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1.
Int J Pharm ; : 118730, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31705972

RESUMO

Poor water solubility and low bioavailability hinder the clinical application of about 70% of newly synthesized compounds. Nanocrystal technology has become a preferred way to improve bioavailability by improving solubility. However, it remains challenging to produce nanocrystals with ultra-small particle sizes to further enhance the extent of bioavailability. Herein, we constructed ultra-small puerarin nanocrystals (Pue-NCs) (20-40 nm) via formation of hydrogen bond during HPH. We confirmed the formation of hydrogen bonds by 1H NMR and FTIR, and observed the distribution of polymer chains by SEM and TEM. The absorption mechanisms were studied in Caco-2 cell monolayers, and the results showed that the major transport mechanism for puerarin was passive diffusion, meanwhile, for Pue-NCs, the passive transport and micropinocytosis-mediated endocytosis coexisted. The absolute bioavailability of Pue-NCs was 35.28%, which was 11.54 folds compared to that of puerarin. Therapeutic equivalence was demonstrated between Pue-NCs and puerarin injection at 50 mg/kg and 15 mg/kg, respectively, in isoproterenol-induced myocardial ischemia model. This study provides a novel strategy for preparing ultra-small nanocrystals by HPH to increase bioavailability of poorly soluble drugs.

2.
J Neuroinflammation ; 16(1): 214, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722723

RESUMO

BACKGROUND: Neonatal hypoxic-ischemic brain damage (HIBD), a leading cause of neonatal mortality, has intractable sequela such as epilepsy that seriously affected the life quality of HIBD survivors. We have previously shown that ion channel dysfunction in the central nervous system played an important role in the process of HIBD-induced epilepsy. Therefore, we continued to validate the underlying mechanisms of TRPV1 as a potential target for epilepsy. METHODS: Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. Primarily cultured astrocytes were used to assess the expression of TRPV1, glial fibrillary acidic protein (GFAP), cytoskeletal rearrangement, and inflammatory cytokines by using Western blot, q-PCR, and immunofluorescence. Furthermore, brain electrical activity in freely moving mice was recorded by electroencephalography (EEG). TRPV1 current and neuronal excitability were detected by whole-cell patch clamp. RESULTS: Astrocytic TRPV1 translocated to the membrane after OGD. Mechanistically, astrocytic TRPV1 activation increased the inflow of Ca2+, which promoted G-actin polymerized to F-actin, thus promoted astrocyte migration after OGD. Moreover, astrocytic TRPV1 deficiency decreased the production and release of pro-inflammatory cytokines (TNF, IL-6, IL-1ß, and iNOS) after OGD. It could also dramatically attenuate neuronal excitability after OGD and brain electrical activity in HIBD mice. Behavioral testing for seizures after HIBD revealed that TRPV1 knockout mice demonstrated prolonged onset latency, shortened duration, and decreased seizure severity when compared with wild-type mice. CONCLUSIONS: Collectively, TRPV1 promoted astrocyte migration thus helped the infiltration of pro-inflammatory cytokines (TNF, IL-1ß, IL-6, and iNOS) from astrocytes into the vicinity of neurons to promote epilepsy. Our study provides a strong rationale for astrocytic TRPV1 to be a therapeutic target for anti-epileptogenesis after HIBD.

3.
Biotechnol Lett ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31720977

RESUMO

Xylanosomes, also known as hemicellulosomes, are hemicellulose-degrading nano-scale multienzyme complexes produced by some Firmicutes, Actinobacteria, and Fungi. Here we report the isolation of the MECs produced by Actinotalea fermentas JCM9966, as well as the functional studies and subunit structure revealed by proteomic identifications. The isolated MECs here shows similar particle size with the xylanosomes produced by C. cellulans F16, have several conserved multi-domain proteins, while differ significantly in enzymatic activities and low molecular weight subunit compositions, indicating diverse capability as well as bias in degrading hemicelluloses.

