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1.
J Cell Mol Med ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33534963

RESUMO

Inflammation is a biological process that exists in a large number of diseases. If the magnitude or duration of inflammation becomes uncontrolled, inflammation may cause pathological damage to the host. HMGB1 and NF-κB have been shown to play pivotal roles in inflammation-related diseases. New drugs aimed at inhibiting HMGB1 expression have become a key research focus. In the present study, we showed that paeonol (Pae), the main active component of Paeonia suffruticosa, decreases the expression of inflammatory cytokines and inhibits the translocation of HMGB1 induced by lipopolysaccharide (LPS). By constructing HMGB1-overexpressing (HMGB1+ ) and HMGB1-mutant (HMGB1m ) RAW264.7 cells, we found that the nuclear HMGB1 could induce an LPS-tolerant state in RAW264.7 cells and that paeonol had no influence on the expression of inflammatory cytokines in HMGB1m RAW264.7 cells. In addition, the anti-inflammatory property of paeonol was lost in HMGB1 conditional knockout mice, indicating that HMGB1 is a target of paeonol and a mediator through which paeonol exerts its anti-inflammatory function. Additionally, we also found that HMGB1 and P50 competitively bound with P65, thus inactivating the NF-κB pathway. Our research confirmed the anti-inflammation property of paeonol and suggests that inhibiting the translocation of HMGB1 could be a new strategy for treating inflammation.

2.
Med. oral patol. oral cir. bucal (Internet) ; 26(1): e49-e55, ene. 2021. ilus, tab
Artigo em Inglês | IBECS-Express | IBECS | ID: ibc-ET6-1985

RESUMO

BACKGROUND: The aim of this study was to investigate the clinicopathologic features of primary intraosseous squamous cell carcinoma arising from an odontogenic keratocyst (PIOSCC ex OKC) and comprehensively improve the understanding of this disease. MATERIAL AND METHODS: We retrospectively investigated five cases of PIOSCC ex OKC at Peking University School and Hospital of Stomatology. We also conducted a systematic review of studies on PIOSCC ex OKC by using online databases from their inception until February 2020. RESULTS: In our series of five cases, all lesions were located in the mandible. Three cases (60%) showed recurrent OKCs and two cases (40%) showed primary OKCs. During the follow-up period, one patient died of local relapse. No patients developed metastasis. On the basis of our literature survey, we selected 22 articles reporting 29 patients with PIOSCC ex OKC. Seven of these patients (24.1%) showed local recurrence, three patients (10.3%) developed cervical metastasis, three patients (10.3%) developed distant metastasis (in the pleura in one case and in the lung in two cases), and seven patients died from the disease during the follow-up period. The disease-specific 5-year survival rate in the study group was 53.2%. Through univariate and multivariate analysis, local recurrence was identified as the only significant independent prognostic factor for survival (P < 0.05). CONCLUSIONS: The results suggest that PIOSCC ex OKC is a rare intermediate-grade malignancy. Although elective neck dissection is typically unnecessary, adequate therapy should be applied to achieve the lowest local recurrence rate possible to ensure a favorable survival rate


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3.
Cell Signal ; 80: 109900, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33370582

RESUMO

Low shear stress (LSS) plays a critical role in the development of atherosclerotic plaques and vascular inflammation. Previous studies have reported Akt phosphorylation induced by LSS. However, the mechanism and role of Akt activation remains unclear in LSS-induced endothelial dysfunction. In this study, our results demonstrated the increased phosphorylation of IKKε, TBK1 and Akt in HUVECs exposed to LSS. Furthermore, IKKε silencing using small interfering RNAs significantly reduced LSS-induced Akt phosphorylation. In contrast, silencing of TBK1 or inhibition of PI3K and mTORC2 had no effect on LSS-induced Akt phosphorylation. Notably, Akt inhibition markedly diminished LSS-induced expression of ICAM-1, VCAM-1 and MCP-1, as well as LSS-induced IRF3 phosphorylation and nuclear translocation, without affecting the activation of NF-κB and STAT1. Moreover, endothelial cell specific Akt overexpression mediated by adeno-associated virus markedly increased intimal ICAM-1 and IRF3 expression at LSS area of partially ligated carotid artery in mice. In brief, our findings suggest that LSS-induced Akt phosphorylation is positively regulated by IKKε and promotes IRF3 activation, leading to endothelial inflammation.

