Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 455
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Theranostics ; 10(4): 1544-1554, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042321

RESUMO

Cancer theranostics based on glucose oxidase (GOx)-induced starvation therapy has got more and more attention in cancer management. Herein, GOx armed manganese dioxide nanosheets (denoted as MNS-GOx) were developed as cancer nanotheranostic agent for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided self-oxygenation/hyperthermia dually enhanced starvation cancer therapy. The manganese dioxide nanomaterials with different morphologies (such as nanoflowers, nanosheets and nanowires) were synthesized by a biomimetic approach using melanin as a biotemplate. Afterwards, the manganese dioxide nanosheets (MNS) with two sides and large surface area were selected as the vehicle to carry and deliver GOx. The as-prepared MNS-GOx can perform the circular reaction of glucose oxidation and H2O2 decomposition for enhanced starvation therapy. Moreover, the catalytic activity of GOx could be further improved by the hyperthermia of MNS-GOx upon near-infrared laser irradiation. Most intriguingly, MNS-GOx could achieve "turn-on" MR imaging and "turn-off" PA imaging simultaneously. The theranostic capability of MNS-GOx was evaluated on A375 tumor-bearing mice with all tumor elimination. Our findings integrated molecular imaging and starvation-based synergistic cancer therapy, which provided a new platform for cancer nanotheranostics.

2.
Pancreatology ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31941586

RESUMO

OBJECTIVES: The effectiveness of enucleation in treatment for low-grade (G1, G2) small (≤2 cm) non-functional pancreatic neuroendocrine tumors (sNF-pNETs) remains controversial. This study investigated short- and long-term outcome of enucleation comparing with regular pancreatectomy in patients with sNF-pNETs. METHODS: The clinical data of patients with sNF-pNETs who underwent surgery in our hospital from January 2000 to December 2017 were retrospectively collected. Short- and long-term outcomes of two operations were analyzed. The propensity score matching (PSM) was performed to reduce potential selection bias. RESULTS: A total of 123 patients with sNF-pNETs were enrolled with 62 males, 69 G1, and median age was 56.91 ± 10.04 years old. During the follow-up period (mean 87 ± 58.1 months), 9(7.32%) disease progressed (recurrence or metastasis) and 2 died (1.62%), 5-years OS was 100%, 5-years DFS was 91.4%. Both lymph node metastasis (p = 0.117) and pathological grade (p = 0.050) were not prognostic factors for sNF-pNETs. The propensity score-matched cohort comprised 27 patients with enucleation and 44 patients with regular pancreatectomy. Enucleation was noninferior to regular pancreatectomy in terms of DFS, before or after PSM. The surgical duration (P < 0.01) and blood loss (P < 0.01) significantly decreased in enucleation compared with regular pancreatectomy. The other postoperative complications tended to occur in regular pancreatectomy than in enucleation, but no statistically significant difference (all p > 0.05). CONCLUSION: Enucleation seems to be an effective option for the treatment of sNF-pNETs with a lower total rate of postoperative complications and similar long-term prognosis, compared with regular pancreatectomy.

