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1.
Oncogene ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005016

RESUMO

Glioblastoma multiforme (GBM) is a highly proliferative and locally invasive cancer with poor prognosis and a high recurrence rate. Although anti-VEGF (vascular endothelial growth factor) therapy offers short-term benefit to GBM patients, this approach fails as the tumor develops into a more invasive and drug-resistant phenotype and ultimately recurs. Recently, both glioma stemlike cells (GSCs) and brain tumor-initiating cells (BTICs) have been implicated in GBM recurrence and its resistance to therapy. We observed that patient-derived GBM cells expressing shRNAs of VEGF or neuropilin-1 (NRP-1) attenuate cancer stem cell markers, inhibit the tumor-initiating cell's neurosphere-forming capacity, and migration. Furthermore, both VEGF and NRP-1 knockdown inhibit the growth of patient-derived GBM xenografts in both zebrafish and mouse models. Interestingly, NRP-1-depleted patient-derived GBM xenografts substantially prolonged survival in mice compared to that of VEGF depletion. Our results also demonstrate that NRP-1 ablation of patient-derived GBM cells improves the sensitivity of TMZ and enhances the overall survival of the respective tumor-bearing mice. This improved outcome may provide insight into the inhibition of GBM progression and effective treatment strategies by targeting NRP-1 in addition to chemotherapy and radiotherapy.

2.
Mol Psychiatry ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005028

RESUMO

Converging evidence increasingly implicates shared etiologic and pathophysiological characteristics among major psychiatric disorders (MPDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Examining the neurobiology of the psychotic-affective spectrum may greatly advance biological determination of psychiatric diagnosis, which is critical for the development of more effective treatments. In this study, ensemble clustering was developed to identify subtypes within a trans-diagnostic sample of MPDs. Whole brain amplitude of low-frequency fluctuations (ALFF) was used to extract the low-dimensional features for clustering in a total of 944 participants: 581 psychiatric patients (193 with SZ, 171 with BD, and 217 with MDD) and 363 healthy controls (HC). We identified two subtypes with differentiating patterns of functional imbalance between frontal and posterior brain regions, as compared to HC: (1) Archetypal MPDs (60% of MPDs) had increased frontal and decreased posterior ALFF, and decreased cortical thickness and white matter integrity in multiple brain regions that were associated with increased polygenic risk scores and enriched risk gene expression in brain tissues; (2) Atypical MPDs (40% of MPDs) had decreased frontal and increased posterior ALFF with no associated alterations in validity measures. Medicated Archetypal MPDs had lower symptom severity than their unmedicated counterparts; whereas medicated and unmedicated Atypical MPDs had no differences in symptom scores. Our findings suggest that frontal versus posterior functional imbalance as measured by ALFF is a novel putative trans-diagnostic biomarker differentiating subtypes of MPDs that could have implications for precision medicine.

3.
Sci Rep ; 10(1): 16357, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004832

RESUMO

Paraneoplastic pemphigus (PNP) is a severe autoimmune syndrome commonly triggered by neoplasms. The prognosis of CLL-associated PNP is dismal due to its refractory course and secondary infection and no standard treatment was recommended. We retrospectively reported six CLL with PNP cases from 842 cases of CLL including diagnosis, treatment and prognosis. The median time between the initial of CLL to PNP was 36 months while the median overall survival from the diagnosis of PNP was 26 months. And three cases died of lung infection while 5 developed pulmonary symptoms. And 5 cases received fludarabine-based chemotherapy before developing PNP, which suggesting fludarabine was one of potential causes of PNP. For the treatment, five patients were rescued by combined regimens including rituximab, methylprednisolone, immunoglobulin, fresh frozen plasma and the last received ibrutinib combined with short-term prednisone. Fludarabine-based regimen may be one of the potential causes of PNP. The combined regimen might shed a new light, while ibrutinib is a promising drug for CLL with PNP, but needs much more evidence. PNP should be carefully treated to guide early diagnosis and intervention for a better prognosis.