4.
Life (Basel) ; 10(12)2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33287205

RESUMO

Solanum nigrum L., a hyperaccumulator of cadmium (Cd), is regarded as a promising candidate for phytoremediation of heavy metal pollution. In the present study, the hairy roots of Solanum nigrum L. were selected as a model plant system to study the potential application of Iron-regulated Transporter Gene (IRT1) for the efficient phytoremediation of Cd pollution. The transgenic hairy roots of Solanum nigrum L. expressing the IRT1 gene from Arabidopsis thaliana were successfully obtained via the Agrobacterium tumegaciens-mediated method. Expression of IRT1 reduced Cd stress-induced phytotoxic effects. Significantly superior root growth, increased antioxidant enzyme activities, decreased reactive oxygen species (ROS) levels, and less cell apoptosis were observed in the transgenic hairy roots of Solanum nigrum L. compared to the wild-type lines under Cd stress. Enhanced Cd accumulation was also carried out in the transgenic hairy roots compared to the control (886.8 µg/g vs. 745.0 µg/g). These results provide an important understanding of the Cd tolerance mechanism of transgenic IRT1 hairy roots of Solanum nigrum L., and are of particular importance to the development of a transgenic candidate for efficient phytoremediation process.

5.
Zhongguo Gu Shang ; 33(11): 1022-6, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269851

RESUMO

Periprosthetic infection after hip replacement is a clinical catastrophic disease, which often leads to the failure of the prosthesis. It needs the combination of systemic antibiotics to cure the infection, which brings huge burden to doctors and patients. There are strict indications for debridement and one-stage revision of the prosthesis, and few cases meet the requirements. The second revision is still the gold standard for the treatment of periprosthetic infection. It is suitable for all infection conditions and has a high success rate. On the second phase of renovation, the antibiotic sustained release system plays a key role, and the carrier of antibiotic sustained-release system is the focus of current research, including classic bone cement and absorbable biomaterials. Bone cement has strong mechanical strength, but the antibiotic release shows a sharp decline trend; the absorbable biomaterials can continuously release antibiotics with high concentration, but the mechanical strength is poor, so it could not use alone. The combination of bone cement and absorbable biomaterials will be an ideal antibiotic carrier. PMMA is the most commonly used antibiotic carrier, but the antibiotic release concentration is decreased sharply after 24 hours. It will be difficult to control the infection and increase the risk of bacterial resistance if it is lower than the minimum inhibitory concentration. The biodegradable materials can release antibiotics completely, with long release time and high concentration, but low mechanical strength. Antibiotic spacer plays an important role in the control of infection. In the future, how to further extend the antibiotic release time of antibiotic sustained-release system, increase the amount of antibiotic release and maintain the mechanical strength of the material will be studied.

6.
Adv Sci (Weinh) ; 7(23): 2002155, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304759

RESUMO

Canavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N-acetyl-L-aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)-based cell therapy is developed for CD. A functional ASPA gene is introduced into patient iPSC-derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN-mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival. These genetically engineered patient iPSC-derived cellular products are promising cell therapies for CD. This study has the potential to bring effective cell therapies, for the first time, to Canavan disease children who have no treatment options. The approach established in this study can also benefit many other children who have deadly genetic diseases that have no cure.