4.
Medicine (Baltimore) ; 98(43): e17537, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651856

RESUMO

Neutrophil-to-lymphocyte ratio (NLR) serves as a strong prognostic indicator for patients suffering from various diseases. Neutrophil activation promotes the recruitment of a number of different cell types that are involved in acute and chronic inflammation and are associated with cancer treatment outcome. Measurement of NLR, an established inflammation marker, is cost-effective, and it is likely that NLR can be used to predict the development of metabolic syndrome (MS) at an early stage. MS scores range from 1 to 5, and an elevated MS score indicates a greater risk for MS. Monitoring NLR can prevent the risk of MS.A total of 34,013 subjects were enrolled in this study. The subjects (score 0-5) within the 6 groups were classified according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and all anthropometrics, laboratory biomarkers, and hematological measurements were recorded. For the 6 groups, statistical analysis and receiver operating characteristic (ROC) curves were used to identify the development of MS.Analysis of the ROC curve indicated that NLR served as a good predictor for MS. An MS score of 1 to 2 yielded an acceptable discrimination rate, and these rates were even higher for MS scores of 3 to 5 (P < .001), where the prevalence of MS was 30.8%.NLR can be used as a prognostic marker for several diseases, including those associated with MS.


Assuntos
Linfócitos/metabolismo , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Neutrófilos/metabolismo , Medição de Risco/métodos , Adulto , Biomarcadores/sangue , Feminino , Humanos , Contagem de Linfócitos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
5.
Int J Biol Sci ; 15(9): 1977-1992, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523198

RESUMO

Background: Currently, there are no molecular biomarkers for the early detection of non-small-cell lung cancer (NSCLC). This study focused on identifying RNAs found on tumor-educated blood platelets (TEPs) for detecting stage I NSCLC. Methods: Platelet RNAs, isolated from the blood of 9 patients with NSCLC (stages I and II) and 8 healthy controls, were analyzed using RNA-seq. ITGA2B was selected as a candidate marker. Two different Polymerase Chain Reactions (PCR) were used to measure ITGA2B in platelet samples from healthy controls (n = 150), patients with NSCLC (n = 243), and patients with benign pulmonary nodules (n = 141) in two cohorts. Results: Platelet ITGA2B levels were significantly higher (p < 0.001) in patients with NSCLC than in all controls. The diagnostic accuracy of ITGA2B was area under the curve (AUC) of 0.922 [95% confidence interval (CI), 0.892-0.952], sensitivity of 92.8%, and specificity of 78.6% in the test cohort and 0.888, 91.2%, and 56.5% in the validation cohort for NSCLC by quantitative real time PCR (q-PCR). Furthermore, ITGA2B maintained diagnostic accuracy for patients with NSCLC using Droplet Digital PCR (ddPCR) and the other type of internal control, Ribosomal Protein L32 (RPL32) [ddPCR: 0.967 (0.929-1.000) and RPL32: 0.847(0.773-0.920)]. A nomogram incorporating ITGA2B, carcinoembryonic antigen (CEA) and stage could predict the overall survival (C-index = 0.756). Conclusions: TEP ITGA2B is a promising marker to improve identification of patients with stage I NSCLC and differentiate malignant from benign lung nodules.

6.
Bioorg Chem ; 91: 103129, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374522

RESUMO

Cyclopianes, featuring a highly rigid 6/5/5/5-fused tetracyclic framework, are structurally unique and biologically significant and belong to a rarely reported diterpenoid family. Chemical investigation of an EtOAc extract of a deep-sea-derived Penicillium sp. led to the isolation of three new cyclopiane diterpenes, namely, conidiogenols C-D (1-2) and conidiogenone L (3). The structures were determined by extensive analyses of the spectroscopic data in association with ECD calculations and chemical conversion for configurational assignments. Compound 1 represents the second example of cyclopianes bearing a hydroxyl group at C-13. Compound 2, the third example of conidiogenols, possesses a distinct α-oriented 1-hydroxy group relative to other analogues. The bioassay study demonstrated that compounds 2 and 4-6 exhibited moderate inhibitory effects against five esophageal cancer cell lines with IC50 values ranging from 25 to 55 µM. The cytotoxicities of all compounds toward esophageal cancer cell lines were evaluated for the first time.

