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1.
Bioengineered ; 12(2): 10553-10567, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34854360

RESUMO

Long non-coding RNAs (LncRNAs) have crucial function in epithelial-mesenchymal transition (EMT) in pancreatic cancer. It is necessary to comprehensively analyze the potential role of EMT-related lncRNA in pancreatic cancer. In the present study, genomic data of pancreatic cancer from the TCGA database were downloaded and we found 368 EMT-related lncRNAs. According to the expression characteristics of prognostic-related lncRNAs, all samples could be divided into two clusters with different clinical outcomes and different tumor microenvironments. Moreover, an eleven EMT-related lncRNAs signature was established and verified. Patients with pancreatic cancer in the high-risk group had a shorter overall survival than those in the low-risk group and the signature could act as an independent prognostic factor. Further analysis suggested that the EMT-related lncRNAs might affect the prognosis of patients through immune mechanisms. All findings indicated that the signature and eleven lncRNAs might serve as potential prognostic biomarkers and therapeutic targets in the treatment of pancreatic cancer.

2.
Environ Toxicol ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34845814

RESUMO

Overexpression or activation of Yes-associated protein (YAP) is common in cancer cells. Thus, targeting YAP may be a strategy for cancer therapy. Licochalcone A (LicA) is a primary active compound of licorice root and is known to have medicinal effects, such as antioxidant, antibacterial, antiviral, and anticancer effects. However, the anticancer pharmacological mechanism of LicA has not been investigated in cholangiocarcinoma. In this study, we investigated the antiproliferative effect of LicA and the underlying molecular mechanism in HCCC-9810 and RBE human cholangiocarcinoma cells. Our experiments indicated that LicA suppressed the growth of cholangiocarcinoma cells through inactivation of the Hippo pathway. Pescadillo ribosomal biogenesis factor 1 (PES1) was notably upregulated and related to carcinogenesis. We also found that LicA suppressed the expression and nuclear localization of PES1, which was associated with the inhibition of YAP expression and transcriptional activity.

4.
Cell ; 184(24): 5869-5885.e25, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34758294

RESUMO

RTN4-binding proteins were widely studied as "NoGo" receptors, but their physiological interactors and roles remain elusive. Similarly, BAI adhesion-GPCRs were associated with numerous activities, but their ligands and functions remain unclear. Using unbiased approaches, we observed an unexpected convergence: RTN4 receptors are high-affinity ligands for BAI adhesion-GPCRs. A single thrombospondin type 1-repeat (TSR) domain of BAIs binds to the leucine-rich repeat domain of all three RTN4-receptor isoforms with nanomolar affinity. In the 1.65 Å crystal structure of the BAI1/RTN4-receptor complex, C-mannosylation of tryptophan and O-fucosylation of threonine in the BAI TSR-domains creates a RTN4-receptor/BAI interface shaped by unusual glycoconjugates that enables high-affinity interactions. In human neurons, RTN4 receptors regulate dendritic arborization, axonal elongation, and synapse formation by differential binding to glial versus neuronal BAIs, thereby controlling neural network activity. Thus, BAI binding to RTN4/NoGo receptors represents a receptor-ligand axis that, enabled by rare post-translational modifications, controls development of synaptic circuits.

5.
Proc Natl Acad Sci U S A ; 118(45)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34732572

RESUMO

Changes in light quality caused by the presence of neighbor proximity regulate many growth and development processes of plants. PHYTOCHROME INTERACTING FACTOR 7 (PIF7), whose subcellular localization, DNA-binding properties, and protein abundance are regulated in a photoreversible manner, plays a central role in linking shade light perception and growth responses. How PIF7 activity is regulated during shade avoidance responses has been well studied, and many factors involved in this process have been identified. However, the detailed molecular mechanism by which shade light regulates the PIF7 protein level is still largely unknown. Here, we show that the PIF7 protein level regulation is important for shade-induced growth. Two ubiquitin-specific proteases, UBP12 and UBP13, were identified as positive regulators in shade avoidance responses by increasing the PIF7 protein level. The ubp12-2w/13-3 double mutant displayed significantly impaired sensitivity to shade-induced cell elongation and reproduction acceleration. Our genetic and biochemical analysis showed that UBP12 and UBP13 act downstream of phyB and directly interact with PIF7 to maintain PIF7 stability and abundance through deubiquitination.

6.
Cell Death Dis ; 12(12): 1085, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785659

RESUMO

Nuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs.