7.
Stat Med ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159355

RESUMO

Biomarkers of interest in urine, serum, or other biological matrices often have an assay limit of detection. When concentration levels of the biomarkers for some subjects fall below the limit, the measures for those subjects are censored. Censored data due to detection limits are very common in public health and medical research. If censored data from a single exposure group follow a normal distribution or follow a normal distribution after some transformations, Tobit regression models can be applied. Given a Tobit regression model and a detection limit, the proportion of censored data can be determined. However, in practice, it is common that the data can exhibit excessive censored observations beyond what would be expected under a Tobit regression model. One common cause is heterogeneity of the study population, that is, there exists a subpopulation who lack such biomarkers and their values are always under the detection limit, and hence are censored. In this article, we develop a new test for testing such latent class under a Tobit regression model by directly comparing the amount of observed censored data with what would be expected under the Tobit regression model. A closed form of the test statistic as well as its asymptotic properties are derived based on estimating equations. Simulation studies are conducted to investigate the performance of the new test and compare the new one with the existing ones including the Wald test, likelihood ratio test, and score test. Two real data examples are also included for illustrative purpose.

8.
BMC Anesthesiol ; 20(1): 294, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33250060

RESUMO

BACKGROUND: Preoperative intravenous rehydration for patients with pheochromocytomas and paragangliomas (PPGLs) is widely used in many medical centers, but its usefulness has not been well evaluated. The objective of this study was to compare the perioperative hemodynamics and early outcome between patients who received preoperative intravenous rehydration and those without for resection of PPGLs. METHODS: In this retrospective propensity score-matched cohort study, the data of patients who underwent surgery for PPGLs were collected. Patients were divided into two groups depending on whether they received or did not receive intravenous rehydration preoperatively. The primary endpoint was intraoperative hypotension, described as the cumulative time of mean arterial pressure < 65 mmHg averaged by surgery duration. RESULTS: Among 231 enrolled patients, 113 patients received intravenous rehydration of ≥2000 ml daily for ≥2 days before surgery and 118 patients who did not have any intravenous rehydration before surgery. After propensity score matching, 85 patients remained in each group. The median cumulative time of mean arterial pressure < 65 mmHg averaged by surgery duration was not significantly different between rehydrated patients and non-rehydrated patients (median 3.0% [interquartile range 0.2-12.2] versus 3.8% [0.0-14.2], median difference 0.0, 95%CI - 1.2 to 0.8, p = 0.909). The total dose of catecholamines given intraoperatively, volume of intraoperative fluids, intraoperative tachycardia and hypertension, percentage of patients who suffered from postoperative hypotension, postoperative diuretics use, and postoperative early outcome between the two groups were not significantly different either. CONCLUSIONS: For patients with PPGLs, preoperative intravenous rehydration failed to optimize perioperative hemodynamics or improve early outcome.

9.
World J Gastrointest Oncol ; 12(11): 1237-1254, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33250958

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer (GC) has not been fully elucidated. AIM: To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC. METHODS: Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pcHOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXD-AS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis. RESULTS: The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway. CONCLUSION: These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.

10.
Int Immunopharmacol ; 89(Pt B): 107068, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33091813

RESUMO

Phagocytosis is a basic immune response to the pathogens invading. Immunosuppression may occur in diseases like sepsis and cancer, and cause a low phagocytic ability of phagocytes. High mobility group protein B1 (HMGB1) is a DNA chaperone which is closely related to the phagocytosis. Nonetheless, its influence on phagocytosis is still controversial. We found that paeonol could inhibit the translocation of HMGB1 from the nucleus to the cytoplasm, it may have an impact on phagocytosis. In the present study, we performed in vivo and in vitro experiments to investigate the influence of paeonol on phagocytosis. Zymosan was used to test the phagocytic function of macrophages. Our results showed that paeonol promotes the phagocytosis of macrophages through confining HMGB1 to the nucleus. Through interacting with P53, the nuclear HMGB1 keep it in the nucleus and decrease the negative influence of P53 on the phosphorylation of Focal Adhesion Kinase (FAK). The increasing of phosphorylated FAK promotes the formation of pseudopod and enhances the phagocytic ability of macrophages.

11.
Chemistry ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044771

RESUMO

The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)-sarain A was achieved. This approach featured the employment of an organocatalytic asymmetric Michael addition reaction and a nitrogen-to-carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate. The tricyclic intermediate contained all the required functionalities for elaborating into (+)-sarain A.

