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1.
Methods Mol Biol ; 2170: 143-154, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32797457

RESUMO

MicroRNAs (miRNAs) play important roles in development in plants, and some miRNAs show developmentally regulated organ- and tissue-specific expression patterns. Therefore, in situ detection of mature miRNAs is important for understanding the functions for both miRNAs and their targets. The construction of promoter-reporter fusions and examination of their in planta expression has been widely used and the results obtained thus far are rather informative; however, in some cases, the length of promoter that contains entire regulatory elements is difficult to determine. In addition, traditional in situ hybridization with the antisense RNA fragment as the probe usually fails to detect miRNAs, because the mature miRNAs are too short (~21-nucleotides) to exhibit stable hybridization signals. In recent years, the Locked nucleic acid (LNA) modified DNA probe has been successfully used in animals and plants to detect small RNAs. Here, we describe a modified protocol using LNA-modified DNA probes to detect mature miRNAs in plant tissues, including the design of LNA probes and detailed steps for the in situ hybridization experiment, using Arabidopsis miR165 as an example.

2.
Methods Mol Biol ; 2195: 263-275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32852769

RESUMO

Germ cell tumors (GCTs) are a rare disease, but they account for 15% of all malignancies diagnosed during adolescence. The biological mechanisms underpinning their development are only starting to be explored. Current GCT treatment may be associated with significant toxicity. Therefore, there is an urgent need to understand the molecular basis of GCT and identify biomarkers to tailor the therapy for individual patients. However, this research is severely hamstrung by the rarity of GCTs in individual hospitals/institutes. A publicly available genomic data commons with GCT datasets compiled from different institutes/studies would be a valuable resource to facilitate such research. In this study, we first reviewed publicly available web portals containing GCT genomics data, focusing on comparing data availability, data access, and analysis tools, and the limitations of using these resources for GCT molecular studies. Next, we specifically designed a GCT data commons with a web portal, GCT Explorer, to assist the research community to store, manage, search, share, and analyze data. The goal of this work is to facilitate GCT molecular basis exploration and translational research.

3.
ChemSusChem ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179864

RESUMO

Searching for high-efficiency nonprecious bifunctional electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is paramount for the advancement of water electrolysis technologies and the associated renewable energy devices. Modulation of electronic structure of an electrocatalyst via heterointerface engineering represents an efficient strategy to improve its electrocatalytic performance. Herein, a feasible hydrothermal synthesis of a novel heterostructured catalyst was demonstrated, comprising CoS2 nanocubes and vertically aligned MoS2 nanosheet arrays directly grown on flexible and conductive carbon cloth (CC) substrate (denoted as CoS2 /MoS2 @CC). Thanks to the elaborate interface engineering and vertically aligned nanosheet arrayed architecture, the resultant self-supported CoS2 /MoS2 @CC electrode possessed enriched exposed active sites, modulated electronic configuration, multidimensional mass transport channels, and outstanding mechanical strength, thereby affording exceptional electrocatalytic performances towards the HER and OER in alkaline electrolyte with overpotentials of 71 and 274 mV at 10 mA cm-2 , respectively. In addition, a two-electrode electrolyzer assembled by CoS2 /MoS2 @CC required a cell voltage of 1.59 V at 10 mA cm-2 with nearly 100 % faradaic efficiency and remarkable durability, showing great potential for scalable and economical water electrolysis.

4.
Oncogene ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199827

RESUMO

Rhabdomyosarcoma (RMS) is a devastating pediatric sarcoma. The survival outcomes remain poor for patients with relapsed or metastatic disease. Effective targeted therapy is lacking due to our limited knowledge of the underlying cellular and molecular mechanisms leading to disease progression. In this study, we used functional assays in vitro and in vivo (zebrafish and xenograft mouse models) to demonstrate the crucial role of HDAC6, a cytoplasmic histone deacetylase, in driving RMS tumor growth, self-renewal, and migration/invasion. Treatment with HDAC6-selective inhibitors recapitulates the HDAC6 loss-of-function phenotypes. HDAC6 regulates cytoskeletal dynamics to promote tumor cell migration and invasion. RAC1, a Rho family GTPase, is an essential mediator of HDAC6 function, and is necessary and sufficient for RMS cell migration and invasion. High expression of RAC1 correlates with poor clinical prognosis in RMS patients. Targeting the HDAC6-RAC1 axis represents a promising therapeutic option for improving survival outcomes of RMS patients.