7.
Stem Cell Reports ; 16(11): 2674-2689, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34678203

RESUMO

Pig cloning by somatic cell nuclear transfer (SCNT) frequently undergoes incomplete epigenetic remodeling during the maternal-to-zygotic transition, which leads to a significant embryonic loss before implantation. Here, we generated the first genome-wide landscapes of histone methylation in pig SCNT embryos. Excessive H3K9me3 and H3K27me3, but not H3K4me3, were observed in the genomic regions with unfaithful embryonic genome activation and donor-cell-specific gene silencing. A combination of H3K9 demethylase KDM4A and GSK126, an inhibitor of H3K27me3 writer, were able to remove these epigenetic barriers and restore the global transcriptome in SCNT embryos. More importantly, thymine DNA glycosylase (TDG) was defined as a pig-specific epigenetic regulator for nuclear reprogramming, which was not reactivated by H3K9me3 and H3K27me3 removal. Both combined treatment and transient TDG overexpression promoted DNA demethylation and enhanced the blastocyst-forming rates of SCNT embryos, thus offering valuable methods to increase the cloning efficiency of genome-edited pigs for agricultural and biomedical purposes.

8.
Ann Hematol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605949

RESUMO

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a type of low-grade malignant B-cell lymphoma. The aim of this study was to investigate the clinicopathological characteristics of thymic MALT lymphoma. We analyzed the clinical, morphological, immunophenotypical, cytogenetic, and molecular characteristics of 11 cases of thymic MALT lymphoma. The relevant literature was also reviewed. The median age of the 11 patients was 50 (range: 33-60). There was a female predominance with a female-to-male ratio of 10:1. Three patients presented with Sjögren syndrome, autoimmune thrombocytopenia purpura, and type B1 thymoma, respectively. Microscopically, thymic MALT lymphoma was characterized by epithelium-lined cysts that were surrounded by small lymphocytes, centrocyte-like cells, and monocytoid B-cells. Plasmacytic differentiation was observed in two cases. The tumor cells expressed CD20, CD79α, and BCL2. Clonal immunoglobulin genes were detected in all 8 examined cases. Fluorescence in situ hybridization (FISH) for 18q21 was performed in 7 cases, and no translocations involving 18q21 were found. Targeted gene sequencing was performed in five cases with available DNA samples, and TNFAIP3, CARD11, IGLL5, and CCND3 mutations were identified. Thymic MALT lymphoma is a rare type of B cell malignancy with a female predominance and excellent clinical outcomes. Molecular aberrations involving the NF-κB pathway are frequent in thymic MALT lymphoma, suggesting that dysregulation of the NF-κB pathway is an important mechanism underlying the pathogenesis of thymic MALT lymphoma.

9.
Oncogene ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663879

RESUMO

Human pancreatic ductal adenocarcinoma (PDAC) harboring one KRAS mutant allele often displays increasing genomic loss of the remaining wild-type (WT) allele (known as LOH at KRAS) as tumors progress to metastasis, yet the molecular ramification of this WT allelic loss is unknown. In this study, we showed that the restoration of WT KRAS expression in human PDAC cell lines with LOH at KRAS significantly attenuated the malignancy of PDAC cells both in vitro and in vivo, demonstrating a tumor-suppressive role of the WT KRAS allele. Through RNA-Seq, we identified the HIPPO signaling pathway to be positively regulated by WT KRAS in PDAC cells. In accordance with this observation, PDAC cells with LOH at KRAS exhibited increased nuclear localization and activation of transcriptional co-activator YAP1. Mechanistically, we discovered that WT KRAS expression sequestered YAP1 from the nucleus, through enhanced 14-3-3zeta interaction with phosphorylated YAP1 at S127. Consistently, expression of a constitutively-active YAP1 mutant in PDAC cells bypassed the growth inhibitory effects of WT KRAS. In patient samples, we found that the YAP1-activation genes were significantly upregulated in tumors with LOH at KRAS, and YAP1 nuclear localization predicted poor survival for PDAC patients. Collectively, our results reveal that the WT allelic loss leads to functional activation of YAP1 and enhanced tumor malignancy, which explains the selection advantage of the tumor cells with LOH at KRAS during pancreatic cancer clonal evolution and progression to metastasis, and should be taken into consideration in future therapeutic strategies targeting KRAS.