12.
J Vasc Interv Radiol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33012652

RESUMO

PURPOSE: To retrospectively compare the safety and efficacy of a covered self-expandable metal stent (CSEMS) with a transhepatic fixation string and a large-bore catheter for benign biliary anastomotic stricture after hepatobiliary surgery. MATERIALS AND METHODS: From March 2012 to June 2017, 49 patients with benign biliary anastomotic strictures, untreatable with endoscopy, were included. Twenty-three patients (catheter group) were treated with a large-bore catheter (with progressive catheter upsizing to 16-18 Fr), whereas 26 patients (stent group) were treated by CSEMS (10-mm stent) placement. Technical success, clinical success, primary patency, recurrent strictures, complication rate, and catheter or stent indwelling time were compared between the groups. RESULTS: Technical success and clinical success were achieved in all patients. In the stent group, stent retrieval was successful in all patients. The overall complication rate was 24.5% (catheter group vs. stent group, 30.4% vs. 19.2%; P = .363). Stent migration occurred in 1 patient during follow-up (1/26, 3.8%). The mean indwelling time was 10.3 ± 3.0 months (range, 8-16 months; median, 10 months) in the catheter group and 4.0 ± 1.2 months (range, 3-7 months; median, 4 months) in the stent group (P < .001). Recurrent strictures occurred in 10 (43.5%) patients in the catheter group and 4 (15.4%) patients in the stent group (P = .030). The 1- and 3-year primary patency rates were 82.6% and 69.3% in the catheter group and 92.3% and 84.4% in the stent group (P = .042). CONCLUSIONS: Percutaneous placement of a retrievable CSEMS showed superior intermediate-term outcomes over a large-bore catheter in patients with benign biliary anastomotic strictures.

13.
Front Oncol ; 10: 1657, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014829

RESUMO

Estrogen and progesterone regulate the growth and development of human tissues, including the reproductive system and breasts, through estrogen and progesterone receptors, respectively. These receptors are also important indicators for the clinical prognosis of breast cancer and various reproductive cancers. Many studies have reported that cancer stem cells (CSCs) play a key role in tumor initiation, progression, metastasis, and recurrence. Although the role of estrogen and progesterone in human organs and various cancers has been studied, the molecular mechanisms underlying the action of these hormones on CSCs remain unclear. Therefore, further elucidation of the effects of estrogen and progesterone on CSCs should provide a new direction for developing pertinent therapies. In this review, we summarize the current knowledge on the estrogen and progesterone axis involved in cancer stemness and discuss potential therapeutic strategies to inhibit CSCs by targeting relevant pathways.

14.
Adv Sci (Weinh) ; 7(19): 2001108, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33042743

RESUMO

Nanovaccines have attracted booming interests in vaccinology studies, but the profound impacts of their delivery mode on immune response remain unrealized. Herein, immunostimulatory CpG-modified tumor-derived nanovesicles (CNVs) are used as a nanovaccine testbed to initially evaluate the impacts of three distinct delivery modes, including mono-pulse CNVs, staggered-pulse CNVs, and gel-confined CNVs. Fundamentally, delivery mode has enormous impacts on the immunomodulatory effects, altering the spatiotemporal distribution of nanovaccine residence and dendritic cell-T cell interaction in lymph nodes, and finally affecting subsequent T cell-mediated immune performance. As a result, the gel-confined delivery mode offers the best therapeutic performance in multiple tumor models. When extending evaluation to examine how the various delivery modes impact the performance of liposome-based nanovaccines, similar trends in intralymph node distribution and antitumor effect are observed. This work provides a strong empirical foundation that nanovaccine researchers should position delivery mode near the top of their considerations for the experimental design, which should speed up nanovaccine development and facilitate efficient selection of appropriate delivery modes in the clinic.