3.
BMC Genomics ; 21(1): 4, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898486

RESUMO

BACKGROUND: Somatic embryogenesis (SE) is a process of somatic cells that dedifferentiate to totipotent embryonic stem cells and generate embryos in vitro. Longan SE has been established and wildly used as model system for studying embryogenesis in woody plants, SE-related genes had been characterized. In spite of that, a comprehensive overview of SE at a molecular level is still absent. To understand the molecular mechanisms during longan SE, we examined the transcriptome changes by using Illumina HiSeq from the four distinct developmental stages, including non-embryogenic callus (NEC), embryogenic callus (EC), incomplete compact pro-embryogenic cultures (ICpEC), globular embryos (GE). RESULTS: RNA-seq of the four samples generated a total of 243.78 million high quality reads, approximately 81.5% of the data were mapped to longan genome. The cDNA libraries of NEC, EC, ICpEC and GE, generated 22,743, 19,745, 21,144, 21,102 expressed transcripts, 1935, 1710, 1816, 1732 novel transcripts, 2645, 366, 505, 588 unique genes, respectively. Comparative transcriptome analysis showed that a total of 10,642, 4180, 5846 and 1785 genes were differentially expressed in the pairwise comparisons of NEC_vs_EC, EC_vs_ICpEC, EC_vs_GE, ICpEC_vs_GE, respectively. Among them, plant hormones signalling related genes were significantly enriched, especially the auxin and cytokinin signalling components. The transcripts of flavonoid biosynthesis related genes were mainly expressed in NEC, while fatty acid biosynthesis related genes mainly accumulated in early SE. In addition, the extracelluar protein encoding genes LTP, CHI, GLP, AGP, EP1 were related to longan SE. Combined with the FPKM value of longan nine tissues transcription, 27 SE specific or preferential genes (LEC1, LEC1-like, PDF1.3, GH3.6, AGL80, PIN1, BBM, WOX9, WOX2, ABI3, et al.) and 28 NEC preferential genes (LEA5, CNOT3, DC2.15, PR1-1, NsLTP2, DIR1, PIP1, PIP2.1, TIP2-1, POD-P7 and POD5 et al.) were characterized as molecular markers for longan early SE. qRT-PCR validation of SE-related genes showed a high correlation between RNA-seq and qRT-PCR data. CONCLUSION: This study provides new insights into the role of the transcriptome during early SE in longan. Differentially expressed genes reveal that plant hormones signalling, flavonoid and fatty acid biosynthesis, and extracelluar protein related genes were involved in longan early SE. It could serve as a valuable platform resource for further functional studies addressing embryogenesis in woody plants.

4.
Pediatr Transplant ; 24(2): e13618, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944495

RESUMO

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×108 /mL before MSC infusion and 2.67 (0-56.3) ×108 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.

5.
J Cell Biochem ; 121(3): 2225-2235, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31692053

RESUMO

PURPOSE: Long-chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth-stasis specific transcript 5 (GAS5) on triple-negative breast cancer (TNBC). METHODS: Quantitative real-time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a-5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo. RESULTS: In this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum-free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR-378 could directly bind to each other. Moreover, the miR-378a-5p target of SUFU could promote lncRNA GAS5-induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA-231R could enhance the sensitivity of TNBC to PTX. CONCLUSION: The above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR-378a-5p/SUFU signaling.

6.
Inorg Chem ; 59(1): 193-197, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31858791

RESUMO

Two pairs of enantiomeric 3d-4f metal clusters, [Co2Ln[(R)/(S)-L]4]·Cl5·(H2O)2·CH3OH·CH3CH2OH [Co2Ln; Ln = Gd (1S and 1R), Dy (2S and 2R)], were synthesized by the reaction of chiral Schiff-base ligand (R)/(S)-3-[(2-hydroxybenzylidene) amino]propane-1,2-diol [(R)/(S)-HL] with CoCl2·6H2O and LnCl3·6H2O. The circular dichroism spectra of (S)/(R)-Co2Ln display a mirror-symmetry effect with seven peaks at 210-800 nm, which can be ascribed to π-π* transitions, exciton coupling, charge-transfer transitions between ligands and Co3+, and characteristic d-d transitions of Co3+ ions. Interestingly, the chiral Co2Ln metal clusters display strong magnetic circular dichroism signals at room temperature. This work suggests that the chiromagnetic metal cluster is expected to show a strong magnetooptical response.

7.
Bioresour Technol ; 296: 122290, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677404

RESUMO

Three-dimensional biofilm electrode reactors (3D-BERs) with high treatment efficiency were constructed to treat wastewater containing sulfadiazine (SDZ) and ciprofloxacin (CIP) coexposure with Zinc (Zn). The results showed that coexposure to target antibiotics and Zn increased the absolute and relative abundances of target antibiotic resistance genes (ARGs). Additionally, the target ARG abundances were higher on cathode of 3D-BER compared with ordinary anaerobic reactor while the abundances of total ARGs were decreased in the effluent. Meanwhile, redundancy analysis results revealed that the composition of bacteria carrying ARGs was greatly influenced in the cathode by the accumulation of Zn and antibiotic, which dominated the changes of ARG abundances. Additionally, ARGs with their host bacteria revealed by network analysis were partially deposited on electrode substrates when being removed from wastewater. Thus, 3D-BER exhibits capability of simultaneously eliminating antibiotic and Zn, and greatly reduces the risks of ARGs spread.