7.
BMJ Open ; 9(8): e027193, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375608

RESUMO

INTRODUCTION: Methamphetamine misuse is classified as a 'likely' risk factor for pulmonary arterial hypertension (PAH). Nevertheless, the actual prevalence of and a screening strategy for PAH in methamphetamine users have not been established. We plan to study the prevalence of PAH and identify its independent risk factors among methamphetamine users. METHODS AND ANALYSIS: The Screening Of Pulmonary Hypertension in Methamphetamine Abusers (SOPHMA) study will be a multicentre, cross-sectional screening study that will involve substance abuse clinics, hospitals and rehabilitation facilities in Hong Kong that cater to more than 20 methamphetamine users. A total of 400 patients who (1) are ≥18 years at enrolment; (2) report methamphetamine use in the last 2 years; (3) are diagnosed with methamphetamine use disorder; and (4) voluntarily agree to participate by providing written informed consent will be included. Patients will undergo standard echocardiography-based PAH screening procedures recommended for those with systemic sclerosis. Right heart catheterisation will be offered to participants with intermediate or high echocardiographic probability of PAH. For participants with a low echocardiographic probability of PAH, rescreening will be performed within 1 year. The primary measure will be the prevalence of PAH in methamphetamine users. The secondary measures will be the risk factors and a prediction model for PAH in methamphetamine users. ETHICS AND DISSEMINATION: The SOPHMA study has been approved by the institutional review board. The findings of this study will provide the necessary evidence to establish universal guidelines for screening of PAH in methamphetamine users. Our results will be disseminated through immediate feedback to study participants, press release to the general public, as well as presentation in medical conferences and publications in peer-reviewed journals to healthcare providers and academia worldwide.

8.
Mar Drugs ; 17(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31163670

RESUMO

Three new butenolide derivatives, namely aspernolides N-P (1-3), together with six known analogues (4-9), were isolated from the ethyl acetate (EtOAc) extract of the deep sea-derived fungus Aspergillus terreus YPGA10. The structures of compounds 1-3 were determined on the basis of comprehensive analyses of the nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data, and the absolute configurations of 1 and 2 were determined by comparisons of experimental electronic circular dichroism (ECD) with calculated ECD spectra. Compound 1 represents the rare example of Aspergillus-derived butenolide derivatives featured by a monosubstituted benzene ring. Compounds 6-9 exhibited remarkable inhibitory effects against α-glucosidase with IC50 values of 3.87, 1.37, 6.98, and 8.06 µM, respectively, being much more active than the positive control acarbose (190.2 µM).


Assuntos
4-Butirolactona/análogos & derivados , Organismos Aquáticos/química , Aspergillus/química , Inibidores de Glicosídeo Hidrolases/farmacologia , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Acetatos/química , Dicroísmo Circular , Ativação Enzimática/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
9.
Int J Cancer ; 145(10): 2873-2883, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31044420

RESUMO

We analyzed the number of circulating tumor cells (CTCs) and Epstein-Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first-line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first-line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first-line chemotherapy was associated with significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first-line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first-line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.

10.
Plant Physiol Biochem ; 141: 40-50, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128562

RESUMO

Agrobacterium-mediated soybean transformation has been greatly improved in recent years, however the transformation efficiency is still low and highly genotype-dependent when compared to other species. Here, we characterized seventeen soybean genotypes based on their genetic transformation efficiencies, i.e., high and low, during Agrobacterium-mediated transformation. To reveal the molecular basis of this transformation difference, we constructed a highly efficient transient transgene expression system using soybean cotyledon protoplasts and then assess the methylation levels of promoter and coding regions of an EYFP (enhanced yellow fluorescent protein) gene introduced into the protoplast cultures of various soybean genotypes using BSP (bisulfite sequencing PCR). Increased methylation was found to be associated with the considerably decreased transfection efficiency (as percentage of EYFP fluorescent protoplasts) in low-efficacy genotypes as compared with those in high-efficacy on three DAT (day after transfection). 5-Azacytidine (5-Azac), a demethylating reagent commonly applied in epigenetic researches, significantly improved the transient transfection efficiency and transgene expression level in low-efficiency genotypes. Furthermore, the shoot regeneration efficiency in low-efficiency genotypes was substantially increased by 5-Azac treatment in an Agrobacterium-mediated soybean transformation system. Taken together, we concluded that lower methylation level in transgene contributed to enhanced shoot regeneration in Agrobacterium-mediated soybean transformation.