15.
World J Clin Cases ; 8(15): 3365-3371, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32874994

RESUMO

BACKGROUND: Gastrointestinal stromal tumors are lesions that originate from digestive tract walls. Several laparoscopic techniques, including local resections, wedge resections and partial gastrectomies, have been used successfully. However, there are no reports on laparoscopic segmental gastrectomy for gastrointestinal stromal tumors. CASE SUMMARY: We present our analysis of 17 patients who were admitted to our hospital from January 2014 to December 2018. All tumors were located in the corpus and antrum of the stomach, close to the lesser curvature of the stomach. The tumors originated from the anterior wall in nine cases and from the posterior wall of the stomach in eight cases. Laparoscopic segmental gastrectomy and end-to-end anastomosis between the proximal and the distal residual stomach were used in all patients. The mean operative time was 112.4 min. The mean length of hospital stay was 4.6 d. Mean operative blood loss was 73.5 mL. There were no leaks, no postoperative bleeding nor need for reintervention. Mean postoperative follow-up was 35.4 mo. The Visick grading index showed fewer gastrointestinal symptoms 3 mo after surgery. Two patients (11.8%) had reflux esophagitis and gastritis. CONCLUSION: Laparoscopic segmental gastrectomy may be a new function-preserving gastrectomy that is feasible for treatment of gastrointestinal stromal tumors that grow in the middle third of the stomach and on the lesser stomach curvature.

16.
J Craniofac Surg ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32890148

RESUMO

The frequent refractory response of patients to the treatment of medication-related osteonecrosis of the jaw (MRJON) has attracted clinicians' attention to several treatments. However, they are at best, palliative, and have a higher failure rate than previous treatments. The present meta-analysis was performed to evaluate the clinical effectiveness of autologous platelet concentrates (APCs) combined with surgery in the treatment of MRONJ. The authors conducted a meta-analysis involving a systematic search of PubMed, EMBASE, Wiley Online Library and the Cochrane Library for eligible studies from their inception to November 2019, in accordance with preselected criteria. The inverse variance method was applied to fixed or random effects models based on the heterogeneity of the studies. Thirteen studies that investigated APCs in the treatment of MRONJ were eligible for inclusion in the meta-analysis of 223 patients and 33 lesions. The pooled success rate of APCs combined with surgery for MRONJ was 90% (95%CI, 80%-97%) and the pooled OR was 7.67 (95%CI, 2.10-27.98), indicating the combination was 7.67 times more effective than surgery alone. The results suggest that the use of APCs is a promising therapeutic regimen, as it provided additional benefits to surgery in the treatment of MRONJ. To achieve the benefits, a tension-free primary closure of the soft tissue is recommended as well. Randomized studies with large sample sizes is warranted to confirm our finding.

17.
Biom J ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32965696

RESUMO

Binomial regression models are commonly applied to proportion data such as those relating to the mortality and infection rates of diseases. However, it is often the case that the responses may exhibit excessive zeros; in such cases a zero-inflated binomial (ZIB) regression model can be applied instead. In practice, it is essential to test if there are excessive zeros in the outcome to help choose an appropriate model. The binomial models can yield biased inference if there are excessive zeros, while ZIB models may be unnecessarily complex and hard to interpret, and even face convergence issues, if there are no excessive zeros. In this paper, we develop a new test for testing zero inflation in binomial regression models by directly comparing the amount of observed zeros with what would be expected under the binomial regression model. A closed form of the test statistic, as well as the asymptotic properties of the test, is derived based on estimating equations. Our systematic simulation studies show that the new test performs very well in most cases, and outperforms the classical Wald, likelihood ratio, and score tests, especially in controlling type I errors. Two real data examples are also included for illustrative purpose.

