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1.
Biomed Chromatogr ; : e5140, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830528

RESUMO

Due to the complexity of the composition of herbal and dietary supplement (HDS), it is a challenging problem to efficiently screen and identify active or toxic compounds. Psoralea corylifolia L. (PCL) is selected as the object to establish a methodology for rapid screening and identification of hepatotoxic compounds. High-content imaging and ultra-performance liquid chromatography and high-resolution mass spectrometry were used in this study to detect the hepatotoxicity and identified unknown compounds in PCL samples. Then, putative toxic compounds which are highly related to hepatotoxicity were screened by spectrum-toxicity correlation analysis, and verified the toxicity intensity by high-content imaging. The maximum non-toxic dose of processed samples with good detoxification effect reduced more than 9 times compared to unprocessed raw medicinal materials. Spectrum-toxicity correlation analysis showed that bavachinin A, bavachin, isobavachalcone, and neobavaisoflavone had high correlation with hepatotoxicity of PCL, and psoralen and isopsoralen had low correlation with the hepatotoxicity. This study verified the hepatotoxicity of this six putative compound monomers, proving the results of spectrum-toxicity correlation analysis. Based on the correlation analysis of high-resolution mass spectrometry of detection compounds and high-content imaging hepatocyte toxicity data, the potential toxic compound of HDS products can be quickly and accurately screened.

2.
Brief Bioinform ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33822848

RESUMO

Irregular splicing was associated with tumor formation and progression in renal cell carcinoma (RCC) and many other cancers. By using splicing data in the TCGA SpliceSeq database, RCC subtype classification was performed and splicing features and their correlations with clinical course, genetic variants, splicing factors, pathways activation and immune heterogeneity were systemically analyzed. In this research, alternative splicing was found useful for classifying RCC subtypes. Splicing inefficiency with upregulated intron retention and cassette exon was associated with advanced conditions and unfavorable overall survival of patients with RCC. Splicing characteristics like splice site strength, guanine and cytosine content and exon length may be important factors disrupting splicing balance in RCC. Other than cis-acting and trans-acting regulation, alternative splicing also differed in races and tissue types and is also affected by mutation conditions, pathway settings and the response to environmental changes. Severe irregular splicing in tumor not only indicated terrible intra-cellular homeostasis, but also changed the activity of cancer-associated pathways by different splicing effects including isoforms switching and expression regulation. Moreover, irregular splicing and splicing-associated antigens were involved in immune reprograming and formation of immunosuppressive tumor microenvironment. Overall, we have described several clinical and molecular features in RCC splicing subtypes, which may be important for patient management and targeting treatment.

3.
ACS Nano ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33818068

RESUMO

Rich valleytronics and diverse defect-induced or interlayer pre-bandgap excitonics have been extensively studied in transition metal dichalcogenides (TMDCs), a system with fascinating optical physics. However, more intense high-energy absorption peaks (∼3 eV) above the bandgaps used to be long ignored and their underlying physical origin remains to be unveiled. Here, we employ momentum resolved electron energy loss spectroscopy to measure the dispersive behaviors of the valley excitons and intense higher-energy peaks at finite momenta. Combined with accurate Bethe-Salpeter equation calculations, non-band-nesting transitions at the Q valley and at the midpoint of KM are found to be responsible for the high-energy broad absorption peaks in tungsten dichalcogenides and present spin polarizations similar to A excitons, in contrast with the band-nesting mechanism in molybdenum dichalcogenides. Our experiment-theory joint research will offer insights into the physical origins and manipulation of the intense high-energy excitons in TMDC-based optoelectronic devices.

4.
Nat Commun ; 12(1): 2031, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795676

RESUMO

Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 184 experiments. We find and experimentally validate the extensive presence of murine viral sequence reads covering entire viral genomes in patient-derived xenografts. The existence of viral sequences inside tumor cells is further confirmed by single cell sequencing data. Extensive chimeric reads containing both viral and human sequences are also observed. Furthermore, we find significantly changed expression levels of many cancer-, immune-, and drug metabolism-related genes in samples with high virus load. Our analyses indicate a need to carefully evaluate the impact of viral infection on patient-derived xenografts for drug development. They also point to a need for attention to quality control of patient-derived xenograft experiments.