Assuntos
Agrobacterium tumefaciens/genética , Azacitidina/farmacologia , Técnicas de Transferência de Genes , Brotos de Planta/efeitos dos fármacos , Soja/efeitos dos fármacos , Cotilédone/genética , Metilação de DNA , Fabaceae/genética , Genes de Plantas , Genótipo , Metilação , Peptídeo Hidrolases/metabolismo , Plantas Geneticamente Modificadas/genética , Protoplastos , Regeneração , Análise de Sequência de DNA , Soja/genética , Transfecção , Transformação Genética , Transgenes
11.
J Neuroinflammation ; 16(1): 114, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142341

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication with high incidence in both advanced and developing countries. Children surviving from HIE often have severe long-term sequela including cerebral palsy, epilepsy, and cognitive disabilities. The severity of HIE in infants is tightly associated with increased IL-1ß expression and astrocyte activation which was regulated by transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel in the TRP family. METHODS: Neonatal hypoxic ischemia (HI) and oxygen-glucose deprivation (OGD) were used to simulate HIE in vivo and in vitro. Primarily cultured astrocytes were used for investigating the expression of glial fibrillary acidic protein (GFAP), IL-1ß, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and activation of the nucleotide-binding, oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome by using Western blot, q-PCR, and immunofluorescence. Brain atrophy, infarct size, and neurobehavioral disorders were evaluated by Nissl staining, 2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and neurobehavioral tests (geotaxis reflex, cliff aversion reaction, and grip test) individually. RESULTS: Astrocytes were overactivated after neonatal HI and OGD challenge. The number of activated astrocytes, the expression level of IL-1ß, brain atrophy, and shrinking infarct size were all downregulated in TRPV1 KO mice. TRPV1 deficiency in astrocytes attenuated the expression of GFAP and IL-1ß by reducing phosphorylation of JAK2 and STAT3. Meanwhile, IL-1ß release was significantly reduced in TRPV1 deficiency astrocytes by inhibiting activation of NLRP3 inflammasome. Additionally, neonatal HI-induced neurobehavioral disorders were significantly improved in the TRPV1 KO mice. CONCLUSIONS: TRPV1 promotes activation of astrocytes and release of astrocyte-derived IL-1ß mainly via JAK2-STAT3 signaling and activation of the NLRP3 inflammasome. Our findings provide mechanistic insights into TRPV1-mediated brain damage and neurobehavioral disorders caused by neonatal HI and potentially identify astrocytic TRPV1 as a novel therapeutic target for treating HIE in the subacute stages (24 h).

12.
Microb Biotechnol ; 12(6): 1226-1236, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31131547

RESUMO

Pichia pastoris KM71H (MutS ) is an efficient producer of hard-to-express proteins such as the membrane protein P-glycoprotein (Pgp), an ATP-powered efflux pump which is expressed properly, but at very low concentration, using the conventional induction strategy. Evaluation of different induction strategies indicated that it was possible to increase Pgp expression by inducing the culture with 20% media containing 2.5% methanol. By quantifying methanol, formaldehyde, hydrogen peroxide and formate, and by measuring alcohol oxidase, catalase, formaldehyde dehydrogenase, formate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenases, it was possible to correlate Pgp expression to the induction strategy. Inducing the culture by adding methanol with fresh media was associated with decreases in formaldehyde and hydrogen peroxide, and increases in formaldehyde dehydrogenase, formate dehydrogenase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenases. At these conditions, Pgp expression was 1400-fold higher, an indication that Pgp expression is affected by increases in formaldehyde and hydrogen peroxide. It is possible that Pgp is responsible for this behaviour, since the increased metabolite concentrations and decreased enzymatic activities were not observed when parental Pichia was subjected to the same growth conditions. This report adds information on methanol metabolism during expression of Pgp from P. pastoris MutS strain and suggests an expression procedure for hard-to-express proteins from P. pastoris.