5.
J Physiol Biochem ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201407

RESUMO

Never in mitosis gene A-related kinase 2 (NEK2) has been recognized as an oncogene involved in the initiation and progression of various human cancers. However, our knowledge is still lacking in regard to the function of NEK2 in gastric cancer, the most common cancer in Eastern Asia associated with poor prognosis. Therefore, in the present study, we investigated the association of NEK2 with gastric cancer. We found that the development of gastric cancer is associated with NEK2 overexpression, particularly in patients with large tumor size and lymph node metastasis. We also provided evidence that NEK2 overexpression binds to and inhibits protein phosphatase 1 (PP1), which subsequently activates AKT and the downstream oncogenic pathways. As a result, via AKT/HIF1α axis, the glucose metabolism is reprogrammed towards aerobic glycolysis to provide rapid energy for the growth of gastric cancer cells. Moreover, the autophagic activity is suppressed via AKT/mTOR axis, leading to impaired response to cancer treatment and enhanced cell survival. In contrast, inactivating AKT by NEK2 silencing decreases aerobic glycolysis and promotes autophagic cell death, which eventually inhibits the growth of gastric cancer cell. All these results revealed that NEK2 promotes gastric cancer progression via activating AKT-mediated signaling pathways, which expanded our knowledge on gastric cancer pathogenesis and also provided novel target for clinical treatment.

6.
Lung Cancer ; 150: 164-171, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33186858

RESUMO

OBJECTIVES: Health-related quality of life (HRQoL) data complement conventional clinical endpoints when comparing adjuvant gefitinib with chemotherapy in patients with early-stage non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutations. This study aimed to assess changes in HRQoL with adjuvant gefitinib vs chemotherapy in this patient group. MATERIALS AND METHODS: In the phase III ADJUVANT trial, patients with completely resected, stage II-IIIA (N1-N2), EGFR-mutant NSCLC were randomized (1:1) to receive either gefitinib for 24 months or vinorelbine plus cisplatin (VP) every 3 weeks for four cycles. HRQoL was assessed as a secondary endpoint using the Functional Assessment of Cancer Therapy-Lung Cancer (FACT-L), Lung Cancer Symptom Scale (LCSS) questionnaires, and Trial Outcome Index (TOI) composite score. HRQoL dynamics, improvements, and time to deterioration were compared between groups. RESULTS: At baseline, 104 of 106, and 80 of 87 patients receiving gefitinib and VP, respectively, completed two questionnaires (FACT-L and LCSS). Baseline scores were balanced between groups. Although HRQoL fluctuated and gradually improved in both groups, longitudinally higher scores were reported with gefitinib than VP (FACT-L, odds ratio 418.16, 95 % confidence interval [CI] 2.75-63509.05, p =  0.019; LCSS, 1.13, 1.04-1.22, p =  0.003; TOI, 88.39, 4.40-1775.05, p =  0.003). Time to deterioration in HRQoL was delayed with gefitinib compared with VP (FACT-L, median 69 vs 6 weeks, hazard ratio 0.62, 95 % CI 0.42-0.90, p =  0.013; LCSS, median 45 vs 6 weeks, 0.63, 0.43-0.93, p =  0.020; TOI, median 164 vs 9 weeks, 0.51, 0.33-0.77, p =  0.001). CONCLUSION: Adjuvant gefitinib is associated with improved HRQoL over VP, supporting its use in patients with stage II-IIIA (N1-N2), EGFR-mutant NSCLC.