Assuntos
Antibacterianos , Ciprofloxacino , Bactérias , Biofilmes , Resistência Microbiana a Medicamentos , Eletrodos , Genes Bacterianos , Características de Residência , Sulfadiazina , Águas Residuárias , Zinco
9.
World J Clin Cases ; 7(22): 3832-3837, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31799311

RESUMO

BACKGROUND: Hilar masses with stenosis of the bronchus occur mainly due to malignant diseases, such as lung cancer. Hilar masses resulting from invasive aspergillosis are extremely rare and occur mostly in severely immunosuppressed patients. CASE SUMMARY: In the current case report, we have documented a unique case of invasive aspergillosis presenting as a mass in the hilum and bronchial stenosis under bronchoscopy mimicking lung cancer in a 54-year-old man with diabetes mellitus. The histological analysis of bronchial membrane biopsy demonstrated fungal elements of 45° branching hyphae with positive Periodic Acid-Schiff and Grocott staining. After 3 mo of antifungal therapy, the symptoms, computed tomography scan and bronchoscopy manifestations all showed improvement. CONCLUSION: We highlight that clinicians should consider a diagnosis of invasive aspergillosis when radiological examination shows pseudotumor appearance in diabetes mellitus patients.

10.
J Physiol Biochem ; 75(4): 607-618, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31786730

RESUMO

Previous studies have shown that stromal interaction molecule1 (STIM1)-mediated store-operated Ca2+ entry (SOCE) contributes to intracellular Ca2+ accumulation in H9C2 cells subjected to hypoxia/reoxygenation(H/R) injury. The aim of the present study was to investigate the effect of resveratrol on STIM1-mediated intracellular Ca2+ accumulation and subsequent cell death in the context of myocardial ischemia/reperfusion (I/R) injury. C57 BL/6 mice were fed with either saline or resveratrol (50 mg/kg daily for 2 weeks) and then subjected to myocardial I/R injury. TTC/Evans Blue staining and TUNEL assay were performed to quantify the infarct size and apoptosis index. The cardiac function was evaluated by echocardiography. Neonatal rat ventricular cardiomyocytes (NRVCs) underwent hypoxia/reoxygenation (H/R) to establish the in vitro model. To achieve over-expression, NRVCs were transfected with STIM1-adenovirus vector. Apoptosis was analyzed by TUNEL assay. Cell viability was measured using MTS assay and cell necrosis was determined by LDH release assay. Intracellular Ca2+ concentration was detected by laser scanning confocal microscopy using a Fluo-3AM probe. Resveratrol significantly reduced apoptosis, decreased infarct size, and improved cardiac function in mice subjected to myocardial I/R injury. In NRVCs, resveratrol also downregulated STIM1 expression accompanied by decreased intracellular Ca2+ accumulation elicited by H/R injury. In addition, resveratrol reduced cell apoptosis, upregulated the Bcl-2, decreased Bax, and cleaved caspase-3 expression. Furthermore, the effects of resveratrol on STIM1-mediated intracellular Ca2+ accumulation, apoptotic proteins, and H/R-induced cell injury were exacerbated by STIM1 over-expression and were partly abolished by SOCE inhibitor SKF96365 in NRVCs in vitro. Our findings demonstrate that resveratrol exerts anti-apoptotic activity and improves cardiac functional recovery following myocardial I/R by inhibiting STIM1-induced intracellular Ca2+ accumulation.

11.
J Neuroinflammation ; 16(1): 249, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796106

RESUMO

BACKGROUND: Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. METHODS: Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. RESULTS: LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. CONCLUSIONS: Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31876352