13.
World J Gastroenterol ; 25(17): 2099-2109, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31114136

RESUMO

BACKGROUND: The methylated septin 9 (mSEPT9) assay was the first blood-based test approved by the United States Food and Drug Administration as a colorectal screening test. However, the diagnostic and prognostic role of preoperative mSEPT9 for colorectal cancer (CRC) in Chinese patients is still unknown. AIM: To improve the understanding of diagnostic and prognostic factors, serum mSEPT9 was detected in Chinese CRC patients. METHODS: A retrospective analysis of 354 cases, of which 300 had CRC and 54 were normal, was performed in China. Patients' characteristics, treatments, and laboratory data, including age, the date of surgery, Union for International Cancer Control (UICC) stages, distant metastasis (M), and so on, were collected. Methylation levels of SEPT9 were quantified by quantitative, methylation-specific polymerase chain reaction before surgery. In addition, the effects of mSEPT9 on the occurrence and prognosis of 330 CRC cases from The Cancer Genome Atlas (TCGA) database were evaluated using bioinformatics analyses. Potential prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier univariate analysis. RESULTS: In Chinese CRC patients, positive mSEPT9 was strongly associated with advanced UICC stages, deeper invasion by the primary tumor, and more distant metastasis. Methylation levels of SEPT9 were stage-dependent and showed a stepwise increase in UICC stages (I-IV), primary tumor categories (T1-T4), regional node categories (N0-N2), and distant metastasis categories (M0-M1). The patients with positive mSEPT9 showed a tendency toward lower PFS. After analyzing TCGA clinical data, the high mSEPT9 group was found to be obviously correlated only with more distant metastasis. The patients with high mSEPT9 levels showed a tendency toward lower OS. Besides, nine meaningful mSEPT9 sites were found to provide guidance for the follow-up studies. CONCLUSION: MSEPT9 analysis may add valuable information to current tumor staging. Serum mSEPT9 in Chinese CRC patients appears to offer promising novel prognostic markers and might be considered for monitoring CRC recurrence.

14.
Medicine (Baltimore) ; 98(16): e15300, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008980

RESUMO

BACKGROUND: Previous clinical studies have reported that furosemide can be used to treat liver cirrhosis (LC) effectively. However, no study systematically explored this issue. This systematic review aims to investigate the efficacy and safety of furosemide for treatment of LC. METHODS: This study will be conducted through searching the following literature sources from their inception to February 28, 2019 without any language limitations: PUBMED, EMBASE, PsycINFO, Web of Science, Scopus, OpenGrey, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. In addition, reference lists of relevant reviews and websites of clinical trial registry will also be searched. Only randomized controlled trials of furosemide for treatment of LC will be included in this study. Two reviewers will independently select studies, collect data, and determine risk of bias. RevMan 5.3 software will be used to pool the data and to conduct meta-analysis if sufficient studies will be included with acceptable heterogeneity. RESULTS: This study will investigate the efficacy and safety of furosemide for LC by the assessment of primary and secondary outcomes. The primary outcome includes mortality rate. The secondary outcomes consist of response rate, overall survival, body weight, urinary volume, quality of life, as measured by any relevant scales, and adverse events. CONCLUSION: The results of this study may provide summarized evidence of furosemide for the treatment of LC. ETHICS AND DISSEMINATION: No individual patient data will be used in this study, thus no ethics approval is needed. The findings of this study will be published in peer-reviewed journals.


Assuntos
Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Diuréticos/efeitos adversos , Furosemida/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Sci Total Environ ; 668: 979-987, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31018476

