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1.
Sci Total Environ ; 792: 148363, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34465051

RESUMO

The alpine meadow in the Qinghai-Tibet Plateau has been seriously degraded due to human activities and climate change in recent decades. Understanding the changes of the soil microbial community in response to the degradation process helps reveal the mechanism underlying the degradation process of alpine meadows. We surveyed and analyzed changes of the vegetation, soil physicochemical properties, and soil microbial community in three degradation levels, namely, non-degradation (ND), moderate degradation (MD), and severe degradation (SD), of the alpine meadows in the northeastern Qinghai-Tibet Plateau. We found that as the level of degradation increased, plant cover, plant density (PD), above-ground biomass (AGB), plant Shannon-Wiener index (PS), soil water content (SWC), soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), available nitrogen (AN), available phosphorus (AP), and available potassium (AK) decreased significantly, while the soil pH increased from 7.20 to 8.57. Alpine meadow degradation significantly changed the composition of soil bacterial and fungal communities but had no significant impact on the diversity of the microbial communities. Functional predictions indicated that meadow degradation increased the relative abundances of aerobic_chemoheterotrophy, undefined_saprotroph, and plant_pathogen, likely increasing the risk of plant diseases. Redundancy analysis revealed that in ND, the soil microbial community was mainly regulated by PS, PH, PD, SWC, and soil pH. In MD, the soil microbial community was regulated by the soil's available nutrients and SOC. In SD, the soil microbial community was not only regulated by the soil's available nutrients but also influenced by plant characteristics. These results indicate that during alpine meadow degradation, while the changes in the plants and soil environmental factors both affect the composition of the soil microbial community, the influence of soil factors is greater. The soil's available nutrients are the main driving factors regulating the change in the soil microbial community's composition alongside degradation levels.


Assuntos
Microbiota , Solo , Carbono/análise , Pradaria , Humanos , Nutrientes , Microbiologia do Solo , Tibet
2.
Nat Commun ; 12(1): 4408, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344888

RESUMO

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS.


Assuntos
Testes para Triagem do Soro Materno/métodos , Placenta Acreta/diagnóstico , Trofoblastos/patologia , Adulto , Biomarcadores/sangue , Agregação Celular , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Dispositivos Lab-On-A-Chip , Testes para Triagem do Soro Materno/instrumentação , Pessoa de Meia-Idade , Nanoestruturas , Placenta Acreta/sangue , Placenta Prévia/sangue , Placenta Prévia/diagnóstico , Gravidez , Curva ROC , Reprodutibilidade dos Testes
3.
J Microbiol Biotechnol ; 31(9): 1218-1230, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34261854

RESUMO

Cold-adapted plant growth-promoting bacteria (PGPB) with multiple functions are an important resource for microbial fertilizers with low-temperature application. In this study, culturable cold-adapted PGPB strains with nitrogen fixation and phosphorus solubilization abilities were isolated. They were screened from root and rhizosphere of four dominant grass species in nondegraded alpine grasslands of the Qilian Mountains, China. Their other growth-promoting characteristics, including secretion of indole-3-acetic acid (IAA), production of siderophores and ACC deaminase, and antifungal activity, were further studied by qualitative and quantitative methods. In addition, whether the PGPB strains could still exert plant growth-promoting activity at 4°C was verified. The results showed that 67 isolates could maintain one or more growth-promoting traits at 4°C, and these isolates were defined as cold-adapted PGPB. They were divided into 8 genera by 16S rRNA gene sequencing and phylogenetic analysis, of which Pseudomonas (64.2%) and Serratia (13.4%) were the common dominant genera, and a few specific genera varied among the plant species. A test-tube culture showed that inoculation of Elymus nutans seedlings with cold-adapted PGPB possessing different functional characteristics had a significant growth-promoting effect under controlled low-temperature conditions, including the development of the roots and aboveground parts. Pearson correlation analysis revealed that different growth-promoting characteristics made different contributions to the development of the roots and aboveground parts. These cold-adapted PGPB can be used as excellent strain resources suitable for the near-natural restoration of degraded alpine grasslands or agriculture stock production in cold areas.