RESUMO

OBJECTIVES: To improve the prognostic value of the age, creatinine, and ejection fraction (ACEF) score following percutaneous coronary intervention (PCI) by integrating the residual SYNTAX score (rSS). BACKGROUND: ACEF score was proposed for predicting the operative mortality risk in elective cardiac operations and has been validated in numerous studies. However, it does not incorporate coronary lesion-based variables for risk assessment of patients who undergo PCI. METHODS: Overall, 10,072 patients who underwent PCI at our hospital in 2013 were enrolled. The endpoint was 2-year cardiac death after PCI, defined as death that was not attributed to a non-cardiac cause. ACEF-rSS was constructed with incremental weights attributed to the ACEF score and rSS according to their estimated coefficients. RESULTS: 2-year cardiac death occurred in 63 patients (0.63%). In multivariable analyses, the ACEF score and rSS > 8 were independently associated with the risk of cardiac death. ACEF-rSS was computed as age (years)/ejection fraction (%) + 1 (if creatinine ≥2.0 mg/dl) + 1 (if rSS >8). The discrimination of ACEF-rSS was significantly better than that of the ACEF score based on receiver operating characteristic (ROC) curve analysis and integrated discrimination improvement (IDI) (C-statistics = 0.835 vs. 0.776 for ACEF-rSS and ACEF score, respectively, p = .029; IDI = 0.014, p < .001). Compared with all other SYNTAX-derived risk scores, ACEF-rSS had significantly better discrimination ability based on ROC curve analysis, net reclassification improvement, and IDI. CONCLUSIONS: Combining the ACEF score with rSS to produce the ACEF-rSS enhanced the predictive ability for long-term cardiac mortality.

13.
Clin Pharmacol Ther ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31868917

RESUMO

Drug safety is a severe clinical pharmacology and toxicology problem that has caused immense medical and social burdens every year. Regretfully, there still misses a reproducible method to assess drug safety systematically and quantitatively. In this study, we developed an advanced machine learning model for de novo drug safety assessment by solving the multilayer drug-gene-adverse drug reaction (ADR) interaction network. For the first time, the drug safety was assessed in a broad landscape of 1,156 distinct ADRs. We also designed a parameter ToxicityScore to quantify the overall drug safety. Moreover, we determined association strength for every 3,807,631 gene-ADR interactions, which clues mechanistic exploration of ADRs. For convenience, we deployed the model as a web service ADRAlert-gene at http://www.bio-add.org/ADRAlert/. In summary, this study offers insights into prioritizing safe drug therapy. It helps to reduce the attrition rate of new drug discovery by providing reliable ADR profile in early pre-clinical stage.

14.
Inorg Chem ; 58(22): 15401-15409, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31674179

RESUMO

A new iron-base superconductor SmFFeAs is synthesized via solid-state metathesis reaction by using SmFCl and LiFeAs as precursors. The compound crystallized in the tetragonal ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters of a = 3.9399(0) Å and c = 8.5034(1) Å. The superconducting diamagnetic transition occurs at 56 K for the parent compound, which confirmed by the resistivity and magnetic susceptibility. The appearance of superconductivity without extrinsic doping could be ascribed to the self-doping owing to the mixed valence of Sm ions. The as-synthesized SmFFeAs serves as a new self-doped parent compound for oxygen-free high-critical-temperature (high-Tc) superconductors.

15.
Math Biosci Eng ; 16(6): 7375-7383, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31698617

RESUMO

The heparan sulfate proteoglycan agrin is known to accumulate in the context of hepatocellular carcinoma (HCC). Agrin is important for neoangiogenesis in HCC tissues, and is incorporated into newly formed vasculature, but exactly how agrin contributes to the pathology of HCC remains to be fully defined. We therefore examined the clinical relevance of agrin as it pertains to HCC progression and prognosis using tissue sections from a total of 313 HCC patients. We found that agrin expression was detectable in more HCC samples (25.4% vs. 77.1%; P < 0.05) compared to normal tissue controls. Agrin expression was notably linked to tumor size (P = 0.041) and metastasis (P = 0.034). The recurrence free survival rate of agrin-positive HCC patients was considerably lower than that of agrin-negative patients (P = 0.001). We further confirmed HCC survival to be independently correlated with tumor size, metastasis, microvascular invasion and edmondson Grade via a Cox regression analysis. Upregulation of Agrin may play a crucial role in HCC progression. Together our results suggest that Agrin has the potential to be used as a prognostic indicator in predicting HCC patient outcomes.