RESUMO

The giant panda (Ailuropoda melanoleuca) is one of the most endangered animals in the world and is recognized worldwide as a symbol for conservation. The Qinling subspecies of giant panda (Ailuropoda melanoleuca qinlingensis) is highly endangered; fewer than 350 individuals still inhabit the Qinling Mountains. Last year, China announced the establishment of the first Giant Panda National Park (GPNP) with a goal of restoring and connecting fragmented habitats; the proposal ignored the environmental pollution caused by economic development in panda habitats. The spatial distribution of heavy metals (Cd, Pb, Hg, Cu, Zn, Mn, Cr, Ni and As) was analyzed in giant panda feces, soil, bamboo, and water in four of GPNP's functional areas at different altitudes and latitudes. Heavy metal pollution decreased with anthropogenic influences, from outside the park through the buffer and into the core area. Cu, Mn, Ni and Zn accumulated from natural sources; As, Hg and Cr were associated with fuel combustion; and Pb and Cd were associated with traffic and agriculture sources. The presence of heavy metals at high altitudes and latitudes in the proposed GPNP is due to emissions from Xi'an and other upwind industrial cities. We conclude that reducing emissions and heavy metal input should be included in the design of the GPNP. Policy interventions should consider functional zones planning, wind direction, reducing mining, and the abandonment of existing roads and farmland within the GPNP to reduce other direct human impacts on the Qinling panda.


Assuntos
Conservação dos Recursos Naturais , Metais Pesados/análise , Poluentes do Solo/análise , Ursidae , Animais , China , Monitoramento Ambiental , Poluição Ambiental , Fezes/química , Mineração , Análise Multivariada , Parques Recreativos
16.
Environ Res ; 173: 189-198, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30921577

RESUMO

Bisphenol S (BPS), a substitute of bisphenol A (BPA), is widely used for manufacturing different polymers. Due to its wide range of applications, BPS has been frequently detected in the foodstuffs, environment and human blood and excreta. In this study, we examined the effects of the perinatal exposure to BPS on obesity development using 1H NMR based on metabolomics strategy combined with gene expression analysis in male mouse offspring at a dosage of 100 ng/g bw/day. We found that perinatal exposure to BPS significantly increased the body weight, the weights of liver and epididymal white adipose tissue (epiWAT), serum alanine aminotransferase (ALT) activity, and the contents of triglyceride (TG) and cholesterol (T-Cho) in the liver. Histopathological analysis showed that lipids were accumulated significantly in liver tissues and epiWAT with BPS exposure. Furthermore, expressions of genes involved in the inflammatory pathways were significantly increased in liver tissues and epiWAT. Meanwhile, serum metabolomics study showed significant changes in the contents of metabolites associated with lipid and glucose metabolism. Correspondingly, the relative expression levels of genes involved in lipid and glucose metabolism were significantly changed in the liver tissue and epiWAT of male mouse offspring. In conclusion, these results showed that perinatal exposure to BPS may increase the risk of obesity by interfering with lipid and glucose metabolism in male mouse offspring. The potential health risks of BPS in the human required further detailed studies evaluating.

17.
Angew Chem Int Ed Engl ; 58(19): 6235-6238, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-30884058

RESUMO

HemN is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, an intermediate in heme biosynthesis. HemN binds two SAM molecules in the active site, but how these two SAMs are utilized for the sequential decarboxylation of the two propionate groups of coproporphyrinogen III remains largely elusive. Provided here is evidence showing that in HemN catalysis a SAM serves as a hydrogen relay which mediates a radical-based hydrogen transfer from the propionate to the 5'-deoxyadenosyl (dAdo) radical generated from another SAM in the active site. Also observed was an unexpected shunt product resulting from trapping of the SAM-based methylene radical by the vinyl moiety of the mono-decarboxylated intermediate, harderoporphyrinogen. These results suggest a major revision of the HemN mechanism and reveal a new paradigm of the radical-mediated hydrogen transfer in radical SAM enzymology.

