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1.
J Pharmacol Exp Ther ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820830

RESUMO

Obesity is dramatically increasing worldwide. Ginsenosides extracted from ginseng have been reported against obesity and the associated metabolic disorders. As a subtype of ginsenoside, ginsenoside Ro is a critical constituent of ginseng. However, its specific effects on obesity remains unknown. G protein-coupled bile acid receptor 5 (TGR5, also known as GPBAR1) is a bile acid membrane receptor, widely expressed in human tissues contributing to various metabolic processes to confer the regulations of glucose and lipid homeostasis.TGR5 has displayed potentials as a therapeutic target for the treatment of metabolic disorders. Here, we explore the anti-obesity effect of ginsenoside Ro with TGR5 activation screened by a library of natural products. Our results showed that the ginsenoside Ro (90mg/kg) treatment ameliorated body weight and lipid accumulation in multiple metabolic organs of high fat diet-induced obese (DIO) mice without affecting food intake, and improved oral glucose tolerance tests (OGTT), intraperitoneal insulin tolerance tests (IPITT), and fasting serum glucose. We also found that triglyceride (TG) and total cholesterol (TC) in serum and liver were significantly decreased after ginsenoside Ro treatment. Then we used Tgr5 knockout mice to explore the role of Tgr5 in the anti-obesity effect of ginsenoside Ro.Our results further demonstrated that ginsenoside Ro promoted glucagon-like peptide-1 (GLP-1) secretion and energy expenditure in wild type DIO mice. However, the stimulation of ginsenoside Ro on GLP-1 secretion and energy expenditure were restrained in the Tgr5 knockout mice.In conclusion, our findings demonstrated that ginsenoside Ro ameliorates obesity and insulin resistance in DIO mice via activating TGR5. Significance Statement Obesityis dramatically increasing worldwide and it contributes to multiple metabolic diseases. TGR5 is a potential therapeutic target for the treatment of metabolic disorders. Ginsenoside Ro, as aoleanane-type ginsenoside, ameliorates obesity and insulin resistance, promotes GLP-1 secretion, increases energy expenditure via activating TGR5. Ginsenoside Ro could be a potential leading compound for treating obesity and its associated metabolic diseases.

2.
Toxicon ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33836178

RESUMO

Methicillin-resistant staphylococci have become growing threats to human health, and novel antimicrobials are urgently needed. Natural antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics. Here, two novel cationic α-helical antimicrobial peptides, Lausporin-1 and Lausporin-2, were identified from the venom gland of the scorpion L. australasiae through a cDNA library screening strategy. Biochemical analyses demonstrated that Lausporin-1 and Lausporin-2 are cationic α-helical amphipathic molecules. Antimicrobial assays demonstrated that the two peptides possess antibacterial activities against several species of antibiotic-resistant staphylococci. Importantly, they are active against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus capitis, with the minimum inhibitory concentrations ranging from 2.5 to 10 µg/ml. Moreover, both peptides can induce dose-dependent plasma membrane disruptions of the bacteria. In short, our work expands the knowledge of the scorpion L. australasiae venom-derived AMPs and sheds light on the potential of Lausporin-1 and Lausporin-2 in the development of novel drugs against methicillin-resistant staphylococci.

3.
J Crit Care ; 64: 68-73, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33794469

RESUMO

Hypoglycemic episodes are associated with worse hospital outcomes. All adult patients admitted to our burn center from 2015 to 2019 were retrospectively reviewed. Patient demographics and burn characteristics were recorded. The primary outcome was mortality, and secondary outcomes were total length-of-stay and intensive care unit length-of-stay. All patients experiencing at least one hypoglycemic episode were compared to patients who did not experience hypoglycemia. There were 914 patients with acute burns admitted during the study period, 33 of which (4%) experienced hypoglycemic episodes. Of these, 17 patients (52%) experienced a single hypoglycemic episode, while the remainder experienced multiple hypoglycemic episodes. Patients with one or more hypoglycemic events were matched to non-hypoglycemic controls using propensity matching. Patients that experienced hypoglycemia had significantly less TBSA involvement (5% vs. 13%,median, p < 0.0002), higher prevalence of diabetes (48% vs. 18%, p < 0.0001), higher mortality (18% vs. 7%, p = 0.01), longer total length-of-stay (22 vs. 8 days, median, p < 0.0001), and longer ICU length-of-stay (12 vs. 0 days, median, p < 0.0001). A single hypoglycemic episode was associated with prolonged total (IRR = 1.91, p < 0.0001) and ICU length-of-stay (IRR = 3.86, p < 0.0001). Hypoglycemia was not associated with higher mortality in the survival analysis (p = 0.46).