18.
Taiwan J Obstet Gynecol ; 59(5): 718-722, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917324

RESUMO

OBJECTIVE: With the rapid rising prevalence, gestational diabetes mellitus (GDM) has become one of the leading causes of maternal and child mortality and morbidity worldwide. The present study aimed to analyze GDM-related risk factors for early intervention. MATERIALS AND METHODS: From January to June 2018, a total of 250 pregnant women from Chengdu Second People's Hospital were enrolled in the study. According to the diagnostic criteria for GDM, they were assigned into GDM group (n = 48) and non-GDM group (n = 202). The clinical data and biochemical indicators were compared between GDM group and non-GDM group, and Logistic regression analysis was performed to analyze the risk factors of GDM. RESULTS: GDM group was significantly higher than non-GDM group in the age, pregnancy times, pre-pregnancy body mass index (BMI), low-density lipoprotein cholesterol (LDL-C) level, history of diabetes mellitus in first-degree relatives, incidence of subclinical hypothyroidism (SCH) and the positive rate of thyroid peroxidase antibody (TPOAb) (P < 0.05), whereas was conspicuously lower than non-GDM group in the education level above junior college (P < 0.05). The results of Logistic regression analysis revealed that the age [odds ratios (OR) = 1.125, 95% confidential interval (CI) = 1.019-1.241, P = 0.020], pre-pregnancy BMI (OR = 1.280, 95%CI = 1.118-1.466, P < 0.001), history of diabetes mellitus in first-degree relatives (OR = 4.938, 95%CI = 1.418-17.196, P = 0.012) and TPOAb (+) (OR = 4.849, 95%CI = 1.742-13.501, P = 0.003) were the risk factors of GDM. CONCLUSIONS: Advanced age, pre-pregnancy BMI overweight, history of diabetes mellitus in first-degree relatives and TPOAb (+) are associated with an increased risk of GDM.

19.
BMC Med Genomics ; 13(1): 118, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831081

RESUMO

BACKGROUND: DNA methylation is a common chemical modification of DNA in the carcinogenesis of hepatocellular carcinoma (HCC). METHODS: In this bioinformatics analysis, 348 liver cancer samples were collected from the Cancer Genome Atlas (TCGA) database to analyse specific DNA methylation sites that affect the prognosis of HCC patients. RESULTS: 10,699 CpG sites (CpGs) that were significantly related to the prognosis of patients were clustered into 7 subgroups, and the samples of each subgroup were significantly different in various clinical pathological data. In addition, by calculating the level of methylation sites in each subgroup, 119 methylation sites (corresponding to 105 genes) were selected as specific methylation sites within the subgroups. Moreover, genes in the corresponding promoter regions in which the above specific methylation sites were located were subjected to signalling pathway enrichment analysis, and it was discovered that these genes were enriched in the biological pathways that were reported to be closely correlated with HCC. Additionally, the transcription factor enrichment analysis revealed that these genes were mainly enriched in the transcription factor KROX. A naive Bayesian classification model was used to construct a prognostic model for HCC, and the training and test data sets were used for independent verification and testing. CONCLUSION: This classification method can well reflect the heterogeneity of HCC samples and help to develop personalized treatment and accurately predict the prognosis of patients.

20.
Environ Microbiol ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32813277

RESUMO

Mitogen-activated protein kinase (MAPK) cascades are highly conserved in eukaryotic cells and are known to play crucial roles in the regulation of various cellular processes. However, compared with kinase-mediated phosphorylation, dephosphorylation catalysed by phosphatases has not been well characterized in filamentous fungi. In this study, we identified five MAPK pathway-related phosphatases (Msg5, Yvh1, Ptp1, Ptp2 and Oca2) and characterized their functions in Aspergillus flavus, which produces aflatoxin B1 (AFB1 ), one of the most toxic and carcinogenic secondary metabolites. These five phosphatases were identified as negative regulators of MAPK (Slt2, Fus3 and Hog1) pathways. Deletion of Msg5 and Yvh1 resulted in significant defects in conidiation, sclerotia formation, aflatoxin production and crop infection. Additionally, double knockout mutants (ΔMsg5/ΔPtp1, ΔMsg5/ΔPtp2 and ΔMsg5/ΔOca2) displayed similar defects to those observed in the ΔMsg5 single mutant, indicating that Msg5 plays a major role in the regulation of development and pathogenicity in A. flavus. Importantly, we found that the active site at C439 is essential for the function of the Msg5 phosphatase. Furthermore, the MAP kinase Fus3 was found to be involved in the regulation of development, aflatoxin biosynthesis and pathogenicity, and its conserved phosphorylation residues (Thr and Tyr) were critical for the full range of its functions in A. flavus. Overall, our results reveal that MAPK related tyrosine phosphatases play important roles in the regulation of development, secondary metabolism and pathogenicity in A. flavus, and could be developed as potential targets for preventing damage caused by this fungal pathogen.

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