16.
Infect Drug Resist ; 12: 3189-3195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632104

RESUMO

Background: Patients with high-titer anti-IFN-γ autoantibodies present disseminated non-tuberculous mycobacterial (NTM) and other opportunistic infections. Due to its rare occurrence and non-specific symptoms, this syndrome is difficult to diagnose during early disease stages. Here, we report a case with high-concentrations of serum anti-IFN-γ autoantibodies who presented with disseminated Talaromyces marneffei and NTM disease accompanied Sweet's syndrome. Case presentation: A 62-year-old Chinese woman with no previous history was admitted to our hospital in August 2016 due to intermittent fever for 2 years, left chest wall redness, and swelling for 3 months. During hospitalization, the patient was confirmed with disseminated T. marneffei and successfully treated with antifungal therapy. In July 2017, upon second admission, Mycobacterium avium intracellular (MAC) pulmonary infection was established after positive cultures from the right lung tissue. The patient failed treatment after 1 month of anti-NTM therapy due to side effects. In May 2018, she was confirmed as having disseminated MAC disease accompanied by hand rashes, which was considered as Sweet's syndrome. High-level anti-IFN-γ antibodies in the patient serum were detected upon comparison with normal controls (2.85-fold increase). Following anti-NTM therapy, both symptoms and pulmonary infiltration gradually improved, and joint destruction and lymphadenitis remained. Conclusions: Patients with anti-interferon-γ autoantibodies should be considered for severe, recurrent infections in adults in the absence of other known risk factors. Sweet's syndrome is a common skin manifestation of the syndrome.

17.
Front Microbiol ; 10: 2185, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632359

RESUMO

Probiotics have been widely used in maintaining intestinal health and one of their benefits is to enhance host antioxidant capacity. However, the involved molecular mechanisms require further investigated. Autophagy is a self-protection process in response to diverse stresses. We hypothesized that probiotics could modulate intestinal autophagy to alleviate oxidative stress. Sprague-Dawley (SD) rats were orally administered Bacillus SC06 or SC08 daily for 24 days and thereafter received an intraperitoneal injection of diquat (DQ) to induce oxidative stress. We found that rats administered Bacillus SC06 showed more significant intestinal tissue repair and antioxidant properties than those administered SC08, which suggests a strain-specific effect of probiotics. Moreover, SC06 alleviated apoptosis by regulating the expression of Bcl2, Bax and cleaved caspase-3. Further investigations revealed that SC06 triggered autophagy, indicated by the upregulation of LC3 and Beclin1 and the degradation of p62 in rat jejunum and IEC-6 cells. Preincubation with autophagy inhibitor 3-methyladenine (3-MA) significantly aggravated reactive oxygen species (ROS) production and apoptotic cell formation. Furthermore, we demonstrated that p38 MAPK (mitogen-activated protein kinase), not AKT (alpha serine/threonine kinase)/mTOR (mammalian target of rapamycin), was involved in SC06-induced autophagy. Taken together, Bacillus SC06 can alleviate oxidative stress-induced disorders and apoptosis via p38-mediated autophagy. The above findings highlight a novel mechanism underlying the beneficial effects of probiotics as functional food and provide a new perspective on the prevention and treatment of oxidative damages.

18.
J Agric Food Chem ; 67(45): 12382-12392, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31635461

RESUMO

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a promising target for herbicide discovery. Search for new compounds with novel chemotypes is a key objective for agrochemists. Here, we describe the discovery and systematic SAR-based structure optimization of novel N-isoxazolinylphenyltriazinones 5-9 as PPO inhibitors. The in vivo herbicidal activity and in vitro Nicotiana tabacum PPO (NtPPO) inhibitory activity were explored in detail. A number of the new synthetic compounds displayed strong PPO inhibitory activity with Ki values in the nanomolar range. Some compounds exhibited excellent and broad-spectrum weed control at the rate of 9.375-37.5 g ai/ha by postemergence application and showed improved monocotyledonous weed control compared to saflufenacil. Most promisingly, ethyl 3-(2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluorophenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate, 5a, with a Ki value of 4.9 nM, displayed over 2- and 6-fold higher potency than saflufenacil (Ki = 10 nM) and trifludimoxazin (Ki = 31 nM), respectively. Moreover, 5a showed excellent and broad-spectrum weed control against 32 kinds of weeds at 37.5-75 g ai/ha. Rice exhibited relative tolerance to 5a at 150 g ai/ha by postemergence application, indicating that 5a could be a potential herbicide candidate for weed control in paddy fields.