18.
Biol Reprod ; 100(6): 1581-1596, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30915454

RESUMO

The corpus luteum (CL) is essential for maintenance of pregnancy in all mammals and luteal rescue, which occurs around day 16-19 in the cow, is necessary to maintain luteal progesterone production. Transcriptomic and proteomic profiling were performed to compare the day 17 bovine CL of the estrous cycle and pregnancy. Among mRNA and proteins measured, 140 differentially abundant mRNA and 24 differentially abundant proteins were identified. Pathway analysis was performed using four programs. Modulated pathways included T cell receptor signaling, vascular stability, cytokine signaling, and extracellular matrix remodeling. Two mRNA that were less in pregnancy were regulated by prostaglandin F2A in culture, while two mRNA that were greater in pregnancy were regulated by interferon tau. To identify mRNA that could be critical regulators of luteal fate, the mRNA that were differentially abundant during early pregnancy were compared to mRNA that were differentially abundant during luteal regression. Eight mRNA were common to both datasets, including mRNA related to regulation of steroidogenesis and gene transcription. A subset of differentially abundant mRNA and proteins, including those associated with extracellular matrix functions, were predicted targets of differentially abundant microRNA (miRNA). Integration of miRNA and protein data, using miRPath, revealed pathways such as extracellular matrix-receptor interactions, abundance of glutathione, and cellular metabolism and energy balance. Overall, this study has provided a comprehensive profile of molecular changes in the corpus luteum during maternal recognition of pregnancy and has indicated that some of these functions may be miRNA-regulated.

19.
J Cell Physiol ; 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30767206

RESUMO

OBJECTIVE: To study the role and mechanism of microRNA 19b (miR-19b) in hypoxia/reoxygenation (H/R)-induced injury by targeting PTEN. METHODS: PC12 and BV2 cells induced by H/R were treated with miR-19b mimics/inhibitors or small interfering PTEN (si-PTEN), respectively. Lactate dehydrogenase (LDH) level, malondialdehyde (MDA), and superoxide dismutase (SOD) content was detected. Besides, cell viability and apoptosis were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Hoechst33342 staining, and flow cytometry, whereas mitochondrial membrane potential (MMP) tested by JC-1 assay, and reactive oxygen species (ROS) evaluated by the dichloro-dihydro-fluorescein diacetate assay. The ischemia/reperfusion (I/R) rats model was used to investigate the effects of miR-19b in vivo test. The infarct area and apoptosis rates in brain tissues were detected by 2,3,5-triphenyltetrazolium chloride and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining, respectively. miR-19b and PTEN/PI3K/Akt pathway-related proteins were detected by quantitative reverse-transcription polymerase chain reaction and western blot analysis. RESULTS: miR-19b mimics could reduce LDH, MDA, and ROS levels and decline cell apoptosis, but enhance the viability, MMP, and SOD activity with decreased PTEN and cleaved caspase, as well as increased p-Akt/Akt and Bcl-2/Bax ratios in H/R-induced PC12 and BV2 cells. However, miR-19b inhibitors led to completely opposite results to aggravate H/R-induced cell injury. Meanwhile, si-PTEN could reverse the effect of miR-19b inhibitors on H/R-induced injury. Moreover, treatment with miR-19b agomir after I/R in vivo sufficiently decreased infarct area and reduced apoptosis rates by targeting PTEN through the regulation of the PI3K/Akt pathway. CONCLUSION: miR-19b could inhibit oxidative stress, enhance cell MMP, promote cell survival, and inhibit cell apoptosis by targeting PTEN via the regulation of the PI3K/Akt pathway, thus playing the neuronal protective effects.

20.
Sci Rep ; 9(1): 2202, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30778089

RESUMO

Parasitoids are insects (usually wasps or flies) that lay eggs within or on other insects (their hosts). Host-feeding parasitoids lay eggs to parasitize the host and feed directly on the host for nourishment. Temperature is the most critical factor affecting insect behavioral responses. Few studies have focused on the impacts of variable temperatures across different life stages on the behaviors of host-feeding parasitoids. This study investigated the effects of temperature experienced during the preadult and adult stages on the life history traits and life table parameters of females of a host-feeding parasitoid, Eretmocerus hayati. Our results show that the temperatures experienced during the preadult and adult stages significantly change life history traits (immature development, adult longevity, host feeding and fecundity). Increasing the preadult temperature resulted in shorter development times for immature stages of the parasitoid, and decreasing the temperature during the adult stage increased reproduction and longevity. Most importantly, we found that host-feeding events changed with temperature rather than life stage. The daily host-feeding ability of the parasitoid increased with increasing temperature at all temperatures except the stress temperature (34 °C). Furthermore, switching temperatures at the immature stage and adult stage can increase the values of life table parameters, with the highest intrinsic rate of increase (r) occurring in the 30/26 °C treatment. This study provides new insight into the mass rearing of parasitic natural enemies.

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