10.
Ann Surg ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34596077

RESUMO

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative hyperamylasemia greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

11.
Leuk Res ; 110: 106706, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34563944

RESUMO

Chronic lymphocytic leukemia (CLL) is a malignant disorder of mature B lymphocytes, and the precise pathogenesis is largely unknown at present. This study set out to screen the differential expression profile of long non-coding RNA (lncRNA) by microarray and explore the underlying mechanism, biological function, and clinical significance of lncRNA in CLL cells. Compared to the lncRNA expression profiles of the control group, we picked lncRNA LEF1-AS1 for further exploration. By quantitative real-time polymerase chain reaction (qRT-PCR), we validated that primary CLL cells harbor higher lncRNA LEF1-AS1 levels than normal B cells. In the two cell lines with stable overexpression of LEF1-AS1, expression of LEF1 elevated on RNA and protein level, proliferation rates increased, and apoptosis rates decreased. In primary CLL cells, mRNA expression of LEF1 decreased by qRT-PCR after negatively regulating the expression of LEF1-AS1. RNA Binding Protein Immunoprecipitation and RNA pull-down demonstrated that LncRNA LEF1-AS1 and LEF1 protein could combine especially. This thesis concludes LEF1-AS1 may be an oncogenic lncRNA that regulates the target gene LEF1 by interacting with protein LEF1. However, the prognostic significance of lncRNA LEF1-AS1 in CLL patients is still unclear.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Leucemia Linfocítica Crônica de Células B/patologia , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , RNA Antissenso/genética , RNA Longo não Codificante/genética , Idoso , Biomarcadores Tumorais/genética , Sobrevivência Celular , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/genética , Masculino , Células Tumorais Cultivadas
12.
Front Cell Dev Biol ; 9: 714718, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485300

RESUMO

Background: Recurrence of liver metastasis after pancreatectomy is often a predictor of poor prognosis. Comprehensive genomic analysis may contribute to a better understanding of the molecular mechanisms of postoperative liver metastasis and provide new therapeutic targets. Methods: A total of 67 patients from The Cancer Genome Atlas (TCGA) were included in this study. We analyzed differentially expressed genes (DEGs) by R package "DESeq2." Weighted gene co-expression network analysis (WGCNA) was applied to investigate the key modules and hub genes. Immunohistochemistry was used to analyze tumor cell proliferation index and CD4+ T cells infiltration. Results: Functional analysis of DEGs between the liver metastatic and recurrence-free groups was mainly concentrated in the immune response. The liver metastasis group had lower immune and stroma scores and a higher TP53 mutation rate. WGCNA showed that the genes in key modules related to disease-free survival (DFS) and overall survival (OS) were mainly enriched in the cell proliferation process and tumor immune response. Immunohistochemical analysis showed that the pancreatic cancer cells of patients with early postoperative liver metastasis had higher proliferative activity, while the infiltration of CD4+ T cells in tumor specimens was less. Conclusion: Our study suggested that increased immune cell infiltration (especially CD4+ T cells) and tumor cell proliferation may play an opposite role in liver metastasis recurrence after pancreatic cancer.

14.
Mediators Inflamm ; 2021: 4906768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34545276

RESUMO

Several inflammation-related factors (IRFs) have been reported to predict organ failure of acute pancreatitis (AP) in previous clinical studies. However, there are a few shortcomings in these models. The aim of this study was to develop a new prediction model based on IRFs that could accurately identify the risk for organ failure in AP. Methods. 100 patients with their clinical information and IRF data (levels of 10 cytokines, percentages of different immune cells, and data obtained from white blood cell count) were retrospectively enrolled in this study, and 94 patients were finally selected for further analysis. Univariate and multivariate analysis were applied to evaluate the potential risk factors for the organ failure of AP. The area under the ROC curve (AUCs), sensitivity, and specificity of the relevant model were assessed to evaluate the prediction ability of IRFs. A new scoring system to predict the organ failure of AP was created based on the regression coefficient of a multivariate logistic regression model. Results. The incidence of OF in AP patients was nearly 16% (15/94) in our derivation cohort. Univariate analytic data revealed that IL6, IL8, IL10, MCP1, CD3+ CD4+ T lymphocytes, CD19+ B lymphocytes, PCT, APACHE II score, and RANSON score were potential predictors for AP organ failure, and IL6 (P = 0.038), IL8 (P = 0.043), and CD19+B lymphocytes (P = 0.045) were independent predictors according to further multivariate analysis. In addition, a preoperative scoring system (0-11 points) was constructed to predict the organ failure of AP using these three factors. The AUC of the new score system was 0.86. The optimal cut-off value of the new scoring system was 6 points. Conclusions. Our prediction model (based on IL6, IL8, and CD19+ B Lymphocyte) has satisfactory working efficiency to identify AP patients with high risk of organ failure.