4.
Am J Case Rep ; 21: e925151, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021971

RESUMO

BACKGROUND Although the V617F mutation in the Janus kinase 2 (JAK2) gene and the breakpoint cluster region-abl1 (BCR-ABL1) oncogene fusion have been considered mutually exclusive in most myeloproliferative neoplasms (MPNs), many recent studies have described patients with both. This report describes a patient with chronic myelogenous leukemia (CML) and the unusual JAK2 R795S mutation and reviews 23 additional patients with JAK2 gene mutations coexisting with myelofibrosis (MF) and CML. CASE REPORT A 50-year-old woman with MF experienced rapid disease progression 3 weeks later, accompanied by severe abdominal pain and a white blood cell count of 257.45×109/l. Karyotype analysis indicated that she was 46, XY, Philadelphia (Ph) (+) and BCR-ABL1 positive. Bone marrow aspiration after 1 cycle of chemotherapy and treatment with dasatinib showed that her marrow was hypercellular, with an increased number of megakaryocytes and 48.5% myeloblasts expressing the myeloid antigens CD33, CD13, CD34, CD117, and CD71. Next-generation sequencing identified a rare JAK2 R795S mutation. She was diagnosed with CML in blast phase, and was successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). CONCLUSIONS JAK2 gene mutations, including the rare JAK2 R795S mutation, can coexist with BCR-ABL1 in patients with MPNs. The clinical course of MPN in patients with both BCR-ABL1 and JAK2 mutations may be different from that in patients with classical MPNs.

5.
Exp Cell Res ; 396(2): 112331, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33058834

RESUMO

Triple negative breast cancer (TNBC) is a subtype of breast cancer with poorest survival outcome and is prone to metastasis. TUFT1 and the long non-coding RNA (lncRNA), DANCR, play vital roles in metastasis and progression of various cancers. However, the correlation between TUFT1 and DANCR in TNBC and their downstream molecular mechanisms are still undetermined. We demonstrated that upregulation of TUFT1 in TNBC was related to a worse survival in TNBC patients. The TNBC cells invasiveness was augmented by TUFT1 in a dose-dependent manner, while inhibiting TUFT1 repressed the invasiveness. Particularly, the expression of TUFT1 was positively correlated with the expression of DANCR in TNBC tissues. In addition, TUFT1 increased DANCR expression, while silencing DANCR ameliorated the invasiveness of TNBC cells induced by TUFT1. As demonstrated, TUFT1 interacted with miR-874-3p. Subsequently, qRT-PCR together with luciferase reporter further demonstrated that DANCR acted as competing endogenous (ceRNA) for miR-874-3p, thereby regulating the de-repression of SOX2 and advancing epithelial-mesenchymal transition (EMT) in TNBC. The present research shows that TUFT1 promotes the malignant development in TNBC via enhancing the expression of DANCR. The upregulation of DANCR may contribute to the progression and tumor invasiveness of TNBC, considering that DANCR functions as a miR-874-3p sponge, thus modulating SOX2 positively. Collectively, the present study explored the molecular mechanism underlying TUFT1 in TNBC, raising a TUFT1-mediated therapy for the treatment of patients with TNBC.

6.
BMC Psychiatry ; 20(1): 496, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028273

RESUMO

BACKGROUND: Delirium is a common complication in elderly patients with total hip arthroplasty (THA) for hip fracture. The mechanism of postoperative delirium (POD) is associated with the neuroinflammatory process. The aim of this study was to the incidence and perioperative risk factors of POD and investigate whether NLR could serve as a potential marker for POD in elderly patients with THA for hip fracture. METHODS: This was a multicenter prospective study, we included elderly patients with THA for hip fracture under general anesthesia. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut point of NLR for POD. The relationship between NLR and POD was analyzed by multivariable analysis. RESULTS: Seven hundred eighty patients (mean age 73.33 ± 7.66) were eligible for inclusion in the study. 23.33% (182/780) of patients had POD. ROC curve analysis showed that the optimal cut point of NLR for POD was NLR ≥ 3.5. Compared with no POD, higher NLR, older age, diabetes, and higher neutrophil count were more likely in patients with POD(P < 0.05). Multivariate logistic regression analysis showed that NLR ≥ 3.50 [adjusted odds ratio(aOR), 3.93; confidence interval (CI), 2.47-6.25; P < 0.001)], older age (aOR, 1.04; 95%CI, 1.02-1.07; P = 0.001), diabetes (aOR, 1.58; 95% CI, 1.06-2.36; P = 0.025),higher neutrophil count (aOR, 1.25; 95%CI, 1.15-1.35; P < 0.001) were associated with increased risk of POD. CONCLUSIONS: Older age, diabetes, higher neutrophil count, and NLR ≥ 3.5 were independent risk factors for POD, and NLR can be used as a potential marker for prediction of delirium in elderly patients with THA for hip fracture.