7.
Clin Nutr ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33131908

RESUMO

BACKGROUND & AIMS: Plasma ceramides have been identified as novel risk factors for metabolic and cardiovascular diseases. We aimed to evaluate the effects of dietary anthocyanins on plasma ceramides and to disentangle whether the alterations in ceramides could be related with those in other cardiometabolic risk factors in the dyslipidemia. METHODS: In a randomized double-blinded placebo-controlled trial, 176 eligible dyslipidemia subjects were randomly assigned into four groups receiving placebo, 40, 80, or 320 mg/day anthocyanins, respectively for 12 weeks. RESULTS: A total of 169 subjects completed the study. After 12-week intervention, dietary anthocyanins dose-dependently reduced plasma concentrations of all six ceramide species in the dyslipidemia subjects (all Ptrend values < 0.05). Specifically, 320 mg/day anthocyanins effectively lowered plasma N-palmitoylsphingosine (Cer 16:0, mean change: -28.3 ± 41.2 versus 2.9 ± 38.2, nmol/L, P = 0.018) and N-tetracosanoylsphingosine (Cer 24:0, mean change: -157.1 ± 493.9 versus 10.7 ± 439.9, nmol/L, P = 0.002) compared with the placebo. The declines in plasma Cer 16:0 and Cer 24:0 were significantly correlated with the decreases in plasma non-high-density lipoprotein cholesterol (nonHDL-C, Spearman's r = 0.32, P = 0.040 for Cer 16:0; Spearman's r = 0.35, P = 0.026 for Cer 24:0), apolipoprotein B (Spearman's r = 0.33, P = 0.031 for Cer 16:0; Spearman's r = 0.48, P = 0.002 for Cer 24:0), and total cholesterol (Spearman's r = 0.34, P = 0.026 for Cer 16:0; Spearman's r = 0.31, P = 0.042 for Cer 24:0) after 12-week 320 mg/day anthocyanin administration. Besides, we found that anthocyanins at 320 mg/day also markedly enhanced cholesterol efflux capacity in the dyslipidemia, the changes of which were positively associated with the reductions in Cer 16:0 (Spearman's r = 0.42, P = 0.006) independent of HDL-C and apolipoprotein A-I. CONCLUSIONS: Reductions in plasma Cer 16:0 and Cer 18:0 after 12-week anthocyanin intervention were dose-dependently associated with improvements in plasma lipids and cholesterol efflux capacity in the dyslipidemia. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov with the identifier No. NCT03415503.

8.
HPB (Oxford) ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33187828

RESUMO

BACKGROUND: This study aimed to investigate the prognostic impact of parenchyma-sparing hepatectomy (PSH) on solitary small intrahepatic cholangiocarcinoma (ICC). METHODS: A total of 184 patients with solitary small ICC (≤ 5 cm) from 2009 to 2017 were included. Short- and long-term outcomes were compared between PSH and Non-PSH approach. RESULTS: 95 (51.6%) patients underwent PSH and 89 (48.4%) patients underwent Non-PSH for solitary small ICC. PSH was associated with less intraoperative blood loss (212.9 mL versus 363.5 mL, P=0.038), lower transfusion rate (7.4% versus 16.9%, P=0.048), without increasing the frequency of tumor recurrence (60.0% versus 58.4%). No significant differences were observed in overall survival (OS), recurrence-free survival (RFS) and liver RFS (P = 0.627, 0.769 and 0.538, respectively). 109 (59.2%) patients experienced recurrence, of these, 67 (36.4%) were intrahepatic recurrence. Subgroup analysis of patients with liver-only recurrence demonstrated an increased likelihood of repeat hepatectomy for PSH compared to Non-PSH (21.2% versus 2.9%, P = 0.031), thus resulting in improved liver OS (P = 0.016). CONCLUSION: PSH was associated with improved perioperative outcomes but it did not increase liver recurrence rates. PSH offered an increased rate of salvage hepatectomy for recurrent tumor, thus improving long-term survival in cases in which liver recurrence occurred.

9.
Genes (Basel) ; 11(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158173

RESUMO

Metastasis and recurrence are the main causes of lung adenocarcinoma patients' death. Lymphatic metastasis is the main way of non-small cell lung cancer (NSCLC) metastasis. C-C chemokine receptor type 7 (CCR7) overexpression has been demonstrated to mediate occurrence and progression of NSCLC. Moreover, Chemokine ligand 21 (CCL21) was used to activate CCR7. The CCR7-CCL21 axis is one of the most common "chemokine-receptor" modes of action in the development and metastasis of multiple tumors. However, the role of the CCR7-CCL21 axis in lymphatic metastasis of NSCLC is poorly understood. The study was conducted to investigate the molecular mechanism underlying CCR7-CCL21 axis-mediated lymphatic metastasis of NSCLC A549 cells. Tumor necrosis factor α (TNF-α) could regulate the tumor microenvironment balance by promoting chemokine secretion. Our study demonstrated that TNF-α promoted CCL21 production in human lymphatic endothelial cells (HLEC). Results further showed that TNF-α significantly activated the NF-κB pathway in HLEC. NF-κB pathway inhibition with ammonium pyrrolidinedithiocarbamate (PDTC) caused a significant decrease in CCL21 secretion, suggesting that TNF-α-induced CCL21 secretion in HLEC was through NF-κB pathway. Co-culture of A549 cells and TNF-α-treated HLEC confirmed that the metastasis of A549 cells was enhanced, meanwhile, apoptosis-related proteins were hardly affected. The data proved that a co-culture system prevented cell apoptosis while inducing the lymphatic metastasis of A549 cells. However, the situation was reversed after neutralizing CCL21 expression, suggesting that TNF-α-induced CCL21 secretion in HLEC is involved in A549 cells metastasis. Collectively, our finding demonstrated that NF-κB pathway-controlled CCL21 secretion of HLEC contributing to the lymphatic metastasis of A549 cells via the CCR7-CCL21 axis, validating the CCR7-CCL21 axis as a potential target to inhibit metastasis of NSCLC.

10.
Cell Mol Life Sci ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170304

RESUMO

The efficacy of targeted therapy in non-small-cell lung cancer (NSCLC) has been impeded by various mechanisms of resistance. Besides the mutations in targeted oncogenes, reversible lineage plasticity has recently considered to play a role in the development of tyrosine kinase inhibitors (TKI) resistance in NSCLC. Lineage plasticity enables cells to transfer from one committed developmental pathway to another, and has been a trigger of tumor adaptation to adverse microenvironment conditions including exposure to various therapies. More importantly, besides somatic mutation, lineage plasticity has also been proposed as another source of intratumoural heterogeneity. Lineage plasticity can drive NSCLC cells to a new cell identity which no longer depends on the drug-targeted pathway. Histological transformation and epithelial-mesenchymal transition are two well-known pathways of lineage plasticity-mediated TKI resistance in NSCLC. In the last decade, increased re-biopsy practice upon disease recurrence has increased the recognition of lineage plasticity induced resistance in NSCLC and has improved our understanding of the underlying biology. Long non-coding RNAs (lncRNAs), the dark matter of the genome, are capable of regulating variant malignant processes of NSCLC like the invisible hands. Recent evidence suggests that lncRNAs are involved in TKI resistance in NSCLC, particularly in lineage plasticity-mediated resistance. In this review, we summarize the mechanisms of lncRNAs in regulating lineage plasticity and TKI resistance in NSCLC. We also discuss how understanding these themes can alter therapeutic strategies, including combination therapy approaches to overcome TKI resistance.

11.
Dent Traumatol ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222417

RESUMO

BACKGROUND/AIMS: Indirect pulp capping, pulpotomy and apexification are three common endodontic treatments for immature traumatized incisors. They all affect tooth root development to some extent. The aim of this retrospective study was to compare the influence of these treatments on root development of immature permanent incisors following dental trauma. MATERIALS AND METHODS: Twenty one indirect pulp capping, 48 pulpotomy, and 58 apexification cases with a mean age of 8.4±1.0 years and median follow-up of 12 months were included. NIH ImageJ with TurboReg plug-in was used to correct angular differences between the pre-operative and recall periapical radiographs, and to calculate variations of root length, dentin wall thickness and apical closure. Kruskal-Wallis ANOVA followed by pairwise comparisons were applied to compare the radiographic variations. The type of apical closure was assessed qualitatively and analyzed using Fisher's Exact Test. RESULTS: The apexification group had a lower trend towards apical closure than the other two groups (p<0.05). It also showed thinner dentin wall thickness compared with the pulpotomy group (p=0.001). There was no significant difference between pulpotomy and indirect pulp capping in the trend to apical closure (p>0.05) or dentin wall thickness (p=0.775). There was no significant difference in the variation of root length among the three groups (p=0.06). There was a moderate correlation between the treatment and the type of apical closure (Cramer's V Coefficient=0.375). Pulpotomy tended to form a normal apical constriction rather than a calcific barrier while apexification showed the opposite inclination. Indirect pulp capping had no specific inclination towards any type of apical closure. CONCLUSIONS: Apexification resulted in an abnormal root development mostly by affecting the dentin wall thickness and apical closure. Pulpotomy was beneficial for normal root development of immature traumatized teeth.

12.
Dalton Trans ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206738

RESUMO

In the past few decades, the construction of discrete supramolecular double-metallacycles has attracted wide interest because of their unique structures and their potential applications in photoelectric materials. Since some progress has been made in this area, it is time to summarize the progress of discrete supramolecular double-metallacycles. In this review, we will briefly introduce the synthetic strategy of discrete supramolecular double-metallacycles. In addition, we will discuss the design principles, preparation methods, optical properties, and functions of these discrete supramolecular double-metallacycles.

13.
Thorac Cancer ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205914

RESUMO

BACKGROUND: The majority of previous studies of the clinical outcome of video-assisted thoracoscopic surgery (VATS) versus open lobectomy for pathological N2 non-small cell lung cancer (pN2 NSCLC) have been single-center experiences with small patient numbers. The aim of this study was therefore to investigate these procedures but in a large cohort of Chinese patients with pathological N2 NSCLC in real-world conditions. METHODS: Patients who underwent lobectomy for pN2 NSCLC by either VATS or thoracotomy were retrospectively reviewed from 10 tertiary hospitals between January 2014 and September 2017. Perioperative outcomes and overall survival of the patients were analyzed. Cox regression analysis was performed to identify potential prognostic factors. Propensity-score analysis was performed to reduce cofounding biases and compare the clinical outcomes between both groups. RESULTS: Among 2144 pN2 NSCLC, 1244 patients were managed by VATS and 900 by open procedure. A total of 305 (24.5%) and 344 patients died during VATS and the thoracotomy group during a median follow-up of 16.7 and 15.6 months, respectively. VATS lobectomy patients had better overall survival when compared with those undergoing the open procedure (P < 0.0001). Multivariate COX regression analysis showed VATS lobectomy independently favored overall survival (HR = 0.75, 95% CI: 0.621-0.896, P = 0.0017). Better perioperative outcomes, including less blood loss, shorter drainage time and hospital stay, were also observed in patients undergoing VATS lobectomy (P < 0.05). After propensity-score matching, 169 patients in each group were analyzed, and no survival difference were found between the two groups. Less blood loss was observed in the VATS group, but there was a longer operation time. CONCLUSIONS: VATS lobectomy might be a feasible alternative to conventional open surgery for resectable pN2 NSCLC. KEY POINTS: Significant findings of the study: VATS lobectomy has comparative OS in pN2 NSCLC versus open procedure in resectable patients. WHAT THIS STUDY ADDS: VATS lobectomy might be feasible for pN2 NSCLC.

14.
Drug Test Anal ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33142047

RESUMO

Performing fast qualitative identification of seized illegal drugs by Raman spectroscopy is challenging due to fluorescence interference as well as chemical complexity. Spectrometers with 785-nm excitation, 1,064-nm excitation, and sequentially shifted excitation (SSE) were compared for their effect on fluorescence reduction. The characteristic peaks method, which is independent of cutting agents, was tested as a new strategy to broaden the application of the Raman technique. The suitability of the characteristic peaks method was fully examined by analyzing a large amount of seized illegal drugs, including 72 methamphetamine hydrochloride (concentration range of 13.9%-99.4%), 68 ketamine hydrochloride (17.7%-99.8%), 176 heroin hydrochloride (5.2%-79.5%), 51 cocaine hydrochloride (21.1%-94.5%), and 33 cocaine base (30.9%-92.5%) samples. The results showed that seized methamphetamine, ketamine, and cocaine samples had no or little fluorescence. Hence, in regard to detection of these samples, the advantage of using 1,064-nm excitation and SSE compared with 785-nm excitation was quite limited. Regarding the heroin samples, a significant improvement of the "high" confident positive detected rate was evident for 1,064 nm excitation (60.8%) and SSE (61.4%), compared with 785-nm excitation (13.1%). However, it was also seen that even if 1,064-nm excitation and SSE were applied, the fluorescence of heroin samples was still unable to be fully overcome. By using the characteristic peaks method, low LOD results of 5%-20% were acquired for 40 types of drug mixtures, and lower LODs were obtained for the 60% of the drug mixtures compared with library searching method. Raman spectroscopy in conjunction with the characteristic peaks method was shown to be fast, simple, accurate, and sensitive in the qualitative analysis of seized drug samples.

15.
Cell Rep ; 33(5): 108340, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33147459

RESUMO

Bioenergetic reprogramming during hypoxia adaption is critical to promote hepatocellular carcinoma (HCC) growth and progression. However, the mechanism underlying the orchestration of mitochondrial OXPHOS (oxidative phosphorylation) and glycolysis in hypoxia is not fully understood. Here, we report that mitochondrial UQCC3 (C11orf83) expression increases in hypoxia and correlates with the poor prognosis of HCC patients. Loss of UQCC3 impairs HCC cell proliferation in hypoxia in vitro and in vivo. Mechanistically, UQCC3 forms a positive feedback loop with mitochondrial reactive oxygen species (ROS) to sustain UQCC3 expression and ROS generation in hypoxic HCC cells and subsequently maintains mitochondrial structure and function and stabilizes HIF-1α expression to enhance glycolysis under hypoxia. Thus, UQCC3 plays an indispensable role for bioenergetic reprogramming of HCC cells during hypoxia adaption by simultaneously regulating OXPHOS and glycolysis. The positive feedback between UQCC3 and ROS indicates a self-modulating model within mitochondria that initiates the adaptation of HCC to hypoxic stress.

16.
J Clin Lab Anal ; : e23624, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33150661

RESUMO

INTRODUCTION: Human dental pulp stem cells (DPSCs) have potential applications in regenerative medicine. The molecular mechanisms underlying DPSCs viability and apoptosis are not completely understood. Here, we investigated the role of miR-126 in DPSCs viability and apoptosis. MATERIAL AND METHODS: Senescent DPSCs were compared with early passage DPSCs. real-time PCR and microARRAY were performed to identify the differential expression of miR-126, and western blot was performed to detect the expression of PTEN. MTT assay was utilized to reveal the proliferative rate of both senescent and early passage DPSCs. Flow cytometry was used to examine the apoptotic rate of DPSCs. Dual-luciferase reporter assay was carried out to detect the interaction of miR-126 and PTEN. RESULTS: Senescent DPSCs showed a high level of apoptosis. Further study showed that miR-126 is upregulated in senescent DPSCs and its overexpression in early passaged DPSCs induced apoptosis. Phosphatase and tensin homolog gene (PTEN) was identified as a target of miR-126. PTEN was downregulated in senescent DPSCs, whereas miR-126 inhibition upregulated PTEN level, and subsequently activated Akt pathway and suppressed the apoptotic phenotype of senescent DPSCs. In addition, PTEN overexpression rescued apoptosis of DPSCs at later stage. CONCLUSION: Our results demonstrate that the miR-126-PTEN-Akt axis plays a key role in the regulation of DPSCs apoptosis and provide a candidate target to improve the functional and therapeutic potential of DPSCs.

17.
IEEE Trans Cybern ; PP2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119525

RESUMO

Beyond generating long and topic-coherent paragraphs in traditional captioning tasks, the medical image report composition task poses more task-oriented challenges by requiring both the highly accurate medical term diagnosis and multiple heterogeneous forms of information, including impression and findings. Current methods often generate the most common sentences due to dataset bias for the individual case, regardless of whether the sentences properly capture key entities and relationships. Such limitations severely hinder their applicability and generalization capability in medical report composition, where the most critical sentences lie in the descriptions of abnormal diseases that are relatively rare. Moreover, some medical terms appearing in one report are often entangled with each other and co-occurred, for example, symptoms associated with a specific disease. To enforce the semantic consistency of medical terms to be incorporated into the final reports and encourage the sentence generation for rare abnormal descriptions, we propose a novel framework that unifies template retrieval and sentence generation to handle both common and rare abnormality while ensuring the semantic coherency among the detected medical terms. Specifically, our approach exploits hybrid-knowledge co-reasoning: 1) explicit relationships among all abnormal medical terms to induce the visual attention learning and topic representation encoding for better topic-oriented symptoms descriptions and 2) adaptive generation mode that changes between the template retrieval and sentence generation according to a contextual topic encoder. The experimental results on two medical report benchmarks demonstrate the superiority of the proposed framework in terms of both human and metrics evaluation.

18.
EBioMedicine ; 61: 103048, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33039712

RESUMO

BACKGROUND: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. METHOD: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. FINDINGS: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. INTERPRETATION: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. FUNDING: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).

19.
Environ Pollut ; 268(Pt B): 115733, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33011576

RESUMO

With numerous new chemicals introduced into the environment everyday, identification of their potential hazards to the environment and human health is a considerable challenge. Developing adverse outcome pathway (AOP) framework is promising in helping to achieve this goal as it can bring In Vitro testing into toxicity measurement and understanding. To explore the toxic mechanism underlying environmental chemicals via the AOP approach, an integration of adequate experimental data with systems biology understanding is preferred. Here, we describe a novel method to develop reliable and sensible AOPs that relies on chemical-gene interactions, toxicity pathways, molecular regulations, phenotypes, and outcomes information obtained from comparative toxicogenomics database (CTD) and Ingenuity Pathway Analysis (IPA). Using Benzo(a)pyrene (BaP), a highly studied chemical as a stressor, we identified the pivotal IPA toxicity pathways, the molecular initiating event (MIE), and candidate key events (KEs) to structure AOPs in the liver and lung, respectively. Further, we used the corresponding CTD information of multiple typical AHR-ligands, including 2,3,7,8-tetrachlorodibenzoparadioxin (TCDD), valproic acid, quercetin, and particulate matter, to validate our AOP networks. Our approach is likely to speed up AOP development as providing a time- and cost-efficient way to collect all fragmented bioinformation in published studies. It also facilitates a better understanding of the toxic mechanism of environmental chemicals, and potentially brings new insights into the screening of critical paths in the AOP network.

20.
Hepatology ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33125780

RESUMO

Increasing evidence in recent years has suggested that microRNA-7 (miR-7) is an important gene implicated in the development of various diseases including hepatocellular carcinoma. However, the role of miR-7 in autoimmune hepatitis (AIH) is unknown. Herein, we showed that miR-7 deficiency led to exacerbated pathology in ConA-induced murine acute autoimmune liver injury model (ALI), accompanied with hyperactivation state of CD4+ T cells. Depletion of CD4+ T cells reduced the effect of miR-7 deficiency on the pathology of ALI. Interestingly, miR-7 deficiency elevated CD4+ T cell activation, proliferation and cytokine production in vitro. Adoptive cell transfer experiments showed that miR-7def CD4+ T cells could exacerbate the pathology of ALI. Further analysis showed that miR-7 expression was upregulated in activated CD4+ T cells. Importantly, the transcription of pre-miR-7b, major resource of mature miR-7 in CD4+ T cells, was dominantly dependent on transcription factor C/EBPα which binding to core promoter region of miR-7b gene. Global gene analysis showed that MAPK4 was a new target of miR-7 in CD4+ T cells. Finally, the loss of MAPK4 could ameliorate the activation state of CD4+ T cells with or without miR-7 deficiency. Our studies are the first to document the important role of miR-7 in the setting of AIH induced by ConA. Specifically, we provide evidence that the C/EBPα/miR-7 axis negatively controls CD4+ T cell activation and function via MAPK4, thereby orchestrating experimental AIH in mice. Conclusion: These data expand on the important role of miR-7 in liver-related diseases and reveal the value of C/EBPα/miR-7 axis in CD4+ T cell biological function for the pathogenesis of immune-mediated liver diseases.

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