15.
Cancer Med ; 10(20): 7320-7329, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34480528

RESUMO

BACKGROUND: Previous studies have shown that marital status was associated with stages and survival in patients with melanoma or Merkel cell carcinoma. To date, the impacts of marital status on stage and survival in patients with mycosis fungoides (MF) have not been determined yet. METHODS: A total of 3375 eligible cases diagnosed from 2004 to 2015 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Association of marital status with stage and survival in patients with MF was analyzed. RESULTS: Married patients were more likely to be diagnosed at T1 stage (p = 0.041). And married patients were less likely to present with lymph node involvement (p = 0.007). More favorable overall survival (p < 0.001) and cancer-specific survival (p < 0.001) were demonstrated in married patients as compared with divorced patients or widowed patients. A clinically feasible prognostic model including marital status, age, sex, race, and stage at presentation was constructed. CONCLUSION: Married marital status was associated with earlier stage at diagnosis and longer survival compared with divorced or widowed marital status in patients with MF.

16.
J Gastroenterol ; 56(10): 938-948, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34453212

RESUMO

BACKGROUND: Prophylactic somatostatin to reduce the incidence of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy remains controversial. We assessed the preventive efficacy of somatostatin on clinically relevant postoperative pancreatic fistula in intermediate-risk patients who underwent pancreaticoduodenectomy at pancreatic centres in China. METHODS: In this multicentre, prospective, randomised controlled trial, we used the updated postoperative pancreatic fistula classification criteria and cases were confirmed by an independent data monitoring committee to improve comparability between centres. The primary endpoint was the rate of clinically relevant postoperative pancreatic fistula within 30 days after pancreaticoduodenectomy. RESULTS: Eligible patients (randomised, n = 205; final analysis, n = 199) were randomised to receive postoperative intravenous somatostatin (250 µg/h over 120 h; n = 99) or conventional therapy (n = 100). The primary endpoint was significantly lower in the somatostatin vs control group (n = 13 vs n = 25; 13% vs 25%, P = 0.032). There were no significant differences for biochemical leak (P = 0.289), biliary fistula (P = 0.986), abdominal infection (P = 0.829), chylous fistula (P = 0.748), late postoperative haemorrhage (P = 0.237), mean length of hospital stay (P = 0.512), medical costs (P = 0.917), reoperation rate (P > 0.99), or 30 days' readmission rate (P = 0.361). The somatostatin group had a higher rate of delayed gastric emptying vs control (n = 33 vs n = 21; 33% vs 21%, P = 0.050). CONCLUSIONS: Prophylactic somatostatin treatment reduced clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy. TRIAL REGISTRATION: NCT03349424.

17.
J Exp Clin Cancer Res ; 40(1): 261, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416910

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are becoming a unique member of non-coding RNAs (ncRNAs) with emerging evidence of their regulatory roles in various cancers. However, with regards to pancreatic ductal adenocarcinoma (PDAC), circRNAs biological functions remain largely unknown and worth investigation for potential therapeutic innovation. METHODS: In our previous study, next-generation sequencing was used to identify differentially expressed circRNAs in 3 pairs of PDAC and adjacent normal tissues. Further validation of circRHOBTB3 expression in PDAC tissues and cell lines and gain-and-loss function experiments verified the oncogenic role of circRHOBTB3. The mechanism of circRHOBTB3 regulatory role was validated by pull-down assays, RIP, luciferase reporter assays. The autophagy response of PANC-1 and MiaPaca-2 cells were detected by mCherry-GFP-LC3B labeling and confocal microscopy, transmission electron microscopy and protein levels of LC3B or p62 via Western blot. RESULTS: circRHOBTB3 is highly expressed in PDAC cell lines and tissues, which also promotes PDAC autophagy and then progression in vitro and in vivo. Mechanistically, circRHOBTB3 directly binds to miR-600 and subsequently acts as a miRNA-sponge to maintain the expression level of miR-600-targeted gene NACC1, which facilitates the autophagy response of PDAC cells for adaptation of proliferation via Akt/mTOR pathway. Moreover, the RNA-binding protein FUS (FUS) directly binds to pre-RHOBTB3 mRNA to mediate the biogenesis of circRHOBTB3. Clinically, circRHOBTB3, miR-600 and NACC1 expression levels are correlated with the prognosis of PDAC patients and serve as independent risk factors for PDAC patients. CONCLUSIONS: FUS-mediated circRHOBTB3 functions as a tumor activator to promote PDAC cell proliferation by modulating miR-600/NACC1/Akt/mTOR axis regulated autophagy.