7.
Trials ; 21(1): 850, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054842

RESUMO

BACKGROUND: Extended exposure to high concentrations of PM2.5 changes the human microbiota profile, which in turn may increase morbidity and mortality due to respiratory system damage. A balanced microecosystem is crucial to human health, and certain health-related problems may be addressed by effective microecosystem regulation. Recent studies have confirmed that probiotics may reduce the incidence of respiratory diseases. However, few studies have investigated probiotic treatment outcomes in subjects exposed to high concentrations of PM2.5. METHODS: This study is designed as a prospective, randomized, participants- and assessor-blinded, placebo-controlled trial. One hundred and twenty eligible volunteers recruited from October 2019 to July 2020 in downtown Chengdu, China, will be treated with either probiotics or placebo over 4 consecutive weeks. The primary outcome will be 16SrRNA sequencing assay data from nasal and intestinal secretions. Secondary outcomes will be pulmonary function, score on a gastrointestinal symptom rating scale, COOP/WONCA charts, and the Short-Form Health Survey 36 for quality of life. Results will be analyzed to assess differences in clinical efficacy between groups. Six-month follow-up examinations will evaluate the long-term value of probiotics on cardiovascular and respiratory disease end-point events. DISCUSSION: We will explore the characteristics of nasal and intestinal microbiota in a population with high exposure to PM2.5. Probiotics and placebo interventions will be tested for efficacy in microbial balance regulation, effects on lung and physical functions, and quality of life improvement. This study is expected to provide reliable evidence to support the widespread promotion of probiotics in clinical practice for the protection of individuals with high exposure to PM2.5. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900025469 . Registered on 27 August 2019.

9.
J Am Med Inform Assoc ; 27(10): 1612-1624, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33059367

RESUMO

OBJECTIVE: The Unified Medical Language System (UMLS) is 1 of the most successful, collaborative efforts of terminology resource development in biomedicine. The present study aims to 1) survey historical footprints, emerging technologies, and the existing challenges in the use of UMLS resources and tools, and 2) present potential future directions. MATERIALS AND METHODS: We collected 10 469 bibliographic records published between 1986 and 2019, using a Web of Science database. graph analysis, data visualization, and text mining to analyze domain-level citations, subject categories, keyword co-occurrence and bursts, document co-citation networks, and landmark papers. RESULTS: The findings show that the development of UMLS resources and tools have been led by interdisciplinary collaboration among medicine, biology, and computer science. Efforts encompassing multiple disciplines, such as medical informatics, biochemical sciences, and genetics, were the driving forces behind the domain's growth. The following topics were found to be the dominant research themes from the early phases to mid-phases: 1) development and extension of ontologies and 2) enhancing the integrity and accessibility of these resources. Knowledge discovery using machine learning and natural language processing and applications in broader contexts such as drug safety surveillance have recently been receiving increasing attention. DISCUSSION: Our analysis confirms that while reaching its scientific maturity, UMLS research aims to boundary-span to more variety in the biomedical context. We also made some recommendations for editorship and authorship in the domain. CONCLUSION: The present study provides a systematic approach to map the intellectual growth of science, as well as a self-explanatory bibliometric profile of the published UMLS literature. It also suggests potential future directions. Using the findings of this study, the scientific community can better align the studies within the emerging agenda and current challenges.