5.
Korean J Pain ; 34(2): 156-164, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33785667

RESUMO

Several types of pain occur following spinal cord injury (SCI); however, neuropathic pain (NP) is one of the most intractable. Invasive and non-invasive brain stimulation techniques have been studied in clinical trials to treat chronic NP following SCI. The evidence for invasive stimulation including motor cortex and deep brain stimulation via the use of implanted electrodes to reduce SCI-related NP remains limited, due to the small scale of existing studies. The lower risk of complications associated with non-invasive stimulation, including transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), provide potentially attractive alternative central neuromodulation techniques. Compared to rTMS, tDCS is technically easier to apply, more affordable, available, and potentially feasible for home use. Accordingly, several new studies have investigated the efficacy of tDCS to treat NP after SCI. In this review, articles relating to the mechanisms, clinical efficacy and safety of tDCS on SCI-related NP were searched from inception to December 2019. Six clinical trials, including five randomized placebo-controlled trials and one prospective controlled trial, were included for evidence specific to the efficacy of tDCS for treating SCI-related NP. The mechanisms of action of tDCS are complex and not fully understood. Several factors including stimulation parameters and individual patient characteristics may affect the efficacy of tDCS intervention. Current evidence to support the efficacy of utilizing tDCS for relieving chronic NP after SCI remains limited. Further strong evidence is needed to confirm the efficacy of tDCS intervention for treating SCI-related NP.

6.
Urolithiasis ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33786645

RESUMO

This study aimed to observe whether calcium oxalate (CaOx) crystals can induce the activation of endoplasmic reticulum (ER) stress in human renal cortex proximal tubule epithelial (HK-2) cells and to explore the regulatory of ER stress on the damage and apoptosis of HK-2 cells induced by CaOx crystals. We detected the optimal CaOx crystal concentration and intervention time by Western blot. ER stress modifiers tunicamycin (TM) and 4-phenylbutyric acid (4-PBA) were used to regulate the ER stress of HK-2 cells. The activities of ER stress marker proteins GRP78 and CHOP were evaluated by Western blot and immunohistochemistry. Western blot and TUNEL staining were used to detect cell apoptosis. We observed cell-crystal adhesion with an optical microscope. Lactate dehydrogenase (LDH) test kit and IL-1ß enzyme-linked immunosorbent assay kit were used to detect and evaluate HK-2 cell damage. We found that the expression of ER stress marker proteins GRP78 and CHOP gradually increased with the increase in CaOx crystal concentration and intervention time and reached the maximum at 2.0 mmol/L and 24 h. The use of ER stress modifiers TM and 4-PBA can effectively regulate the ER stress level induced by CaOx crystals, and the level of apoptosis is positively correlated with the level of ER stress. 4-PBA pretreatment remarkably reduced cell-crystal adhesion and the secretions of IL-1ß and LDH, whereas the results of TM pretreatment were the opposite. In summary, the damage and apoptosis of HK-2 cells induced by CaOx crystals are closely related to the level of ER stress. Inhibiting the ER stress of HK-2 cells can substantially reduce the cell damage and apoptosis induced by CaOx crystals.

7.
ChemMedChem ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780139

RESUMO

With the advantage of inherent responsiveness that can change the spectroscopic signals from "off" to "on" state in responding to targets (e.g. biological analytes/microenvironmental factors), activatable fluorescent probes have attracted extensive attention and made significant progress in the fields of bioimaging and biosensing. Due to the depth of tissue penetration, minimal tissue damage and negligible background signals at longer wavelengths, the development of second near-infrared window (NIR-II) fluorescent materials provides a new opportunity to develop activable fluorescent probes. Here, we summarize mainly NIR-II fluorophores (such as rare earth-doped nanoparticles, quantum dots, single-walled carbon nanotubes, small molecule dyes, conjugated polymers and gold nanoclusters), current role and development of activatable NIR-II fluorescent probes (AFPs) for biomedical applications including biosensing , bioimaging and therapeutic . The potential challenges and perspectives of AFPs in deep-tissue imaging and clinical application are also discussed.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33674830

RESUMO

The COVID-19 pandemic swept across the world rapidly, infecting millions of people. An efficient tool that can accurately recognize important clinical concepts of COVID-19 from free text in electronic health records (EHRs) will be valuable to accelerate COVID-19 clinical research. To this end, this study aims at adapting the existing CLAMP natural language processing tool to quickly build COVID-19 SignSym, which can extract COVID-19 signs/symptoms and their 8 attributes (body location, severity, temporal expression, subject, condition, uncertainty, negation, and course) from clinical text. The extracted information is also mapped to standard concepts in the Observational Medical Outcomes Partnership common data model. A hybrid approach of combining deep learning-based models, curated lexicons, and pattern-based rules was applied to quickly build the COVID-19 SignSym from CLAMP, with optimized performance. Our extensive evaluation using 3 external sites with clinical notes of COVID-19 patients, as well as the online medical dialogues of COVID-19, shows COVID-19 SignSym can achieve high performance across data sources. The workflow used for this study can be generalized to other use cases, where existing clinical natural language processing tools need to be customized for specific information needs within a short time. COVID-19 SignSym is freely accessible to the research community as a downloadable package (https://clamp.uth.edu/covid/nlp.php) and has been used by 16 healthcare organizations to support clinical research of COVID-19.

9.
Brief Bioinform ; 22(2): 800-811, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33757278

RESUMO

OBJECTIVE: This study aims at reviewing novel coronavirus disease (COVID-19) datasets extracted from PubMed Central articles, thus providing quantitative analysis to answer questions related to dataset contents, accessibility and citations. METHODS: We downloaded COVID-19-related full-text articles published until 31 May 2020 from PubMed Central. Dataset URL links mentioned in full-text articles were extracted, and each dataset was manually reviewed to provide information on 10 variables: (1) type of the dataset, (2) geographic region where the data were collected, (3) whether the dataset was immediately downloadable, (4) format of the dataset files, (5) where the dataset was hosted, (6) whether the dataset was updated regularly, (7) the type of license used, (8) whether the metadata were explicitly provided, (9) whether there was a PubMed Central paper describing the dataset and (10) the number of times the dataset was cited by PubMed Central articles. Descriptive statistics about these seven variables were reported for all extracted datasets. RESULTS: We found that 28.5% of 12 324 COVID-19 full-text articles in PubMed Central provided at least one dataset link. In total, 128 unique dataset links were mentioned in 12 324 COVID-19 full text articles in PubMed Central. Further analysis showed that epidemiological datasets accounted for the largest portion (53.9%) in the dataset collection, and most datasets (84.4%) were available for immediate download. GitHub was the most popular repository for hosting COVID-19 datasets. CSV, XLSX and JSON were the most popular data formats. Additionally, citation patterns of COVID-19 datasets varied depending on specific datasets. CONCLUSION: PubMed Central articles are an important source of COVID-19 datasets, but there is significant heterogeneity in the way these datasets are mentioned, shared, updated and cited.

10.
Gastroenterology ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684427

RESUMO

BACKGROUND & AIMS: Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis. METHODS: Stool samples were collected from 118 hospital patients, divided into 3 groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28), and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed. RESULTS: Significant differences were observed in alpha and beta diversity between patients with CDI and Carrier (P < .05). Differential abundance analysis identified 2 genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in patients with CDI than in Carrier. Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier. CONCLUSIONS: Our study provides specific markers of stool fungi combined with host immune factors to distinguish patients with CDI from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted.

11.
BMC Med Educ ; 21(1): 183, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766012

RESUMO

BACKGROUND: The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. METHOD: This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students' choices of psychiatry at matriculation and as a career. RESULTS: 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87-2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28-3.08), being female (OR = 1.50, 95% CI = 1.30-1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28-1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08-1.46) correlated positively with students' choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29-0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63-0.97) were less likely to choose psychiatry as a career. CONCLUSION: More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students' interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students' attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

12.
Nat Prod Res ; : 1-7, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764238

RESUMO

Four unsaturated fatty acid derivatives including three new pantheric acids (1-3), together with three known polyketides (5-7), were isolated from a culture broth of the marine-derived fungus Aspergillus sp. SCAU150. Their complete structures were determined by NMR and HRESIMS data analyses. The antifungal activity of the isolated compounds above was evaluated and 2 was found to show moderated activity toward the phytopathogenic fungus Fusarium solani bio-80814 with an inhibition zone diameter of 6 mm under 5 µg/disc.

13.
Chin J Nat Med ; 19(3): 225-230, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33781456

RESUMO

The phytochemical investigation of the stems of Homalium stenophyllum afforded seven new phenolic glycosides (1-5 and 8-9) and two known compounds (6 and 7). Their structures were elucidated by comprehensive analyses of NMR spectroscopic, mass spectrometric data and chemical hydrolysis. Additionally, their anti-inflammatory activities against the NO production in LPS-induced macrophages were evaluated.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33647938

RESUMO

OBJECTIVE: Automated analysis of vaccine postmarketing surveillance narrative reports is important to understand the progression of rare but severe vaccine adverse events (AEs). This study implemented and evaluated state-of-the-art deep learning algorithms for named entity recognition to extract nervous system disorder-related events from vaccine safety reports. MATERIALS AND METHODS: We collected Guillain-Barré syndrome (GBS) related influenza vaccine safety reports from the Vaccine Adverse Event Reporting System (VAERS) from 1990 to 2016. VAERS reports were selected and manually annotated with major entities related to nervous system disorders, including, investigation, nervous_AE, other_AE, procedure, social_circumstance, and temporal_expression. A variety of conventional machine learning and deep learning algorithms were then evaluated for the extraction of the above entities. We further pretrained domain-specific BERT (Bidirectional Encoder Representations from Transformers) using VAERS reports (VAERS BERT) and compared its performance with existing models. RESULTS AND CONCLUSIONS: Ninety-one VAERS reports were annotated, resulting in 2512 entities. The corpus was made publicly available to promote community efforts on vaccine AEs identification. Deep learning-based methods (eg, bi-long short-term memory and BERT models) outperformed conventional machine learning-based methods (ie, conditional random fields with extensive features). The BioBERT large model achieved the highest exact match F-1 scores on nervous_AE, procedure, social_circumstance, and temporal_expression; while VAERS BERT large models achieved the highest exact match F-1 scores on investigation and other_AE. An ensemble of these 2 models achieved the highest exact match microaveraged F-1 score at 0.6802 and the second highest lenient match microaveraged F-1 score at 0.8078 among peer models.

15.
Ital J Pediatr ; 47(1): 49, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663540

RESUMO

BACKGROUND: Phelan-McDermid syndrome (PMS), also known as 22q13.3 deletion syndrome, is a rare neurodevelopmental syndrome resulting from a deletion of the distal long arm of chromosome 22. CASE PRESENTATION: We report a case of a 21 months old Chinese girl presenting with global developmental delay, regression of language skills, unable to understand a few words or walk independently, insomnia, and autism-like behaviors. Copy number variation (CNV) analysis showed a heterozygous loss of SHANK3 gene in the 22q13 region, consistent with a diagnosis of PMS. After treatment with recombinant human growth hormone (rhGH), this patient had an improvement in motor skills and social behaviors. No side effects from rhGH therapy were reported. CONCLUSIONS: This is the first report of using rhGH to treat a Chinese girl diagnosed with PMS. We speculate rhGH could be a reasonable alternative choice for PMS treatment with similar clinical outcomes in comparison to insulin-like growth factor-1(IGF-1). However, further clinical trials are needed to confirm this hypothesis.

16.
J Gastroenterol ; 56(4): 395-405, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33742253

RESUMO

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. METHODS: We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. RESULTS: PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P < 0.001, and P < 0.001, respectively). Using these factors, we established a novel risk factor panel (R-panel), which predicted early recurrence (P < 0.001, HR = 15.02, 95% CI 5.76-39.19). Predictive accuracy of this R-panel was favorable, with a C-index of 0.853, higher than AJCC TNM staging (0.713). We further built an integrated staging system combining R-panel scoring and TNM staging, which improved predictive probability of TNM staging. Finally, we showed that adjuvant therapy with long-acting somatostatin analogs (SSAs) significantly reduced postoperative recurrence (P < 0.001) and prolonged long-term survival (P = 0.021) in patients with the above risk factors. CONCLUSION: We identified a novel risk factor panel, which includes PanNET G3, pancreatic duct dilatation, and perineural invasion; this panel predicted early recurrence of PanNETs after curative resection. Patients with these risk factors can benefit from adjuvant therapy with SSAs.