18.
Transl Oncol ; 14(10): 101176, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273750

RESUMO

The 11q deletion (del(11q)) is a conventional cytogenetic aberration observed in chronic lymphocytic leukemia (CLL) patients. However, the prevalence and the prognostic value of del(11q) are still controversial. In this research, we retrospectively explored the prevalence, association, and prognostic significance of del(11q) in 352 untreated and 99 relapsed/refractory Chinese CLL patients. Totally 11.4% of untreated and 19.2% of relapsed/refractory patients harbored del(11q). Del(11q) was more common in patients with ß2-microglobulin > 3.5 mg/L, positive CD38, positive zeta-chain associated protein kinase 70, unmutated immunoglobulin heavy variable-region gene and ataxia telangiectasia mutated mutation. Kaplan-Meier method and univariate Cox regression indicated that del(11q) was an independent prognostic factor for overall survival (OS). Based on the results of univariate Cox regression analysis, two nomograms that included del(11q) were established to predict survival. Desirable area under curve of receiver operating characteristic curves was obtained in the training and validation cohorts. In addition, the calibration curves for the probability of survival showed good agreement between the prediction by nomogram and actual observation. In summary, the prevalence of del(11q) is relatively low in our cohort and del(11q) is an unfavorable prognostic factor for untreated CLL patients. Besides, these two nomograms could be used to accurately predict the prognosis of untreated CLL patients.

19.
Gland Surg ; 10(6): 1852-1864, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34268070

RESUMO

Background: Organ/space surgical site infections (OSSI) after pancreaticoduodenectomy (PD) are not rare events. The role of diagnosis and treatment for pancreatic and biliary diseases with an endoscopic retrograde cholangio-pancreatography (ERCP) procedure is currently controversial. However, the ERCP procedure might play a role in surgical outcomes after PD. Methods: We conducted a retrospective cohort study for patients who underwent PD in the First Affiliated Hospital with the Nanjing Medical University from 1st September 2012 to 31st January 2018. The relationship between ERCP exposure and OSSI after PD was analyzed by univariate and forward stepwise multivariate logistic regression model. Results: Of the 1,365 patients who underwent PD, 136 developed OSSI (10.0%). We found that ERCP exposure before PD (EEBPD) was significantly associated with an increased incidence rate of post-operative pancreas fistula (POPF) [24.2% (23/95) vs. 14.9% (189/1,270), risk ratio (RR) =1.63, 95% confidence interval (CI), 1.11-2.38, P=0.015]. Hypertension, a higher level of preoperative low-density lipoprotein (LDL) and creatinine (Cr) were associated with elevated risks of post-operative OSSI [adjusted odds ratio (Adj-OR) (95% CI) were 1.59 (1.09-2.32), 1.70 (1.16-2.51), 1.99 (1.36-2.92)], whereas a preoperatively higher level of aspartate aminotransferase (AST) would decrease the risk [Adj-OR (95% CI), 0.62 (0.42-0.91)]. Remarkably, EEBPD would significantly increase and more than double the OSSI risk [Adj-OR (95% CI), 2.56 (1.46-4.47)] especially if it was within 14 days before surgery (Spearman =-0.698, P<0.001). Conclusions: ERCP, as an independent risk factor, significantly increased the risk of post-operative OSSI after PD if it is performed within 14 days prior to surgery. Our findings would assist clinical decision-making, and improve OSSI control and prevention.

20.
Stem Cell Reports ; 16(7): 1686-1696, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34214484

RESUMO

Human extended pluripotent stem cells (EPSCs), with bidirectional chimeric ability to contribute to both embryonic and extraembryonic lineages, can be obtained and maintained by converting conventional pluripotent stem cells using chemicals. However, the transition system is based on inactivated mouse fibroblasts, and the underlying mechanism is not clear. Here we report a Matrigel-based feeder-free method to convert human embryonic stem cells and induced pluripotent stem cells into EPSCs and demonstrate the extended pluripotency in terms of molecular features, chimeric ability, and transcriptome. We further identify chemicals targeting glycolysis and histone methyltransferase to facilitate the conversion to and maintenance of feeder-free EPSCs. Altogether, our data not only establish a feeder-free system to generate human EPSCs, which should facilitate the mechanistic studies of extended pluripotency and further applications, but also provide additional insights into the transitions among different pluripotent states.

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