR. The ΔCT, geNorm, NormFinder and BestKeeper algorithms were applied to sort gene expression according to stability. The results showed that ACTB and TUBB4 were the most suitable reference genes for the hypothalamic tissue of Magang goose in the three breeding stages; HPRT1 and RPL4 for pituitary tissue; and HPRT1 and LDHA for testicular tissue. For all three reproductive axis tissues, ACTB was the most suitable reference gene, whereas the least stable reference gene was GAPDH. Altogether, these results can provide references for tissue expression studies in geese under light treatment.

7.
Pharm Biol ; 59(1): 504-512, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33905670

RESUMO

CONTEXT: Gynura bicolour (Roxb. and Willd.) DC (Asteraceae) leaf is a common vegetable. Ethanol extracts of fresh G. bicolour leaves (GBEE) have several physiological effects, but studies on atherosclerosis are limited. OBJECTIVE: We investigated the oxidant scavenging ability and vascular adhesion molecule expression of these extracts. MATERIALS AND METHODS: The antioxidant effects of 0.05-0.4 mg/mL GBEE were analyzed in vitro. Intracellular antioxidant capacity and adhesion molecule levels were detected in EA.hy926 cells pre-treated with 10-100 µg/mL GBEE for 8 h, then TNF-α for 3 h. The antioxidant capacity of red blood cells and the adhesion molecule levels in the thoracic aorta were detected in high-fat diet (HFD)-fed Sprague-Dawley rats treated with GBEE for 12 weeks. RESULTS: The in vitro EC50 values of GBEE based on its DPPH radical-scavenging ability, reducing power, and ferrous ion-chelating ability were 0.20, 3.21 and 0.49 mg/mL, respectively. In TNF-α-treated EA.hy926 cells, the thiobarbituric acid-reactive substance levels were decreased after 10, 50, or 100 µg/mL GBEE treatments (IC50: 19.1 mg/mL). When HFD-fed rats were co-treated with GBEE, the GBEE-H group exhibited 25% higher glutathione levels than the HFD group (p < 0.05). E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion protein-1 levels were decreased in TNF-α-treated EA.hy926 cells after GBEE treatment (by approximately 11-73%; p < 0.05), and the above three adhesion molecules levels were decreased in HFD-fed rats with combined GBEE treatment (by approximately 30-77%; p < 0.05). CONCLUSIONS: GBEE can protect the vascular endothelium by reducing adhesion molecule expression and regulating antioxidants. It may have the potential to prevent atherosclerosis.

8.
Nutrients ; 13(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33803057

RESUMO

Danshensu, a traditional herb-based active component (Salvia miltiorrhiza Bunge), has garnered attention, due to its safety, nutritional value, and antioxidant effects, along with cardiovascular-protective and neuroprotective abilities; however, its effect on the retinal tissues and functional vision has not been fully studied. The objective of this study was to analyze the protective effect of danshensu on retinal tissues and functional vision in vivo in a mouse model of light-induced retinal degeneration. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in visual acuity and visual contrast sensitivity function (VCSF), whereas the retina tissue exhibited severe Müller cell gliosis. Although danshensu treatment did not particularly reduce light-evoked damage to the photoreceptors, it significantly prevented Müller cell gliosis. Danshensu exerted protective effects against light-evoked deterioration on low spatial frequency-based VCSF as determined by the behavioral optomotor reflex method. Additionally, the protective effect of danshensu on VCSF can be reversed and blocked by the injection of a dopamine D1 receptor antagonist (SCH 23390). This study demonstrated that the major functional vision promotional effect of danshensu in vivo was through the dopamine D1 receptors enhancement pathway, rather than the structural protection of the retinas.

9.
Molecules ; 26(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807346

RESUMO

Endometrial cancer is the most common malignant tumors of gynecologic neoplasms in Western society. In recent years, the incidence of endometrial cancer has increased, and it has become the third most common female gynecological cancer (after ovarian and cervical cancer) in Taiwan. Adlay (Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been demonstrated to have bioactive polyphenols, flavonoids, phytosterols, and essential nutrients for health benefits, including anticancer effects in humans. However, little is known about the effect of adlay seeds on endometrial cancer. Our study aimed to investigate the potential growth inhibitory effects of several adlay seed fractions, including ethyl acetate (ATE-EA) and its bioactive constituents, separately on endometrial cancer cells-HEC-1A (phosphatase and tensin homolog-positive) and RL95-2 (phosphatase and tensin homolog-negative)-and identify related active ingredients. In addition, the potential active fractions and the phytochemical compounds were elucidated. The results demonstrate superior activity of ATE-EA with significant in vitro cell proliferation inhibitory capacity, particularly its C.D.E.F-subfraction. Moreover, HPLC- and GC/FID-based quantification of ATE-EA subfractions showed that phenolic compounds (caffeic acid, protocatechuic acid, and p-hydroxybenzaldehyde), flavonoids, steroids, and fatty acid compounds exert anti-proliferative effects in the cell model. Finally, it was shown that cell growth and cell cycle arrest most significantly occurred in the in G1 or G2/M phase under ATE-EA treatment. Collectively, our results demonstrate an antiproliferative effect of ATE-EA on endometrial cancer cells that suggest a positive health outcome for women from consumption of these compounds.

10.
BMC Health Serv Res ; 21(1): 288, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789627

RESUMO

BACKGROUND: Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the stroke care systems have been seriously affected because of social restrictions and other reasons. As the pandemic continues to spread globally, it is of great significance to understand how COVID-19 affects the stroke care systems in mainland China. METHODS: We retrospectively studied the real-world data of one comprehensive stroke center in mainland China from January to February 2020 and compared it with the data collected during the same period in 2019. We analyzed DTN time, onset-to-door time, severity, effects after treatment, the hospital length of stays, costs of hospitalization, etc., and the correlation between medical burden and prognosis of acute ischemic stroke (AIS) patients. RESULTS: The COVID-19 pandemic was most severe in mainland China in January and February 2020. During the pandemic, there were no differences in pre-hospital or in-hospital workflow metrics (all p>0.05), while the degree of neurological deficit on admission and at discharge, the effects after treatment, and the long-term prognosis were all worse (all p<0.05). The severity and prognosis of AIS patients were positively correlated with the hospital length of stays and total costs of hospitalization (all p<0.05). CONCLUSIONS: COVID-19 pandemic is threatening the stroke care systems. Measures must be taken to minimize the collateral damage caused by COVID-19.

11.
ACS Nano ; 15(3): 5428-5438, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33689300

RESUMO

NIR-II (1000-1700 nm) fluorescence imaging is continually attracting strong research interest. However, current NIR-II imaging materials are limited to small molecules with fast blood clearance and inorganic nanomaterials and organic conjugated polymers of poor biodegradability and low biocompatibility. Here, we report a highly biodegradable polyester carrying tandem NIR-II fluorophores as a promising alternative. The polymer encapsulated a platinum intercalator (56MESS, (5,6-dimethyl-1,10-phenanthroline) (1S,2S-diaminocyclohexane) platinum(II)) and was conjugated with both a cell-targeting RGD peptide and a caspase-3 cleavable peptide probe to form nanoparticles for simultaneous NIR-II and apoptosis imaging. In vitro, the nanoparticles were approximately 4-1000- and 1.5-10-fold more potent than cisplatin and 56MESS, respectively. Moreover, in vivo, they significantly inhibited tumor growth on a multidrug-resistant patient-derived mouse model (PDXMDR). Finally, through label-free laser desorption-ionization mass spectrometry imaging (MALDI-MSI), in situ 56MESS release in the deeper tumors was observed. This work highlighted the use of biodegradable NIR-II polymers for monitoring drugs in vivo and therapeutic effect feedback in real-time.

12.
World J Surg Oncol ; 19(1): 73, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33714262

RESUMO

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) is rising every year; however, the mode of operation for Siewert II AEG is still controversial. Accumulating evidence has shown that transabdominal surgery is better than transthoracic surgery for Siewert II AEG with esophageal invasion < 3 cm. In patients with obesity, a large tumor size, and high transection of the esophagus, the transabdominal esophageal hiatus approach for lower mediastinal lymph node dissection and posterior mediastinal anastomosis is difficult. Thus, total laparoscopic radical resection of Siewert II AEG is carried out through the left diaphragm and left chest auxiliary hole for the optimal surgical field of vision and space. In this prospective study, we assessed the feasibility of carrying out the procedure abdominally through the left diaphragm and auxiliary hole. METHODS: Ten patients with Siewert II AEG were recruited between April and June 2019. Siewert II AEG was treated by total laparoscopy through the left diaphragm and left chest auxiliary hole. Clinicopathological features, surgical data, and adverse events were collected and analyzed in this prospective study. RESULTS: The average duration of the operation was 348 ± 37.52 min, lower mediastinal dissection took 20.6 min, the OrVil anastomosis time was 29.8 min, the time necessary to suture the seromuscular layer through the left thoracic auxiliary hole was 11 min, the safety margin was 3.2 cm, and the total number of lymph nodes dissected was 40.6. The number of lower mediastinal lymph nodes dissected was 6.2. The rate of lymph node metastasis in the N110 group was 9 ± 12.45%, and the average intraoperative blood loss was 170 ± 57.47 mL. No anastomotic leakage or anastomotic stricture occurred after the operation. The time of intestinal function recovery was 2 days, and the first time of enteral nutrition through a jejunal nutrition tube was 2.4 days. No tumor recurrence was found in 10 patients at 1 year postoperatively. CONCLUSION: Total laparoscopic radical resection through the left diaphragm and left thoracic auxiliary hole for Siewert II AEG patients is feasible and safe. Thus, it may be a good surgical alternative for patients with esophageal tumors invading less than 3 cm. TRIAL REGISTRATION: ChiCTR, ChiCTR2000034286. Registered 8 July 2020, http://www.chictr.org.cn/showproj.aspx?proj=55866 .

13.
Sci Total Environ ; 779: 146197, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33744586

RESUMO

With increasingly serious environmental pollution problems, research has focused on identifying functional genes within plants that can help ensure food security and soil governance. In particular, plants seem to have been able to evolve specific functional genes to respond to environmental changes by losing partial gene functions, thereby representing a novel adaptation mechanism. Herein, a new category of functional genes was identified and investigated, providing new directions for understanding heavy metal detoxification mechanisms. Interestingly, this category of proteins appears to exhibit specific complexing functions for heavy metals. Further, a new approach was established to evaluate ATP-binding cassette (ABC) transporter family functions using microRNA targeted inhibition. Moreover, mutant and functional genes were identified for future research targets. Expression profiling under five heavy metal stress treatments provided an important framework to further study defense responses of plants to metal exposure. In conclusion, the new insights identified here provide a theoretical basis and reference to better understand the mechanisms of heavy metal tolerance in potato plants. Further, these new data provide additional directions and foundations for mining gene resources for heavy metal tolerance genes to improve safe, green crop production and plant treatment of heavy metal soil pollution.

14.
Medicine (Baltimore) ; 100(11): e23656, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725924

RESUMO

ABSTRACT: Inflammation has been believed to contribute to coronavirus disease 2019 (COVID-19). Risk factors for death of COVID-19 pneumonia have not yet been well established.In this retrospective cohort study, we included the deceased patients in COVID-19 specialized ICU with laboratory-confirmed COVID-19 from Guanggu hospital area of Tongji Hospital from February 8th to March 30th. Demographic, clinical, laboratory, and outcome data were extracted from electronic medical records using a standard data collection form. We used Spearman rank correlation and Cox regression analysis to explore the risk factors associated with in-hospital death, especially the association between inflammatory cytokines and death.A total of 205 severe/critical COVID-19 pneumonia patients were admitted in the COVID-19 specialized ICU and 75 deceased patients were included in the final analysis. The median age of the deceasing patients was 70 years (IQR 65-79). The common symptoms were fever (78.9%), cough (70.4%), and expectoration (39.4%). The BNP and CRP levels were far beyond the normal reference range. In the Spearman rank correlation analysis, IL-8 was found to be significantly associated with the time from onset to death (rs= -0.30, P = .034) and that from admission to death (rs= -0.32, P = .019). Cox regression showed after adjusting age and sex, IL-8 levels were still significantly associated with the time from onset to death (P = .003) and that from admission to death (P  = .01).IL-8 levels were associated with in-hospital death in severe/critical COVID-19 patients, which could help clinicians to identify patients with high risk of death at an early stage.


Assuntos
/mortalidade , Interleucina-8/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Estado Terminal , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
15.
Artigo em Inglês | MEDLINE | ID: mdl-33773096

RESUMO

BACKGROUND: Nuclear receptor interaction protein (NRIP) co-localizes with acetylcholine receptor (AChR) at the neuromuscular junction (NMJ), and NRIP deficiency causes aberrant NMJ architecture. However, the normal physiological and pathophysiological roles of NRIP in NMJ are still unclear. METHODS: We investigated the co-localization and interaction of NRIP with AChR-associated proteins using immunofluorescence and immunoprecipitation assay, respectively. The binding affinity of AChR-associated proteins was analysed in muscle-restricted NRIP knockout mice and NRIP knockout muscle cells (C2C12). We further collected the sera from 43 patients with myasthenia gravis (MG), an NMJ disorder. The existence and features of anti-NRIP autoantibody in sera were studied using Western blot and epitope mapping. RESULTS: NRIP co-localized with AChR, rapsyn and α-actinin 2 (ACTN2) in gastrocnemius muscles of mice; and α-bungarotoxin (BTX) pull-down assay revealed NRIP with rapsyn and ACTN2 in complexes from muscle tissues and cells. NRIP directly binds with α subunit of AChR (AChRα) in vitro and in vivo to affect the binding affinity of AChR with rapsyn and rapsyn with ACTN2. In 43 patients with MG (age, 58.4 ± 14.5 years; female, 55.8%), we detected six of them (14.0%) having anti-NRIP autoantibody. The presence of anti-NRIP autoantibody correlated with a more severe type of MG when AChR autoantibody existed (P = 0.011). The higher the titre of anti-NRIP autoantibody, the more severe MG severity (P = 0.032). The main immunogenic region is likely on the IQ motif of NRIP. We also showed the IgG subclass of anti-NRIP autoantibody mainly to be IgG1. CONCLUSIONS: NRIP is a novel AChRα binding protein and involves structural NMJ formation, which acts as a scaffold to stabilize AChR-rapsyn-ACTN2 complexes. Anti-NRIP autoantibody is a novel autoantibody in MG and plays a detrimental role in MG with the coexistence of anti-AChR autoantibody.

16.
Poult Sci ; 100(4): 100996, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33667869

RESUMO

The cecal microbiota plays important roles in host food digestion and nutrient absorption, which may in part affect feed efficiency (FE). To investigate the composition and functional differences of cecal microbiota between high (n = 30) and low (n = 29) feed conversion ratio (FCR; metric for FE) groups, we performed 16S rRNA gene sequencing and predicted the metagenome function using Phylogenetic Investigation of Communities by Reconstruction of Unobserved Species in yellow broilers. The results showed that the 2 groups had the same prominent microbes but with differing abundance. Firmicutes, Bacteroidetes, and Actinobacteria were 3 prominent bacterial phyla in the cecal microbial community. Although there were no differences in microbial diversity, compositional differences related to FCR were found via linear discriminant analysis (LDA) effect size; the genus Bacteroides had a significantly higher abundance (LDA >2) in the high FE (HFE) group than in the low FE group. Furthermore, genus Bacteroides had a negative FCR-associated correlation (P < 0.05). Oscillospira was positively correlated with Bacteroides in both groups, whereas Dorea was negatively correlated with Bacteroides in the HFE group. Predictive functional analysis revealed that metabolic pathways such as "starch and sucrose metabolism," "phenylalanine, tyrosine and tryptophan biosynthesis," and "carbohydrate metabolism" were significantly enriched in the HFE group. The relatively subtle differences in FE-associated cecal microbiota composition suggest a possible link between cecal microbiota and FE. Moreover, Bacteroides may potentially be used as biomarkers for FE to improve growth performance in yellow broilers.