17.
Eur J Radiol ; 137: 109590, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33607372

RESUMO

PURPOSE: Acutely infarcted native T1 (native T1AI) and extracellular volume (ECVAI) could quantify myocardial injury after acute myocardial infarction (AMI). Therefore, we sought to further explore their association with left ventricular (LV) remodeling during follow-up. METHODS: 56 ST-segment-elevation MI patients were prospectively recruited and completed acute and 3-month cardiac magnetic resonance scans. T1 mapping, late gadolinium enhancement and cine imaging were performed to measure native T1AI, ECVAI, infarct size and LV global function, respectively. LV remodeling was evaluated as the change in LV end-diastolic volume index (△EDV) at follow-up scan compared with baseline. RESULTS: In acute scan, 37 patients (66.07 %) had microvascular obstruction (MVO). The native T1AI did not significantly differ between patients with or without MVO (1482.0 ±â€¯80.6 ms vs. 1469.0 ±â€¯71.6 ms, P =  0.541). However, ECVAI in patients without MVO was lower than that in patients with MVO (49.60 ±â€¯8.57 % vs. 58.53 ±â€¯8.62 %, P = 0.001). The native T1AI only correlated with △EDV in patients without MVO (rmvo- = 0.495, P = 0.031); while ECVAI was associated with △EDV in all patients (rmvo- = 0.665, P =  0.002; rmvo+ = 0.506, P =  0.001; rall patients = 0.570, P <  0.001). Furthermore, ECVAI was independently associated with LV remodeling in multivariable linear regression analysis (ß = 0.490, P =  0.002). CONCLUSION: As a promising parameter for early risk stratification after AMI, ECVAI is associated with LV remodeling during follow-up; while native T1AI may be feasible when MVO is absent.

18.
Cancer Commun (Lond) ; 41(4): 316-332, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33591636

RESUMO

BACKGROUND: Increased hypoxia-inducible factor 2α (HIF2α) activation is a common event in clear cell renal cell carcinoma (ccRCC) progression. However, the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated. We conducted this study to access the potential link between junction plakoglobin (JUP) and HIF2α in ccRCC. METHODS: Affinity purification and mass spectrometry (AP-MS) screening, glutathione-s-transferase (GST) pull-down and co-immunoprecipitation (Co-IP) assays were performed to detect the interacting proteins of HIF2α. Quantitative PCR (qPCR) and Western blotting were used to detect the expression of JUP in human ccRCC samples. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), cycloheximide chase assays, and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α. Cell Counting Kit-8 (CCK-8) assays, colony formation assays, transwell assays, and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells. RESULTS: We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau (VHL) and histone deacetylases 1/2 (HDAC1/2) to HIF2α to regulate its stability and transactivation. JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo. Importantly, the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes. CONCLUSION: Taken together, these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.

19.
JCI Insight ; 6(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33591953

RESUMO

One of the most common malignancies affecting adults with Neurofibromatosis type 1 (NF1) is the malignant peripheral nerve sheath tumor (MPNST), an aggressive and often fatal sarcoma that commonly arises from benign plexiform neurofibromas. Despite advances in our understanding of MPNST pathobiology, there are few effective therapeutic options, and no investigational agents have proven successful in clinical trials. To further understand the genomic heterogeneity of MPNST, and to generate a preclinical platform that encompasses this heterogeneity, we developed a collection of NF1-MPNST patient-derived xenografts (PDX). These PDX were compared with the primary tumors from which they were derived using copy number analysis, whole exome sequencing, and RNA sequencing. We identified chromosome 8 gain as a recurrent genomic event in MPNST and validated its occurrence by FISH in the PDX and parental tumors, in a validation cohort, and by single-cell sequencing in the PDX. Finally, we show that chromosome 8 gain is associated with inferior overall survival in soft-tissue sarcomas. These data suggest that chromosome 8 gain is a critical event in MPNST pathogenesis and may account for the aggressive nature and poor outcomes in this sarcoma subtype.

20.
Eur Radiol ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33638020

RESUMO

OBJECTIVE: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. METHODS: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. RESULTS: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05). CONCLUSIONS: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.

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