10.
Global Spine J ; : 2192568220965566, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063550

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to assess long-term radiographic and clinical outcomes in Lenke 5C adolescent idiopathic scoliosis (AIS) patients after posterior selective fusion. METHODS: Lenke 5C AIS patients who underwent posterior selective thoracolumbar/lumbar (TL/L) fusion in our hospital from January 2007 to January 2010 were recruited. Radiographic parameters were measured preoperatively and at the 3-month, 1-year, 2-year, 5-year, and 10-year follow-ups. The SRS-22 (Scoliosis Research Society) questionnaire was used to assess the clinical outcomes. RESULTS: We included 37 patients who underwent posterior selective TL/L fusion surgery in our study, and the mean follow-up time was 11.26 ± 0.85 years. The average preoperative Cobb angles of the thoracic and TL/L curves were 24.0 ± 9.0° and 45.4 ± 6.3°, respectively, which were corrected to 12.2° and 12.4° at the 3-month follow-up postoperatively, with correction losses of 2.2° and 1.5° at the 10-year follow-up. In the sagittal plane, the degree of thoracic kyphosis (TK) gradually increased over the follow-up period. The proximal junctional angle (PJA) also gradually increased from 6.7 ± 4.6 to 13.7 ± 5.6 during the follow-up period. For the clinical outcomes, correction surgery improved the SRS-22 scores in each domain, especially in the self-image domain. CONCLUSIONS: Posterior selective TL/L fusion can effectively correct spinal deformities, leading to stable outcomes for 10 years postoperatively. During the follow-up period, the degree of TK presented an increasing trend that remained almost constant after the 1-year follow-up. Moreover, the variation in the PJA was highly significant in the postoperative period, and it showed an increasing trend until the 2-year follow-up.

11.
New Phytol ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33034042

RESUMO

The SKU5 similar (SKS) genes encode a family of multi-copper-oxidase-like proteins with cupredoxin domains similar to those in laccase and ascorbate oxidase. Although SKS proteins are known function in root growth and cotyledon vascular patterning in Arabidopsis, their role in plant reproductive processes is poorly understood. Here, we identified a seed mutant of maize (Zea mays), generated by ethyl methane sulfonate (EMS) mutagenesis, that we designated defective kernel-zk1 (dek-zk1). The mutant produced small, shriveled kernels with an aberrant basal endosperm transfer layer (BETL) and placento-chalazal (PC) layer and irregular starch granules. Map-based cloning revealed that Dek-zk1 encodes a SKU5 similar 13 (GenBank: ONM36900.1), so it was named ZmSKS13. ZmSKS13 comprises a paralogous pair with Zm00001d012524, but the transcript abundance of ZmSKS13 in developing kernels is 15-fold higher than that of Zm00001d012524, resulting in dek-zk1 mutation conveying a distinct kernel phenotype. ZmSKS13 loss of function led to overaccumulation of reactive oxygen species (ROS) and severe DNA damage in the nucellus and BETL and PC layer cells, and exogenous antioxidants significantly alleviated the defects of the mutant kernels. Our results thus demonstrate that ZmSKS13 is a novel regulator that plays a crucial role in kernel development in maize through modulating ROS homeostasis.

12.
Molecules ; 25(20)2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33050462

RESUMO

Polyphenols are micronutrients that are widely present in human daily diets. Numerous studies have demonstrated their potential as antioxidants and anti-inflammatory agents, and for cancer prevention, heart protection and the treatment of neurodegenerative diseases. However, due to their vulnerability to environmental conditions and low bioavailability, their application in the food and medical fields is greatly limited. Nanoformulations, as excellent drug delivery systems, can overcome these limitations and maximize the pharmacological effects of polyphenols. In this review, we summarize the biological activities of polyphenols, together with systems for their delivery, including phospholipid complexes, lipid-based nanoparticles, protein-based nanoparticles, niosomes, polymers, micelles, emulsions and metal nanoparticles. The application of polyphenol nanoparticles in food and medicine is also discussed. Although loading into nanoparticles solves the main limitation to application of polyphenolic compounds, there are some concerns about their toxicological safety after entry into the human body. It is therefore necessary to conduct toxicity studies and residue analysis on the carrier.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33052852

RESUMO

Salient object detection has undergone a very rapid development with the blooming of Deep Neural Network (DNN), which is usually taken as an important preprocessing procedure in various computer vision tasks. However, the down-sampling operations, such as pooling and striding, always make the final predictions blurred at edges, which has seriously degenerated the performance of salient object detection. In this paper, we propose a simple yet effective approach, i.e., Hierarchical and Interactive Refinement Network (HIRN), to preserve the edge structures in detecting salient objects. In particular, a novel multi-stage and dual-path network structure is designed to estimate the salient edges and regions from the low-level and high-level feature maps, respectively. As a result, the predicted regions will become more accurate by enhancing the weak responses at edges, while the predicted edges will become more semantic by suppressing the false positives in background. Once the salient maps of edges and regions are obtained at the output layers, a novel edge-guided inference algorithm is introduced to further filter the resulting regions along the predicted edges. Extensive experiments on several benchmark datasets have been conducted, in which the results show that our method significantly outperforms a variety of state-of-the-art approaches.

14.
Nature ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057201

RESUMO

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown1. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer2-4 and coronary heart disease5-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)6. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.

15.
Br J Pharmacol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068011

RESUMO

BACKGROUND AND PURPOSE: Acute kidney injury (AKI) is a common and critical illness, resulting in severe morbidity and a high mortality. There is a considerable interest in identifying novel molecular targets for management of AKI. Here, we investigated the potential role of the circadian clock components Rev-erbα/ß in regulation of ferroptosis and AKI. EXPERIMENTAL APPROACH: AKI model was established by treating mice with folic acid (FA). Regulatory effects of Rev-erbα/ß on AKI and ferroptosis were determined using single gene knockout (Rev-erbα-/- and Rev-erbß-/- ) mice, incomplete double knockout (icDKO, Rev-erbα+/- Rev-erbß-/- ) mice, and cells with erastin-induced ferroptosis. Targeted antagonism of Rev-erbα/ß to alleviate AKI and ferroptosis was assessed using the small-molecule antagonist SR8278. Transcriptional gene regulation was investigated using luciferase reporter, mobility shift, and chromatin immunoprecipitation assays. KEY RESULTS: Loss of Rev-erbα or Rev-erbß reduced the sensitivity of mice to FA-induced AKI and eliminated the circadian time-dependency in disease severity. This coincided with less extensive ferroptosis, a main cause of FA-induced AKI. Moreover, icDKO mice were more resistant to FA-induced AKI and ferroptosis as compared to single gene knockout mice. Supporting this, targeting Rev-erbα/ß by SR8278 attenuated ferroptosis to ameliorate FA-induced AKI in mice. Mechanistically, Rev-erbα/ß promoted ferroptosis by repressing the transcription of Slc7a11 and HO-1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. CONCLUSION AND IMPLICATIONS: Targeted inhibition of Rev-erbα/ß limits ferroptosis to ameliorate FA-induced AKI in mice. The findings may have implications for improved understanding of circadian clock-controlled ferroptosis and for formulating new strategies to treat AKI.

16.
Nat Commun ; 11(1): 5035, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028823

RESUMO

Aliphatic α,ω-dicarboxylic acids (DCAs) are a class of useful chemicals that are currently produced by energy-intensive, multistage chemical oxidations that are hazardous to the environment. Therefore, the development of environmentally friendly, safe, neutral routes to DCAs is important. We report an in vivo artificially designed biocatalytic cascade process for biotransformation of cycloalkanes to DCAs. To reduce protein expression burden and redox constraints caused by multi-enzyme expression in a single microbe, the biocatalytic pathway is divided into three basic Escherichia coli cell modules. The modules possess either redox-neutral or redox-regeneration systems and are combined to form E. coli consortia for use in biotransformations. The designed consortia of E. coli containing the modules efficiently convert cycloalkanes or cycloalkanols to DCAs without addition of exogenous coenzymes. Thus, this developed biocatalytic process provides a promising alternative to the current industrial process for manufacturing DCAs.

17.
Stem Cell Res ; 49: 102014, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33039806

RESUMO

Thalassemia is a group of single-gene recessive inherited hemoglobin disorders caused by a mutation or deletion of one or more globin genes, which results in abnormal globin chain synthesis and hemoglobin formation. In this study, human iPSC lines HNMUi002-A, HNMUi003-A, HNMUi004-A, HNMUi005-A, HNMUi006-A, HNMUi007-A, HNMUi008-A, HNMUi009-A, HNMUi010-A were generated from the amniotic fluid cells or urine-derived cells isolated from 9 patients with thalassemia. The iPSC lines exhibited the normal karyotype, expressed pluripotency markers, and carried α- or ß- globin gene mutations. These pluripotent stem cell lines will serve as useful tools for studying pathophysiological mechanism of thalassemia.

18.
Sci Total Environ ; 755(Pt 2): 142419, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33049525

RESUMO

Vegetation is a crucial component of terrestrial ecosystems, and its changes are driven mainly by a combination of climate change and human activities. This paper aims to reveal the relationship between vegetation and climate change by using the normalized difference vegetation index (NDVI) and standardized precipitation evapotranspiration index (SPEI), and to find the cause of vegetation change by performing residual analysis on the Loess Plateau during the period from 2000 to 2016. The results showed that the NDVI on the Loess Plateau exhibited an increase of 0.086 per decade, and an increasing trend was observed across 94.86% of the total area. The relationship between the NDVI and SPEI was mainly positive, and the correlation increased as the time scale of the SPEI lengthened, indicating that long-term water availability was the major climate factor affecting vegetation growth. Residual analysis indicated that climate change was responsible for 45.78% of NDVI variation, while human activities were responsible for 54.22%. In areas with degraded vegetation, the relative roles of climate change and human activities were 28.11% and 72.89%, respectively. In addition, the relative role of climate change increased with an increase in the time scales, implying that the long-term NDVI trend was more sensitive to climate change then the short-term trend. The results of this study are expected to enhance our understanding of vegetation changes under climate change and human activities and provide a scientific basis for future ecological restoration in arid regions.

19.
Phytochemistry ; 180: 112534, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065407

RESUMO

Fourteen undescribed diterpenoids caryopterisoids D - Q, three undescribed iridoid glucoside derivatives caryopterisides F - H, and 8 known diterpenoids were isolated from the 95% aqueous ethanolic extract of Caryopteris glutinosa. Their structures were elucidated on the basis of spectroscopic data analysis and chemical derivation studies. The structure and absolute configuration of caryopterisoid D were confirmed by X-ray crystallographic analysis. Caryopterisoids K and R, royleanone, 6α-hydroxydemethylcryptojaponol, and teuvincenone E were shown to reduce the biosynthesis of estrogen E2 with IC50 values from 0.25 to 3.06 µM in cell-based estrogen biosynthesis assays system.

20.
Chemosphere ; 264(Pt 2): 128505, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33068969

RESUMO

We sought to evaluate whether essential and toxic metals are cross-sectionally related to blood lipid levels using data among adults from Shimen (n = 564) and Huayuan (n = 637), two counties with different exposure profiles in Hunan province of China. Traditional and grouped weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were performed to assess association between exposure to a mixture of 22 metals measured in urine or plasma, and lipid markers. Most of the exposure levels of metals were significantly higher in Shimen area than those in Huayuan area (all P-values < 0.001). Traditional WQS regression analyses revealed that the WQS index were both significantly associated with lipid markers in two areas, except for the HDL-C. Grouped WQS revealed that essential metals group showed significantly positive associations with lipid markers except for HDL-C in Huayuan area, while toxic metals group showed significantly negative associations except for HDL-C and LDL-C in Huayuan area. There were no significant joint effects, but potential non-linear relationships between metals mixture and TC or LDL-C levels were observed in BKMR analyses. Although consistent significantly associations of zinc and titanium with TG levels were found in both areas, the metals closely related to other lipid markers were varied by sites. Additionally, the BKMR analyses revealed an inverse U shaped association of iron with LDL-C levels and interaction effects of zinc and cadmium on LDL-C in Huayuan area. The relationship between metal exposure and blood lipid were not identical against different exposure profiles.

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