4.
BMC Fam Pract ; 22(1): 23, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-33453725

RESUMO

BACKGROUND: Domestic migration poses a challenge for China as migrants have little access to preventive healthcare services and are vulnerable to certain risks and diseases. This research sought to unveil and explore the determinant factors associated with health education utilization as a key aspect in basic public health services for migrants in Beijing, China. METHODS: A sample of 863 inter-provincial migrants, 18 years old and above, was selected by three-stage stratified cluster sampling method in urban-rural fringe areas of Beijing during 2016 to 2017. Face-to-face structured interviews were conducted in the questionnaire survey. The effects of the explanatory variables on health education utilization from predisposing, enabling, health behaviors and need variables were used to demonstrate by Anderson health service utilization model. RESULTS: The study revealed that 61.6% migrants desired to receive health education, while only 53.8% of them received in the past year. There were differences in the utilization and needs of health education among the migrants in different ages and genders. Many migrants desired to gain access to various types of health education information from the internet. Chi-square independence test lists such major determinant factors in migrants whole health education as age, "Hukou" registration system, marital status, education level, long-term residence plan in Beijing, one or more children in Beijing, employment status, housing source, average daily working time, exercises, health knowledge, smoking, self-rated health. The binary logistic regression indicates that the migrants with younger age, high education level, one or more children in Beijing, exercises and good self-rated health were more likely to receive whole health education. The results also show that average daily working time of enabling variables and exercise of health behavior variables were the strong and consistent determinants of three types of health education utilization, including communicable, non-communicable and occupational diseases. CONCLUSION: Gaps exist between the needs and utilization in health education and more attention should be given to the migrants with heavy workload and low education level. Feasible policies and measures, such as multiple health information channels, should be vigorously implemented to ensure equitable and easy access to health education for migrants.


Assuntos
Migrantes , Pequim , China , Estudos Transversais , Utilização de Instalações e Serviços , Feminino , Educação em Saúde , Humanos , Masculino , População Rural
5.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 560-564, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879107

RESUMO

OBJECTIVES: To analyze the clinical characteristics of fecal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid-positive in patients with coronavirus dasease 2019 (COVID-19) and to provide a scientific basis for the prevention and control of this disease. METHODS: The clinical data of 16 patients with fecal SARS-CoV-2 nucleic acid positive, who hospitalized in the North Branch of the First Hospital of Changsha (Changsha Public Health Rescue Center) from January to February 2020, were retrospectively analyzed. Their clinical manifestations, laboratory data and imaging data were summarized. RESULTS: Among the 16 patients, there were 9 males (56.25%) and 7 females (43.75%), the ratio of males to females was 1∶1.29. The age of onset was (43.3±14.6) years. There were 15 patients with contact history of Wuhan, 1 patient with contact history of local patient.Twelve patients were common type (75%), and 4 patients were severe type (25%). Clinical symptoms included fever in 14 patients (87.5%), cough in 12 patients (75%), shortness of breath in 5 patients (31.25%), pharyngalgia in 10 patients (62.5%), fatigue in 7 patients (43.75%), and diarrhea in 4 patients (25%). There were 14 patients (87.5%) with normal or decreased white blood cell count, 11 patients (68.75%) with decreased lymphocyte count, 15 patients (93.75%) with increased erythrocyte sedimentation rate, 13 patients (81.25%) with increased hypersensitivity C-reactive protein, 5 patients (31.25%) with increased procalcitonin, and 8 patients (50%) with increased serum ferritin in peripheral blood, and stool routine was basically normal. Compared with the common type, there was significant difference in the white blood cell and lymphocyte counts in the severe type (P<0.01); the infection indicators, such as hypersensitivity C-reactive protein and serum ferritin, were significantly increased, with significant difference (all P<0.01); but the procalcitonin and erythrocyte sedimentation rate was not significantly different (both P>0.05). Chest CT mainly showed patchy shadows and interstitial changes. According to imaging examination, 4 patients (25%) showed unilateral pneumonia and 12 patients (75%) showed bilateral pneumonia. CONCLUSIONS: The patients have the clinical symptoms of COVID-19, but gastrointestinal symptoms (such as diarrhea) are more common, and the changes of white blood cell count, lymphocyte count, hypersensitivity C-reactive protein, ferritin are more obvious in severe patients.The positivity of fecal nucleic acid suggests the possibility of digestive tract transmission of SARS-CoV-2, and fecal nucleic acid testing can be used as a routine testing method in clinical practice.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Adulto , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/análise , COVID-19 , China , Infecções por Coronavirus/fisiopatologia , Diarreia/virologia , Fezes/virologia , Feminino , Ferritinas/análise , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos , SARS-CoV-2
6.
Environ Int ; 139: 105672, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32248022