Assuntos
Inibidores Enzimáticos/farmacologia , Herbicidas/química , Herbicidas/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Protoporfirinogênio Oxidase/antagonistas & inibidores , Descoberta de Drogas , Inibidores Enzimáticos/química , Cinética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Daninhas/química , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/enzimologia , Protoporfirinogênio Oxidase/química , Protoporfirinogênio Oxidase/metabolismo , Relação Quantitativa Estrutura-Atividade , Tabaco/química , Tabaco/efeitos dos fármacos , Tabaco/enzimologia , Controle de Plantas Daninhas
19.
Front Genet ; 10: 966, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649733

RESUMO

Cancer subtypes can improve our understanding of cancer, and suggest more precise treatment for patients. Multi-omics molecular data can characterize cancers at different levels. Up to now, many computational methods that integrate multi-omics data for cancer subtyping have been proposed. However, there are no consistent criteria to evaluate the integration methods due to the lack of gold standards (e.g., the number of subtypes in a specific cancer). Since comprehensive evaluation and comparison between different methods serves as a useful tool or guideline for users to select an optimal method for their own purpose, we develop a scalable platform, CEPICS, for comprehensively evaluating and comparing multi-omics data integration methods in cancer subtyping. Given a user-specified maximum number of subtypes, k-max, CEPICS provides (1) cancer subtyping results using up to five built-in state-of-the-art integration methods under the number of subtypes from two to k-max, (2) a report including the evaluation of each user-selected method and comparisons across them using clustering performance metrics and clinical survival analysis, and (3) an overall analysis of subtyping results by different methods representing a robust cancer subtype prediction for samples. Furthermore, users can upload subtyping results of their own methods to compare with the built-in methods. CEPICS is implemented as an R package and is freely available at https://github.com/GaoLabXDU/CEPICS.

20.
Int J Behav Nutr Phys Act ; 16(1): 95, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665040

RESUMO

BACKGROUND: Childhood obesity is a serious public health concern. School-based interventions hold great promise to combat the rising trend of childhood obesity. This systematic review aimed to assess the overall effects of school-based obesity prevention interventions, and to investigate characteristics of intervention components that are potentially effective for preventing childhood obesity. METHODS: We systematically searched MEDLINE, CENTRAL and Embase databases to identify randomized- or cluster randomized- controlled trials of school-based obesity interventions published between 1990 and 2019. We conducted meta-analyses and subgroup analyses to determine the overall effects of obesity prevention programs and effect differences by various characteristics of intervention components on body mass index (BMI) or BMI Z-score of children. RESULTS: This systematic review included a total of 50 trials (reported by 56 publications). Significant differences were found between groups on BMI (- 0.14 kg/m2 (95% confidence interval: - 0.21, - 0.06)) and BMI Z-score (- 0.05 (- 0.10, - 0.01)) for single-component interventions; significant differences were also found between groups on BMI (- 0.32 (- 0.54, - 0.09) kg/m2) and BMI Z-score (- 0.07 (- 0.14, - 0.001)) for multi-component interventions. Subgroup analyses consistently demonstrated that effects of single-component (physical activity) interventions including curricular sessions (- 0.30 (- 0.51, - 0.10) kg/m2 in BMI) were stronger than those without curricular sessions (- 0.04 (- 0.17, 0.09) kg/m2 in BMI); effects of single-component (physical activity) interventions were also strengthened if physical activity sessions emphasized participants' enjoyment (- 0.19 (- 0.33, - 0.05) kg/m2 in BMI for those emphasizing participants' enjoyment; - 0.004 (- 0.10, 0.09) kg/m2 in BMI for those not emphasizing participants' enjoyment). The current body of evidence did not find specific characteristics of intervention components that were consistently associated with improved efficacy for multi-component interventions (P > 0.05). CONCLUSIONS: School-based interventions are generally effective in reducing excessive weight gain of children. Our findings contribute to increased understandings of potentially effective intervention characteristics for single-component (physical activity) interventions. The impact of combined components on effectiveness of multi-component interventions should be the topic of further research. More high-quality studies are also needed to confirm findings of this review.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA