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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 311-315, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812392

RESUMO

OBJECTIVE: To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement. METHODS: A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification. RESULTS: Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×109/L. These patients presented different immunophenotype, including 3 cases of common B-ALL and 2 cases of pre B-ALL. Four patients carried a normal karyotype and 1 patient carried 46, XY, der (20) [22]/46, XY[2]. For the children with P2RY8-CRLF2 gene rearrangement, 1 patient (20%) could not achieve complete remission (CR), and minimal residual disease (MRD) of 2 patients (40%) was higher than 1% on day 33 of induction chemotherapy; while in group without P2RY8-CRLF2 gene rearrangement, all the patient achieved CR, and MRD in 6 patients (5.8%) was higher than 1% on day 33 of induction chemotherapy. The 3 year event-free survival (EFS) of ALL children in group with P2RY8-CRLF2 gene rearrangement was significantly lower than that in group without P2RY8-CRLF2 gene rearrangement (60.0%±21.9% vs 85.9%±3.9%) (P<0.05). CONCLUSION: The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Rearranjo Gênico , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Receptores de Citocinas/genética , Receptores Purinérgicos P2Y/genética
2.
Nutrients ; 13(3)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802324

RESUMO

BACKGROUND: Compliance with dietary guidelines among pregnant women can positively influence not only their own health but also the health of their babies. Measuring the compliance requires professional skills in nutrition and dietary counseling. In China, few simple and effective techniques assess dietary quality among pregnant women, especially in rural areas. We aimed to establish a new simple and effective assessment technique, the "Chinese Dietary Guidelines Compliance Index for Pregnant Women (CDGCI-PW)" and assess the association between maternal dietary compliance and risks of pregnancy complications. METHODS: The CDGCI-PW consists of 13 main components which were based on the 2016 edition of the Chinese dietary guidelines for pregnant women. Each component was assigned a different score range, and the overall score ranged from 0 to 100 points. The Tongji Maternal and Child Health Cohort study (from September 2013 to May 2016) was a prospective cohort study designed to examine maternal dietary and lifestyle effects on the health of pregnant women and their offspring. The maternal diet during the second trimester was compared with the corresponding recommended intake of the Chinese balanced dietary pagoda for pregnant women to verify their compliance with dietary guidelines. The association between maternal dietary quality and risks of pregnancy complications was estimated by regression analysis. Receiver operating characteristic (ROC) curves were constructed to identify the optimal cut-off values of CDGCI-PW for gestational hypertension and gestational diabetes mellitus (GDM). RESULTS: Among the 2708 pregnant women, 1489 were eventually followed up. The mean CDGCI-PW score was 74.1 (standard deviation (SD) 7.5) in the second trimester. The majority of foods showed the following trend: the higher the CDGCI-PW score, the higher the proportion of pregnant women who reported food intake within the recommended range. Moreover, a higher maternal CDGCI-PW score was significantly associated with lower risks of gestational hypertension [odds ratio (OR) (95% confidence interval [(CI): 0.30 (0.20, 0.37)] and GDM [OR (95% CI): 0.38 (0.31, 0.48)]. The optimal CDGCI-PW cut-off value for gestational hypertension was ≥68.5 (sensitivity 82%; specificity: 61%; area under the ROC curve, AUC = 0.743), and the optimal CDGCI-PW cut-off score for GDM was ≥75.5 (sensitivity 43%; specificity: 81%; area under the ROC curve, AUC = 0.714). CONCLUSIONS: The CDGCI-PW is a simple and useful technique that assesses maternal diet quality during pregnancy, while adherence to the CDGCI-PW is associated with a lower risk of gestational hypertension and GDM.

3.
Plant Dis ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33719544

RESUMO

Michelia alba (common name: white champaca), native to Indonesia, is a preciously ornamental and medicinal plant in the west and southeast of China and widely distributed in Nanning, Guangxi, China (Hou et al. 2018). In May 2020, a foliar disease of M. alba was observed in Nanning (22°51' N; 108°17' E), Guangxi, China, present on ca. 20-30% of the leaves. The disease began to develop from the margins of leaves in most cases. The symptoms recorded were light yellow spots, which gradually developed into ellipsoidal to irregular brown spots, surrounded by a wide yellow halo. The spots gradually enlarged in size and became grey-brown, with the dimension of 3.5 × 2.8 to 11.0 × 3.5 cm, even more than half of leaf area. In the later stage of infection, these spots coalesced resulting in necrosis and early shedding of the leaves. Sometimes black acervuli were observed on some lesions. For isolation of the fungus, ten symptomatic leaves were randomly sampled from five trees and washed with sterile water. Small pieces of infected tissue (about 4 mm2) were surface disinfected in 75% alcohol for 30 s and in 0.1% aqueous solution of mercury chloride for 1 min. Finally these tissue pieces were rinsed three times with sterile water, plated on potato dextrose agar (PDA) and then incubated for 7 days at 28℃ with a photoperiod of 12 h. Fifteen strains with similar morphological characterizations were isolated, and five representative isolates (BL-1 to BL-5) were purified. These cultures gave rise to grey-white colonies with bright orange conidial masses with contained one-celled, hyaline, guttulate conidia, measuring 12.68-20.70 × 4.27-7.84 µm (average 15.36 × 5.35 µm, n=100). Appressoria formed from conidia were brown, ellipsoidal or inverted trapezoid and measured 6.36-12.13 × 5.07-7.39 µm (average 8.29 × 6.36 µm, n=30). These morphological characteristics were similar to those of the Colletotrichum gloeosporioides species complex (Weir et al. 2012). To confirm identification, genomic DNA from mycelium of these five isolates was extracted, and the sequence of internal transcribed spacer (ITS), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), calmodulin (CAL) and ß-tubulin (TUB2) were amplified (Zhang et al. 2020), and the GenBank accession numbers for the sequences were MW186173 to MW186177 (ITS), MW161290 to 161294 (CHS-1), MW161295 to MW161299 (GAPDH), MW161285 to 161289 (ACT), MW084710 to 084714 (CAL) and MW161300 to MW161304 (TUB2). The phylogenetic tree of six combined genes of the five isolates clustered with Colletotrichum siamense strains (CBS 125378, ICMP 17795 and ICMP 18121). Therefore, the isolates were identified as C. siamense. Five isolates (BL-1 to BL-5) were tested for pathogenicity. Wounded and unwounded detached healthy leaves were inoculated using mycelial discs (5 mm in diameter) and conidial suspensions (with the concentration of 1 × 105 conidia/ml) at the same time, incubated in a growth chamber at 25-30℃ (85-90% relative humidity, with a photoperiod of 12 h). Three leaves (wounded left half blade and unwounded right half blade) were inoculated with different methods for each isolate, and the tests were repeated three times. Four days after inoculation, leaf spots were observed on all wounded leaves, while 5-10% of the unwounded leaves showed lesions. Control leaves inoculated with PDA discs and sterile water remained symptomless. Colletotrichum. siamense was re-isolated from the lesions, confirming Koch's postulates. At least 60 plant species have been reported to be infected by C. siamense worldwide (Ji et al. 2019). To our knowledge, this is the first report of C. siamense causing leaf spot on M. alba in China.

4.
Nutrition ; 87-88: 111193, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33774421

RESUMO

OBJECTIVE: Information is limited regarding the possible relationship between diet-related inflammation and the risk of gestational diabetes mellitus (GDM). This study investigated the association between the inflammatory potential of the diet, measured by the dietary inflammatory index (DII), and GDM risk in pregnant Chinese women. METHODS: This study included 2639 eligible women from the Tongji Maternal and Child Health Cohort. Dietary intake was assessed by a validated semiquantitative food frequency questionnaire and was used to calculate the DII score. The DII was then validated using C-reactive protein measurements in a subsample of 133 pregnant women. GDM diagnoses were collected from medical records based on the results of a 75 g oral glucose tolerance test at 24 to 28 wk gestation. Multivariable-adjusted logistic regression models were performed to estimate the odds ratios (ORs) for GDM risk by DII score, modeled continuously and in tertiles. RESULTS: Of the 2639 participants, 13.1% were diagnosed with GDM. DII scores ranged from -4.45 to 3.15 and were positively associated with C-reactive protein (adjusted ß : 1.28, 95% confidence interval [CI]: 0.16, 2.40; P trend = 0.023) when comparing DII tertile 3 (most pro-inflammatory) to tertile 1 (most anti-inflammatory). A significant and positive association was observed between DII scores and GDM risk (adjusted OR: 1.43; 95% CI: 1.05, 1.95; P trend = 0.022) comparing the highest versus lowest tertiles. The stratified analysis showed that this association was stronger in pregnant women who were overweight or obese before pregnancy (adjusted OR: 2.20; 95% CI: 1.03, 4.69). CONCLUSIONS: These findings suggest that a higher DII score, corresponding to a more proinflammatory diet, is associated with a higher risk of GDM, particularly in pregnant women who were overweight or obese before pregnancy.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 49-55, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554796

RESUMO

OBJECTIVE: To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL). METHODS: The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy. RESULTS: One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033). CONCLUSION: The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Intervalo Livre de Doença , Humanos , Fenótipo , Prognóstico , Indução de Remissão , Estudos Retrospectivos
6.
PLoS One ; 16(2): e0245530, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596212

RESUMO

Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs' diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.

7.
J Exp Clin Cancer Res ; 40(1): 67, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588913

RESUMO

BACKGROUND: Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear. METHODS: Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5'tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5'tiRNA-His-GTG. The regulation of 5'tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments. RESULTS: Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5'tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5'tiRNA-His-GTG in CRC and found that targeting 5'tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5'tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5'tiRNA-His-GTG, which renders 5'tiRNA-His-GTG to "turn off" hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes. CONCLUSIONS: In summary, the findings revealed a specific 5'tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.

8.
Chem Commun (Camb) ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33459300

RESUMO

Carbon-centred chirality of the pincer-type cyclometalated ligands is transferred to the helical chirality of dinuclear and tetranuclear Pd(ii) arylacetylide complexes, and hence phosphorescence with quantum yields up to 50% and dissymmetry factors in the 10-3 scale from the metal-metal-to-ligand charge-transfer excited states has been recorded in diluted solutions.

9.
Drug Deliv ; 28(1): 183-194, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33427520

RESUMO

Endostatin (ES) can effectively inhibit neovascularization in most solid tumors and has the potential to make oxygen delivery more efficient and increase the efficacy of radiotherapy (RT). With a short half-life, ES is mainly administered systemically, which leads to low intake in tumor tissue and often toxic systemic side effects. In this study, we used hyaluronic acid-tyramine as a carrier to synthesize an ES-loaded hydrogel drug (ES/HA-Tyr) that can be injected locally. ES/HA-Tyr has a longer half-life and fewer systemic toxic side effects, and it exerts a better anti-angiogenic effect and anti-tumor effect with RT. In vitro, ES/HA-Tyr showed sustained release in the release assay and a stronger ability to inhibit the proliferation of human umbilical vascular endothelial cells (HUVECs) in the MTT assay; it exhibited a more potent effect against HUVEC invasion and a stronger anti-angiogenic effect on HUVECs in tube formation. In vivo, ES/HA-Tyr increased local drug concentration, decreased blood drug concentration, and caused less systemic toxicity. Further, ES/HA-Tyr effectively reduced tumor microvessel density, increased tumor pericyte coverage, decreased tumor hypoxia, and increased RT response. ES/HA-Tyr + RT also had increased anti-tumor and anti-angiogenic effects in Lewis lung cancer (LLC) xenograft models. In conclusion, ES/HA-Tyr showed sustained release, lower systemic toxicity, and better anti-tumor effects than ES. In addition, ES/HA-Tyr + RT enhanced anti-angiogenic effects, reduced tumor hypoxia, and increased the efficacy of RT in LLC-bearing mice.

10.
Matern Child Nutr ; 17(1): e13043, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32815668

RESUMO

We aimed to assess protein nutrition status during pregnancy by maternal plasma total protein (MTP) levels in urban pregnant women and to explore the association between the trimester-specific MTP levels and risk of preterm birth (PTB). A prospective design was conducted in 3,382 mother-newborn pairs with the second-trimester maternal MTP information and in 3,478 mother-newborn pairs with the third-trimester MTP information. Multiple Cox proportional hazard regression and multiple linear regression were used to analyse the associations between MTP levels and PTB risk as well as gestational duration, respectively. Nearly all the second-trimester MTP levels were within the clinical reference range, but more than 40% of the third-trimester MTP levels were less than the lower limit of normal. No significant association was found between the second-trimester MTP level and PTB risk. However, the adjusted hazard ratios (HRs) of PTB across increasing quartiles of the third-trimester MTP levels were 1.00 (reference), 0.59 (0.36, 0.95), 0.35 (0.20, 0.60), and 0.32 (0.19, 0.53) (p for trend < 0.001), respectively. Each standard deviations increment of the third-trimester MTP was associated with increase of 0.13 weeks in gestational duration. Moreover, stratified analyses showed that the effects of third-trimester MTP on PTB risk and gestational duration were stronger in pregnant women carrying female offspring than those carrying male offspring (p for interaction < 0.05). The third-trimester MTP level was inversely associated with PTB risk and was positively associated with gestational duration. Improving third-trimester MTP level may be helpful for preventing PTB.

11.
Drug Deliv ; 27(1): 1524-1534, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33118422

RESUMO

This study was conducted to determine the antitumor effects and ability of an anlotinib (AL) hydrogel (AL-HA-Tyr) to reduce toxicity in a mouse model of Lewis lung cancer (LLC). We constructed a drug carrier system for AL, verified its effectiveness and systemic safety, and provided a preliminary experimental foundation for clinical carrier transformation. AL-HA-Tyr was prepared by encapsulating AL with hyaluronic acid-tyramine (HA-Tyr) conjugates. Colony and tube formation assays showed that AL-HA-Tyr restrained the proliferation of human umbilical vein endothelial cells (HUVECs) and LLC cells, respectively, in vitro, and that AL exerted significant anti-angiogenesis and anti-tumor effects. The invasion and migration of HUVECs and LLC cells were efficiently suppressed by AL according to transwell assays. HUVEC and LLC cell-cycle and apoptosis analysis clarified the direct anti-tumor effects of AL-HA-Tyr. Mice engrafted with LLC cells in vivo were administered oral saline, oral AL, or an intratumoral injection of HA-Tyr or AL-HA-Tyr. The results showed that AL-HA-Tyr obviously reduced visceral toxicity and decreased Ki67 and VEGF-A expression in tumor cells compared with AL. Furthermore, AL-HA-Tyr significantly prolonged the survival of tumor-bearing mice. Overall, AL-HA-Tyr enhanced antitumor effects and reduced toxicity in the LLC model. It provided a foundation for the clinical transformation of drug carrier systems.

12.
Toxicology ; 445: 152599, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32976958

RESUMO

Ginkgolide B (GB), a main constituent of Ginkgo biloba extracts, reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease (NAFLD) in obese mice, but the potential mechanism is unclear. Here we investigated the attenuated effects of GB on the disorder of lipid metabolism, oxidative stress and iron deposition in NAFLD and its potential mechanism associated with ferroptosis. Our preliminary research focused on high fat diet (HFD)-induced ApoE-/-mice gavaged with GB (20 and 30 mg kg-1•d-1, approximately equal to the human dose of 2 and 3 mg kg-1•d-1, respectively) and palmitic acid and oleic acid (PA/OA)-induced HepG2 cells treated with GB (4, 8, 16 µg/mL), respectively. Hepatic injury was assessed via biochemical, histopathological and immunohistochemical evaluations. In order to examine the mechanism of GB on ferroptosis-regulated pathway, we analyzed the expression levels of ferroptosis-related proteins, including nuclear factor erythroid 2 (Nrf2), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), transferrin receptor-1 (TFR1) and ferritin heavy chain-1 (FTH1) in vivo and vitro experiments by Western blotting. In order to further verify the correlation pathway of ferroptosis, after Nrf2 short hairpin RNA interference, we analyzed the effects of GB on Nrf2 pathway. Both HFD-fed mice and PA/OA-induced HepG2 cells displayed ferroptosis-based panel of biomarkers such as iron overload with the up-regulation of TFR1 and the down-regulation of FTH1, lipid peroxidation and inhibition of Nrf2 activity, which further induced GPX4 and HO-1 levels. Remarkably, after Nrf2 interference, GB treatment significantly increased Nrf2 expression, indicating that GB exerted anti-ferroptosis effects by activation of Nrf2 pathway. Our results are preliminarily illustrated that GB treatment has a specific effect on lipid accumulation and oxidative stress caused ferroptosis in NAFLD, possibly through Nrf2 signaling pathway.

13.
Plant Dis ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910727

RESUMO

Crassocephalum crepidioides (Benth.) S. Moore, native to tropical Africa, is an important invasive weed in many countries, seriously threatening the safety of agricultural ecosystem. During December 2018, 100% of C. crepidioides plants exhibited leaf spots in the Kudzu (Pueraria lobata) garden in Tianlin County, Baise City, Guangxi, China (24°40'20.42″N, 106°11'33.51″E), but Kudzu was not affected by this disease. The leaf spots appeared as small brown spots surrounded by a yellow-green halo initially, enlarged to subrotund or irregular in shape, slightly sunken, then developed as a dark brown to dark spot with grey-white necrotic center (Supplementary Fig. 1 a,b), and exuded an orange droplet under high humidity conditions (Supplementary Fig. 1 c). Symptomatic leaf tissues were cut into small pieces (5 x 5 mm) from the junction of necrotic and healthy tissues, and small pieces were disinfected in 75% ethanol solution for 30 s and 0.1% mercury dichloride for 30 sec, then rinsed with sterile water 3 times. These tissues were plated onto potato dextrose agar (PDA) medium and incubated in a thermostatic incubator at 28°C under natural sunlight conditions. Four isolates with similar morphological features were obtained after purification. Colonies of these isolates exhibited creme-orange margins and aerial mycelium was sparse. The colonies formed concentric circles on the surface that were fusco-black, violet-slate and vinaceus-grey (from centre to edge), fusco-black on the reverse after 7 days (Supplementary Fig. 2 a,b), and then the pycnidia and conidia produced for about 30 days (Supplementary Fig. 2 c). Pycnidia of representative isolate YTH-12 were black, subglobose, and unilocular, 95.60-168.27 µm (average 128.32 µm) (n = 40) in diameter. The ostiole was single and central, slightly papillate to papillate and occasionally rostrate (Supplementary Fig. 2 d). Conidia were hyaline, oval to elliptical, aseptate, 2.30 to 5.83 × 1.42 to 3.50 µm (average, 4.36 × 2.03 µm) (n = 50) (Supplementary Fig. 2 e). These morphological characters are consistent with those described for Stagonosporopsis vannaccii (Crous et al. 2019). To further identify the isolate YTH-12, the rDNA internal transcribed spacer (ITS) region, 28s large subunit ribosomal RNA (LSU), RNA polymerase II second largest subunit (RPB2) gene and ß-tubulin (TUB2) gene were amplified by polymerase chain reaction using the primer pairs ITS1/ITS4 (White et al. 1990), LR0R (Rehner and Samuels 1994)/LR7 (Vilgalys and Hester 1990), Btub2Fd/Btub4Rd (Woudenberg et al. 2009) and RPB2-5F2 (Sung et al. 2007)/fRPB2-7cR (Liu et al. 1999), respectively. The PCR products were purified and sequenced by Sangon Biotech Co. Ltd. (Shanghai, China). The sequences were deposited in GenBank (accession nos. MN892355, MN893911, MN905510 and MN905511). The ITS (522 bp), LSU (1313 bp), TUB2 (380 bp) and RPB2 (1193 bp) nucleotide sequences showed 100% identity to S. vannaccii strain LFNO148 (accession nos. MK519453, MK519452, MK519454 and MN534891). Phylogenetic analysis based on the multi-locus sequences of ITS, LSU, RPB2 and TUB2 was performed in MEGA version 6.0 (Chen et al. 2015). The relative stability of the branches was evaluated by bootstrapping with 1000 replications. The isolate YTH-12 was placed in the same clade as S. vannaccii with 100% bootstrap support. Based on morphology and molecular analyses, this pathogen was identified as S. vannaccii. To satisfy Koch's postulates, the isolate YTH-12 was inoculated on leaves of C. crepidioides plants. Twenty punctured leaves and twenty unwounded leaves were inoculated with a 5-mm-diameter mycelial disc, respectively. Leaves inoculated with sterile PDA discs were used as blank controls. Plants were maintained in a growth chamber (25°C-28°C and relative humidity 80%-90%). Brown spots were observed on inoculated leaves (both punctured and unwounded) about 30 hours after inoculation and typical symptoms appeared about 55 hours after inoculation (Supplementary Fig. 1 d), and the diseased leaves produced black pycnidia and orange droplet 10 days after inoculation (Supplementary Fig. 1 e). All inoculated leaves developed symptoms similar to those on the naturally infected plants in the garden and the disease incidence reached 100%, whereas the control leaves remained symptomless (Supplementary Fig. 1 f). The same fungus was re-isolated from inoculated leaves. To our knowledge, this is the first report of S. vannaccii causing leaf spot on C. crepidioides in China. So far, Stagonosporopsis vannaccii has been reported as a plant pathogenic fungus only in Brazil, causing anthracnose symptoms on pods of soybean (Crous et al. 2019). Crassocephalum crepidioides is a widely distributed weed. If S. vannaccii has strong host specificity, it is possible to be used as a biocontrol fungus to control the weed. Conversely, if the fungus has a wider host range, C. crepidioides may act as a good bridge to spread the pathogen. This study helps to deepen the understanding of S. vannaccii and its associated plant diseases.

14.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(9): 1253-1258, 2020 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-32990230

RESUMO

OBJECTIVE: To explore the correlation of plasma N-acetyl-neuraminic acid level with Thrombolysis In Myocardial Infarction (TIMI) risk score and clinical outcomes of patients with acute coronary syndrome (ACS). METHODS: We consecutively enrolled 708 consecutive patients (401 male and 307 female, mean age 63.6±10.6 years) undergoing coronary angiography in our hospital between October, 2018 and July, 2019, including 597 patients with ACS and 111 without ACS (control group). The patients with ACS group were divided into high (n=104), moderate (n=425) and low (n=68) risk groups according to their TIMI risk scores. All the participants were examined for plasma Neu5Ac level using liquid chromatography-tandem mass spectrometry and underwent coronary angiography with their Gensini scores calculated. The patients with ACS were followed up after discharge for a mean of 15 months for the occurrence of major adverse cardiac events (Mace). Binary logistic regression analysis was performed to identify the risk factors of Mace in these patients. RESULTS: Plasma Neu5Ac levels were significantly higher in ACS group than in the control group (P < 0.05). ROC curve analysis showed that plasma Neu5Ac level could assist in the diagnosis of ACS (0.648 [0.597-0.699]) with a sensitivity of 39.2% and a specificity of 86.5% at the cutoff value of 288.50 ng/mL. In the ACS patients, plasma Neu5Ac level was significantly higher in the high-risk group than in the moderate-risk and low-risk groups (P < 0.05) and could assist in the diagnosis of a high risk (0.645 [0.588-0.703]) with a sensitivity of 42.3% and a specificity of 80.1% at the cutoff value of 327.50 ng/ mL. Plasma Neu5Ac was positively correlated with age, serum uric acid, creatinine, lipoprotein a, Ddimer, C-reactive protein, MB isoform of creatine kinase and Gensini score and negatively correlated with high-density lipoprotein level. During the followup, 80 ACS patients experienced Mace, who had significantly higher plasma Neu5Ac level than those without Mace (n=517). Logistic regression analysis showed that plasma Neu5Ac level and a history of previous stroke were independent risk factors for the occurrence of Mace. CONCLUSIONS: Plasma Neu5Ac level can provide assistance in the diagnosis and risk stratification of ACS and is an independent risk factor for prognosis of ACS patients.


Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Idoso , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Ácido Úrico
15.
J Dig Dis ; 21(10): 558-565, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32761806

RESUMO

OBJECTIVE: Serrated polyps (SP) are regarded as precursor lesions of colorectal cancer (CRC). We conducted this single-center study aiming to investigate the relationship between SP and synchronous and metachronous advanced neoplasia in the Chinese population. METHODS: The data for this retrospective study were collected from the Endoscopy Center and Department of Gastroenterology of Renji Hospital, School of Medicine, Shanghai Jiao Tong University between May 2012 and May 2019. Altogether 2205 patients were pathologically confirmed with colorectal SP. RESULTS: The detection rate of SP among all polyps has gradually increased since 2014 and reached 8.74% by 2019. Among all the SP cases, 1540 (69.84%) were confirmed as having hyperplasic polyps (HP), 486 (22.04%) were having sessile serrated lesions (SSL), and 171 (7.76%) had traditional serrated adenomas (TSA). Compared with HP (2.14%), SSL and TSA were larger and more likely to be accompanied by synchronous and metachronous advanced neoplasia (6.79% and 6.08%). We next found that large SP (diameter ≥10 mm) (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.40-4.55, P = 0.002) and SSL with high-grade intraepithelial neoplasia (OR 13.85, 95% CI 3.28-58.56, P < 0.001) were associated with an increased risk of synchronous advanced neoplasia. However, we failed to find a relationship between SP and metachronous advanced neoplasia because few patients had developed metachronous advanced neoplasia. CONCLUSION: Large SP and SSL with high-grade intraepithelial neoplasia are associated with synchronous advanced neoplasia and require timely surveillance.

16.
Crit Rev Food Sci Nutr ; : 1-14, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32748625

RESUMO

Observational studies have suggested inconsistent results between maternal seafood consumption and the risk of adverse birth outcomes. We aimed to explore the possible dose-response relationship between seafood consumption during pregnancy and perinatal outcomes. A systematic search was performed with the use of PubMed, Web of Science, Embase and Cochrane Library from inception to October 27, 2019. Random-effects model was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Dose-response meta-analysis was carried out by using generalized least-squares regression and restricted cubic splines. Twenty-one studies with a total of 571641 participants were included in the analyses. A 45 g/day increment in seafood consumption was associated with a reduced risk of low birth weight (LBW) (OR: 0.65, 95% CI: 0.47 to 0.90) and small for gestational age (SGA) (OR: 0.84, 95% CI: 0.71 to 0.98). Additionally, there was a non-linear dose-response relationship between maternal seafood consumption and the risk of preterm birth (PTB), with no further benefit observed when intake above 45 g/day. The results for subtypes of seafood showed a modest J-shaped association between fatty fish and PTB, and the lowest risk was observed with the consumption of 30 g/day. In conclusion, higher total seafood consumption during pregnancy was associated with a lower risk of adverse birth outcomes, but the consumption of fatty fish should not exceed 30 grams per day. These findings could provide substantial evidence for dietary recommendations regarding seafood intake for pregnant women. This review was registered in PROSPERO (CRD42020152912).

17.
Br J Pharmacol ; 177(20): 4720-4733, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32839968

RESUMO

BACKGROUND AND PURPOSE: Dysfunction of the prefrontal cortex (PFC) is involved in the cognitive deficits in neuropsychiatric diseases, such as schizophrenia, characterized by deficient neurotransmission known as NMDA receptor hypofrontality. Thus, enhancing prefrontal activity may alleviate hypofrontality-induced cognitive deficits. To test this hypothesis, we investigated the effect of forebrain-specific suppression or pharmacological inhibition of native Kv 7/KCNQ/M-current on glutamatergic hypofrontality induced by the NMDA receptor antagonist MK-801. EXPERIMENTAL APPROACH: The forebrain-specific inhibition of native M-current was generated by transgenic expression, in mice, of a dominant-negative pore mutant G279S of Kv 7.2/KCNQ2 channels that suppresses channel function. A mouse model of cognitive impairment was established by single i.p. injection of 0.1 mg·kg-1 MK-801. Mouse models of prepulse inhibition (PPI) of acoustic startle reflex and Y-maze spontaneous alternation test were used for evaluation of cognitive behaviour. Hippocampal brain slice recordings of LTP were used to assess synaptic plasticity. Hippocampus and cortex were dissected for detecting protein expression using western blot analysis. KEY RESULTS: Genetic suppression of Kv 7 channel function in the forebrain or pharmacological inhibition of Kv 7 channels by the specific blocker XE991 enhanced PPI and also alleviated MK-801 induced cognitive decline. XE991 also attenuated MK-801-induced LTP deficits and increased basal synaptic transmissions. Western blot analysis revealed that inhibiting Kv 7 channels resulted in elevation of pAkt1 and pGSK-3ß expressions in both hippocampus and cortex. CONCLUSIONS AND IMPLICATIONS: Both genetic and pharmacological inhibition of Kv 7 channels alleviated PPI and cognitive deficits. Mechanistically, inhibition of Kv 7 channels promotes synaptic transmission and activates Akt1/GSK-3ß signalling.

18.
Gut Microbes ; 12(1): 1788900, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-32684087

RESUMO

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.

19.
Clin Nutr ; 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-32593522

RESUMO

BACKGROUND & AIMS: Emerging evidence has shown the inverse association between dietary polyphenols intake and type 2 diabetes mellitus risk, however, few studies focus on the prospective effects of polyphenols on gestational diabetes mellitus (GDM). Thus, the aim was to evaluate whether higher polyphenols intake and the intake from fruits and vegetables was correlated to a lower risk of GDM. METHODS: Dietary intake of polyphenols of women with a singleton pregnancy and without any history of diabetes were obtained by a validated food frequency questionnaire from Tongji Maternal and Child Health Cohort study. Oral glucose tolerance tests were conducted at 24-28 weeks to screen for GDM. Logistic regression models were used to evaluate the association between dietary intake of polyphenols, and the results were presented as odds ratios (ORs) with 95% confidence interval (CIs). Generalized linear models were adopted to determine the association of polyphenols intake with blood glucose concentrations, and the results were presented as coefficients (ß) with 95% CIs. RESULTS: 185 (8.3%) of 2231 pregnant women were diagnosed with GDM. The intake of total polyphenols was 319.9 (217.8-427.0) mg/d, and the intake from fruits and vegetables was 201.6 (115.3-281.8) mg/d and 63.2 (41.1-92.7) mg/d, respectively. Compared with the lowest quartile, the adjusted ORs (95% CIs) of GDM risk for women with the highest quartile of total polyphenols and flavonoids intake was 0.55 (0.30, 0.99), and 0.57 (0.32, 0.99). The adjusted ORs (95% CIs) of GDM risk was 0.55 0.51 (0.30, 0.87) (Pfor trend = 0.017) for polyphenols from fruits, 0.58 (0.34, 0.99) (Pfor trend = 0.038) for flavonoids from fruits, and 0.62 (0.38, 1.00) (Pfor trend = 0.065) for anthocyanidins from fruits comparing the highest versus lowest quartile. In addition, each 100 mg increase of total polyphenols and polyphenols from fruits was associated with 0.054 (0.008, 0.096) (P = 0.021) and 0.061 (0.012, 0.109) (P = 0.015) decrease in 2-h post-load blood glucose. No significant association was found between total polyphenols from vegetables intake and the risk of GDM. CONCLUSIONS: Higher dietary intake of total polyphenols and flavonoids and the intake from fruits was associated with lower GDM risk. This study was registered at clinicaltrials.gov as NCT03099837.

20.
Theranostics ; 10(13): 5763-5777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32483417

RESUMO

Rationale: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods: Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results: Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B-knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B. Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B (P < 0.001) in 60 human CRC tissues. Conclusion: These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B, thus driving the malignancy of CRC.

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