4.
Nat Commun ; 12(1): 2203, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850133

RESUMO

Reactive oxygen species (ROS) are generated and consumed in living organism for normal metabolism. Paradoxically, the overproduction and/or mismanagement of ROS have been involved in pathogenesis and progression of various human diseases. Here, we reported a two-dimensional (2D) vanadium carbide (V2C) MXene nanoenzyme (MXenzyme) that can mimic up to six naturally-occurring enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione peroxidase (GPx), thiol peroxidase (TPx) and haloperoxidase (HPO). Based on these enzyme-mimicking properties, the constructed 2D V2C MXenzyme not only possesses high biocompatibility but also exhibits robust in vitro cytoprotection against oxidative stress. Importantly, 2D V2C MXenzyme rebuilds the redox homeostasis without perturbing the endogenous antioxidant status and relieves ROS-induced damage with benign in vivo therapeutic effects, as demonstrated in both inflammation and neurodegeneration animal models. These findings open an avenue to enable the use of MXenzyme as a remedial nanoplatform to treat ROS-mediated inflammatory and neurodegenerative diseases.

5.
J Med Chem ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33851529

RESUMO

Considering the nonideal metabolic stability of the difluoro-biphenyl-diarylpyrimidine lead compound 4, a series of novel alkylated difluoro-biphenyl-diarylpyrimidines were designed and synthesized based on their structure. Introducing alkyl or substituted alkyl groups on the linker region to block the potential metabolic sensitive sites generated 22 derivatives. Among them, compound 12a with an N-methyl group displayed excellent anti-HIV-1 activity and selectivity. The methyl group was hopped to the central pyrimidine to occupy the small linker region and maintain the water-mediated hydrogen bond observed in the binding of compound 4 with RT. The resulting compound 16y exhibited an improved anti-HIV-1 activity, much lower cytotoxicity, and nanomolar activity toward multiple mutants. In addition, 16y has a better stability in human liver microsomes than 4. Moreover, no apparent in vivo acute toxicity was observed in 16y-treated female, especially pregnant mice. This series of alkylated compounds with highly potency and safety represent a promising lead template for future discovery.

6.
Rev Cardiovasc Med ; 22(1): 231-238, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33792267

RESUMO

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.

7.
Pac Symp Biocomput ; 26: 172-183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33691015

RESUMO

Concurrently available genomic and transcriptomic data from large cohorts provide opportunities to discover expression quantitative trait loci (eQTLs)-genetic variants associated with gene expression changes. However, the statistical power of detecting rare variant eQTLs is often limited and most existing eQTL tools are not compatible with sequence variant file formats. We have developed AeQTL (Aggregated eQTL), a software tool that performs eQTL analysis on variants aggregated according to user-specified regions and is designed to accommodate standard genomic files. AeQTL consistently yielded similar or higher powers for identifying rare variant eQTLs than single-variant tests. Using AeQTL, we discovered that aggregated rare germline truncations in cis exomic regions are significantly associated with the expression of BRCA1 and SLC25A39 in breast tumors. In a somatic mutation pan-cancer analysis, aggregated mutations of those predicted to be missense versus truncations were differentially associated with gene expressions of cancer drivers, and somatic truncation eQTLs were further identified as a new multi-omic classifier of oncogenes versus tumor-suppressor genes. AeQTL is easy to use and customize, allowing a broad application for discovering rare variants, including coding and noncoding variants, associated with gene expression. AeQTL is implemented in Python and the source code is freely available at https://github.com/Huan-glab/AeQTL under the MIT license.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33750031

RESUMO

The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation-induced skeletal stem cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCs in vitro and in vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCs in vitro after irradiation were investigated. Mechanistically, the changes in tissue regeneration-associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a- and CD105-positive cells in skeletal tissues and mouse-derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA-Seq results showed that tissue regeneration-associated gene expression decreased, and the Western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation-induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC-mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC-mediated tissue regeneration postradiation.

9.
J Sep Sci ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646632

RESUMO

In this work, a new quantitative analysis method of multi-components analysis via a single marker strategy coupled with high-performance liquid chromatography (HPLC) analysis, was proposed to analyze nine nucleosides (cytidine, uridine, 2'-deoxyuridine, inosine, guanosine, 2'-deoxyguanosine, thymidine, adenosine, and 2'-deoxyadenosine) as quality control markers in Rhizoma Paridis. Guanosine was set as the internal reference substance, whose content in Rhizoma Paridis was determined using conventional external standard method. Then, relative correction factors between guanosine and the other eight nucleosides were measured respectively. The amounts of the other eight components were calculated according to the relative correction factors by the quantitative analysis of multi-components via a single marker method. Finally, the result of vector angle cosine analysis showed that there was no significant difference of the contents between the external standard method and the quantitative analysis of multi-components via a single marker method, indicating that the quantitative analysis of multi-components via a single marker method can be applied for the quality control of Rhizoma Paridis. As far as we know, this is also the first report to analyze nucleosides by the quantitative analysis of multi-components via a single marker method, providing an efficient and promising quality assessment method for other traditional Chinese medicine containing nucleosides.

10.
J Vasc Surg ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684468

RESUMO

OBJECTIVE: Endovascular abdominal aortic repair can involve the incorporation of renal arteries. Revascularization after intentional or unintentional renal artery (RA) coverage is not always technically successful, and the loss of a single RA may result in the need for postoperative dialysis. Thus, we compared the outcomes after endovascular aneurysm repair (EVAR) stratified by RA involvement (RAI). METHODS: Patient data from the Vascular Quality Initiative from 2009 to 2018 registry were analyzed. The exclusion criteria were preoperative dialysis, missing RAI data, and repair above the superior mesenteric artery. The repair type cohorts were defined as (1) no RAI (NRAI), (2) RAI with revascularization (RAI-R), and (3) RAI with no revascularization (RAI-NR). A sensitivity analysis was performed by excluding ruptured presentations. The primary outcome was the need for postoperative dialysis. The secondary outcomes were 30-day mortality, dialysis at follow-up, postoperative renal function, and 2-year survival. Multivariate analysis was used to determine the independent predictors for postoperative dialysis. The 2-year survival analysis was performed using Kaplan-Meier log-rank test. RESULTS: Of 54,020 patients in the EVAR and TEVAR (thoracic EVAR)/complex EVAR modules in the Vascular Quality Initiative, 25,724 met the criteria for inclusion (NRAI, n = 24,879; RAI-R, n = 733; RAI-NR, n = 112). The demographics and comorbidities were similar among the three groups. The RAI-NR group had more frequently had ruptured or symptomatic aneurysms. The postoperative dialysis requirement was higher in the RAI-NR group (NRAI, 0.7%; RAI-R, 2.2%; RAI-NR, 17%; P < .0001), as were the 30-day mortality and dialysis requirement at follow-up. On multivariate analysis, RAI-R (odds ratio [OR], 2.2; P = .03) and RAI-NR (OR, 5.9; P < .0001) were independent predictors of postoperative dialysis and remained so after excluding ruptured presentations (RAI-R: OR, 3; P = .003; RAI-NR: OR, 22.3; P < .0001). Other independent predictors of the need for postoperative dialysis were worse preoperative renal function, a symptomatic presentation, any preoperative or intraoperative blood transfusion, and larger blood loss (≥200 mL). Excluding those with rupture, the overall survival at 2 years on Kaplan-Meier analysis was lower for the RAI-NR group (NRAI, 92%; RAI-R, 89%; RAI-NR, 80%; P = .004). CONCLUSIONS: RAI is highly predictive of the need for postoperative and permanent dialysis after EVAR. RAI-NR was associated with lower overall survival. These risks should be considered when planning and performing EVAR and should be weighed against the risks of open repair when considering the treatment options.

11.
Medicine (Baltimore) ; 100(13): e25407, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787650

RESUMO

ABSTRACT: The Griffiths Mental Development Scale-Chinese (GDS-C) is used in China to assess the development of children from birth to 8 years of age. Language disorders are a common symptom of autism spectrum disorder (ASD) and global developmental delay (GDD)/intellectual disability (ID). There is a need to identify distinct clinical characteristics in children suspected of having these 2 disorders, mainly presenting as language disorders. Here, we aimed to use the GDS-C to evaluate children presenting with language problems to identify characteristics that distinguish ASD and GDD/ID. Children with language problems were recruited between August 2018 and December 2019. A total of 150 children aged 25 to 95.2 months were enrolled (50 in the ASD group, 50 in the GDD/ID group, and 50 in the typical group). Each group was subdivided by age as follows: 24-36 months, >36-60 months, and >60-96 months. Developmental characteristics assessed using the GDS-C were analyzed and compared. Both, children with ASD and GDD/ID presented with a lower developmental level than typical children in all six subscales of the GDS-C. No significant differences were observed in the six subscale scores between the ASD and GDD/ID groups, except for the practical reasoning subscale score in the >36 to 60 months subgroups, which was significantly lower in the GDD/ID group than in the ASD group. The developmental imbalance of subscales within the ASD and GDD/ID groups identified troughs in the personal-social, language, and practical reasoning areas in children with ASD and in the language and practical reasoning areas in children with GDD/ID relative to typical children. The GDS-C is a useful, comprehensive tool for the assessment of the developmental state of children with ASD and GDD/ID. Characteristics of practical reasoning subscale help diagnose autism in >36 to 60 months old children.

12.
DNA Cell Biol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781092

RESUMO

The abnormal proliferation of vascular smooth muscle cells (VSMCs) is crucial in the atherosclerosis. Although long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their roles in activation of VSMCs proliferation and vascular disorder diseases are not well understood. In addition, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) was reported to participate in lncRNAs-mediated function. Herein, we propose to investigate the role of lncRNA AC105942.1 and hnRNPA2/B1 in pathological VSMCs proliferation and the possible mechanisms in vitro. We have identified that lncRNA AC105942.1 was downregulated and hnRNPA2/B1 was upregulated in atherosclerotic plaques compared with normal artery tissues. Enhanced lncRNA AC105942.1 could noticeably inhibit Ang II-induced VSMCs proliferation. Further investigation suggested that lncRNA AC105942.1 could downregulate the expression of hnRNPA2/B1 and then regulate the level of CDK4 and p27. Taken together, our study indicated that lncRNA AC105942.1 downregulated hnRNPA2B1 to protect against the atherosclerosis by suppressing VSMCs proliferation. LncRNA AC105942.1 and hnRNPA2/B1 could represent potential therapeutic and diagnostic targets to atherosclerosis-related diseases.

13.
Rheumatol Ther ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666893

RESUMO

INTRODUCTION: The objective of this study is to identify the potential risk factors for progression from subclinical to clinical psoriatic arthritis (PsA). METHODS: A retrospective, longitudinal, case-control study was conducted at a single hospital, including 25 patients with clinically confirmed PsA in the case group and 137 controls without confirmed PsA. All patients in both groups had a medical history of subclinical PsA. Various baseline covariates were collected from all patients when they had a status of subclinical PsA. Univariate, multivariate, stratified, and interaction analyses were employed to identify potential risk factors of transiting to clinical PsA from subclinical PsA. RESULTS: In multivariate logistic regression analysis, older age (OR 10.15, 95% CI 2.79-36.91, p = 0.00), alcohol drinking (OR 3.43, 95% CI 1.17-10.12, p = 0.03), elevated high-sensitivity C-reactive protein (hs-CRP) (OR 1.05, 95% CI 1.01-1.09, p = 0.03) were identified as risk factors for transition from subclinical to clinical PsA. Stratified and logistic regression analyses suggest a significant interaction between age and fatty liver. For patients aged less than 45 years old, the association between fatty liver and clinical PsA was statistically significant. CONCLUSIONS: Older age, alcohol drinking, elevated hs-CRP, and the presence of fatty liver at less than 45 years old appear to increase the risk of transition from subclinical to clinical PsA. These findings call for a need to manage these risk factors.

14.
BMC Surg ; 21(1): 111, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658035

RESUMO

BACKGROUND: Gastrointestinal stromal tumor (GIST) can arise anyplace along the gastrointestinal (GI) tract. The uncommon tumor location in groin area is rarely reported. CASE PRESENTATION: We herein reported a metastasized case presented as GI hemorrhage complicated with indirect hernia, and underwent tumor cytoreduction, herniorrhaphy and chemotherapy for jejunal GIST. The case was described consecutively based on the process of surgical management, with a good follow-up result. A literature review by searching similar case reports from two national medical databases was performed to summarize clinical features of such unusual presentation of GIST, which included hernia characteristics, short- and long-term outcomes of this disease. It showed GIST presenting as groin hernia was rarely reported and all available 11 cases suggested a primary tumor and required both tumor resection and hernia repair. The long-term results indicated 64.3% overall survival at 5 years after the incidental diagnosis. CONCLUSIONS: Inguinal hernia is an extremely rare presentation of GIST, with limited case reports available in the literature. A radical involving tumor resection plus hernia repair is an optimal surgical approach for such uncommon condition. An adjuvant medication mounting on mutated KIT gene should be strictly followed for high risk cases.


Assuntos
Tumores do Estroma Gastrointestinal , Hérnia Inguinal , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Hérnia Inguinal/complicações , Hérnia Inguinal/cirurgia , Humanos
15.
Andrologia ; : e14039, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33682169

RESUMO

To assess the diagnostic value of shear wave elastography (SWE) for evaluating the histological spermatogenic function of azoospermic males, 91 patients with azoospermia who underwent standardised greyscale ultrasound and SWE examinations followed by testicular biopsy were retrospectively recruited. Spermatogenic function was classified by biopsy as normal testicular spermatogenesis (n = 61), hypospermatogenesis (n = 18), spermatogenesis arrest (n = 6) and Sertoli cell-only syndrome (n = 6). Significant differences in testicular size and SWE values were observed between these 4 groups (p < .01). The mean SWE value had good discrimination power (AUC = 0.79) with a cut-off value of 1.55 KPa, a sensitivity of 0.58, specificity of 0.85, positive predictive value (PPV) of 0.36 and negative predictive value (NPV) of 0.93. Testicular volume had an AUC of 0.75. With a cut-off value of 8.41 ml, the testicular volume had a sensitivity of 0.58, specificity of 0.92, PPV of 0.54 and NPV of 0.93. The mean SWE value and testicular volume efficiently discriminated patients with normal spermatogenesis and hypospermatogenesis from patients with Sertoli cell-only syndrome and spermatogenesis arrest.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33689273

RESUMO

At small scales, shape-programmable magnetic materials and self-sensing conductive materials have an enticing potential for realizing the functionalities that are unattainable by traditional machines. This work reports a facile preparation method of aself-sensing magnetism-responsive anisotropic films (SMAF) in which magnetic materials and conductive materials can be predesigned, oriented, and patterned without requiring an external magnetic field generator or other expensive devices. A variety of shaped magnetoactive films with complex chain-orientation structures that can achieve advanced actuation functions have been developed, such as magnetically driven flowers, windmills, and leaves. It is also verified that the as-prepared samples coated with the sensing layer can distinguish different actuation modes, such as inward bending, outward bending, twisting, and combined deformation, which would be conducive to further exploration and development of directionally responsive applications in the smart actuating system and soft robotics.

17.
J Agric Food Chem ; 69(10): 2965-2978, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33667087

RESUMO

Sclerotinia stem rot (SSR) of rapeseed (Brassica napus), caused by the soil-borne fungus Sclerotinia sclerotiorum, is one of the main diseases seriously affecting the yield and oil quality of infected rapeseed crops. The complexity of the inheritance of resistance and of the interaction mechanisms between rapeseed and S. sclerotiorum limits resistance gene identification and molecular breeding. In this review, the latest progress of research into resistance to SSR in B. napus is summarized from the following three directions: the pathogenesis mechanisms of S. sclerotiorum, the resistance mechanisms of B. napus toward S. sclerotiorum, and rapeseed breeding for resistance to SSR. This review aims to provide a theoretical basis and useful reference for analyzing the mechanism of the interaction between B. napus and S. sclerotiorum, searching for gene loci associated with the resistance response, and for achieving disease-resistance genetic manipulation and molecular design breeding in rapeseed.

18.
Surg Oncol ; 37: 101533, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33601294

RESUMO

OBJECTIVE: To characterize the rates of depression across primary cancer sites, and determine the effects of comorbid depression among surgical cancer patients on established quality of care indicators, non-routine discharge and readmission. METHODS: Patients undergoing surgical resection for cancer were selected from the Nationwide Readmissions Database (2010-2014). Multivariable analysis adjusted for patient and hospital level characteristics to ascertain the effect of depression on post-operative outcomes and 30-day readmission rates. Non-routine discharge encompasses discharge to skilled nursing, inpatient rehabilitation, and intermediate care facilities, as well as discharge home with home health services. RESULTS: Among 851,606 surgically treated cancer patients, 8.1% had a comorbid diagnosis of depression at index admission (n = 69,174). Prevalence of depression was highest among patients with cancer of the brain (10.9%), female genital organs (10.9%), and lung (10.5%), and lowest among those with prostate cancer (4.9%). Depression prevalence among women (10.9%) was almost twice that of men (5.7%). Depression was associated with non-routine discharge after surgery (OR 1.20, CI:1.18-1.23, p < 0.0001*) and hospital readmission within 30 days (OR 1.12, CI:1.09-1.15, p < 0.001*). CONCLUSION: Rates of depression vary amongst surgically treated cancer patients by primary tumor site. Comorbid depression in these patients is associated with increased likelihood of non-routine discharge and readmission.

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.
Genome Biol ; 22(1): 70, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622385

RESUMO

We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. MEDALT appears more accurate than phylogenetics approaches in reconstructing copy number lineage. From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution.The source code of our study is available at https://github.com/KChen-lab/MEDALT .

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