17.
Oncogene ; 40(13): 2422-2436, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33664452

RESUMO

Polycomb repressor complex 1 (PRC1) is linked to the regulation of gene expression and histone ubiquitylation conformation, which contributes to carcinogenesis. However, the upstream regulators of PRC1 biogenesis machinery remain obscure. Here, we report that the polycomb group-related mammalian gene Mel18 is a target of the protein kinase AKT. AKT phosphorylates Mel18 at T334 to disrupt the interaction between Mel18 and other PRC1 members, leading to attenuated PRC1-dependent ubiquitylation of histone H2A at Lys119. As such, PRC1 target genes, many of which are known oncogenes, are derepressed upon T334-Mel18 phosphorylation, which promotes malignant behaviours, including cell proliferation, tumour formation, migration and invasion, bone and brain metastatic lesion formation. Notably, a positive correlation between AKT activity and pT334-Mel18 is observed, and prognostic models based on p-AKT and pT334-Mel18 that predicted overall survival and distant metastasis-free survival in breast cancer patients are established. These findings have implications for understanding the role of AKT and its associated proteins in chromatin ubiquitylation, and also indicate the AKT-Mel18-H2AK119ub axis as a novel prognostic biomarker and therapeutic target for cancer patients.

18.
Oncogene ; 40(13): 2407-2421, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33664454

RESUMO

Metastatic castration-resistant prostate cancer (mCRPC) is a malignant and lethal disease caused by relapse after androgen-deprivation (ADT) therapy. Since enzalutamide is innovated and approved by US FDA as a new treatment option for mCRPC patients, drug resistance for enzalutamide is a critical issue during clinical usage. Although several underlying mechanisms causing enzalutamide resistance were previously identified, most of them revealed that drug resistant cells are still highly addicted to androgen and AR functions. Due to the numerous physical functions of AR in men, innovated AR-independent therapy might alleviate enzalutamide resistance and prevent production of adverse side effects. Here, we have identified that yes-associated protein 1 (YAP1) is overexpressed in enzalutamide-resistant (EnzaR) cells. Furthermore, enzalutamide-induced YAP1 expression is mediated through the function of chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) at the transcriptional and the post-transcriptional levels. Functional analyses reveal that YAP1 positively regulates numerous genes related to cancer stemness and lipid metabolism and interacts with COUP-TFII to form a transcriptional complex. More importantly, YAP1 inhibitor attenuates the growth and cancer stemness of EnzaR cells in vitro and in vivo. Finally, YAP1, COUP-TFII, and miR-21 are detected in the extracellular vesicles (EVs) isolated from EnzaR cells and sera of patients. In addition, treatment with EnzaR-EVs induces the abilities of cancer stemness, lipid metabolism and enzalutamide resistance in its parental cells. Taken together, these results suggest that YAP1 might be a crucial factor involved in the development of enzalutamide resistance and can be an alternative therapeutic target in prostate cancer.

19.
Cancer ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784413

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

20.
Genes Genet Syst ; 95(6): 315-321, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33642437

RESUMO

Asthma is one of the most common diseases, with a high prevalence among children. To date, systemic co-expression analysis for this disease has not been undertaken to explain its pathogenesis. Here we identified differentially expressed genes (DEGs) in 87 samples, and then constructed co-expression modules via weighted gene co-expression network analysis (WGCNA) and investigated the functional enrichment of co-expressed genes in terms of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). Meanwhile, protein-protein interaction (PPI) network and miRNA-transcription factor-target (miRNA-TF-target) regulatory network analyses were performed to screen hub genes. As a result, 3,469 DEGs were identified in this study, of which 1,860 genes were up-regulated and 1,609 genes were down-regulated. Using WGCNA, we identified two key modules, named MEbrown and MEblue, that may play important roles in asthma. Functional enrichment analysis revealed that MEbrown was enriched in 37 KEGG pathways and 472 biological processes (BPs), while MEblue was enriched in 16 KEGG pathways and 449 BPs. From PPI and miRNA-TF-target regulatory network analysis, a total of 31 TFs, seven miRNAs and 28 nodes were identified. Our findings should provide a framework of therapeutic targets for treating children with acute asthma.

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