RESUMO

There are currently increasingly concerns over DNA damage related to free radicals due to their vital roles in human health, especially high-performance detection method. Herein, we report an ultra- sensitive monitoring of DNA damage associated with free radicals exposure using interdigitated electrode (IDE) array for the first time. The proposed IDE array was equipped with DNA-wrapped carbon nanotube-based bridges, which utilized the DNA damage mechanism due to the free radicals' attack and the efficient electrical detection nature of the interdigitated electrode. Experiments have been performed, and the results showed the device's capability for detecting DNA damage induced by multiple free radicals generated from different sources, including the Fenton reaction, UV radiation and cigarette smoke, showing the promising ability for DNA damage detection. In addition, the carbon nanotubes bridge-based interdigitated electrode sensor enabled different levels of sensing of DNA damage with great sensitivity and a wide detection range. It was illustrated that the ultrasensitive detection of free radicals generated from ultraviolet radiation (15 min - 125 min), cigarette smoke tar (1 µg/mL to 10 µg/mL) and Fenton reaction under different concentration of H2O2 (2.5 pM - 100 pM), have been detected successfully. Typically, the IDE array supports further performance improvement for the electrochemical detection in an ultrasensitive and high throughput route.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Dano ao DNA , Eletrodos , Humanos , Peróxido de Hidrogênio , Nanotubos de Carbono/toxicidade , Raios Ultravioleta
7.
J Cell Mol Med ; 24(11): 6362-6372, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319715

RESUMO

Glioblastoma (GBM) belongs to the high-grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non-coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435-2 Host Gene (MIR4435-2HG) in GBM. Data from GEPIA database showed that MIR4435-2HG was up-regulated in GBM tissues and high expression of MIR4435-2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up-regulation of MIR4435-2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435-2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435-2HG overexpression driven GBM progression. Furthermore, MIR44435-2HG was found to sponge miR-1224-5p and suppress miR-1224-5p expression; overexpression of miR-1224-5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435-2HG overexpression. In a subsequent study, miR-1224-5p was found to target transforming growth factor-beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR-1224-5p exerted tumour-suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper-proliferation and invasion of GBM cells with MIR4435-2HG overexpression. Clinically, the down-regulation of miR-1224-5p and up-regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435-2HG in GBM and underlies the key function of MIR4435-2HG-driven GBM progression via targeting miR-1224-5p/TGFBR2 axis.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Transdução de Sinais , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Regulação para Cima/genética
8.
Cell Rep ; 31(4): 107564, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32348766

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that exhibits two alternative life cycles: latency and lytic reactivation. During lytic reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that adenosine deaminase acting on RNA 1 (ADAR1) is required for optimal KSHV lytic reactivation from latency. Knockdown of ADAR1 in KSHV latently infected cells inhibits viral gene transcription and viral replication during KSHV lytic reactivation. ADAR1 deficiency also significantly increases type I interferon production during KSHV reactivation. This increased interferon response is dependent on activation of the RIG-I-like receptor (RLR) pathway. Depletion of ADAR1 together with either RIG-I, MDA5, or MAVS reverses the increased IFNß production and rescues KSHV lytic replication. These data suggest that ADAR1 serves as a proviral factor for KSHV lytic reactivation and facilitates DNA virus reactivation by dampening the RLR pathway-mediated innate immune response.


Assuntos
Adenosina Desaminase/metabolismo , Proteína DEAD-box 58/metabolismo , Herpesvirus Humano 8/fisiologia , Proteínas de Ligação a RNA/metabolismo , Receptores Imunológicos/metabolismo , Técnicas de Inativação de Genes , Células HEK293 , Herpesvirus Humano 8/metabolismo , Humanos , Interferon beta/biossíntese , Transdução de Sinais , Ativação Viral , Latência Viral
9.
BMC Res Notes ; 13(1): 28, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931876

RESUMO

OBJECTIVE: This report is a side product of experiments aimed at identifying serum for culturing obligate intracellular bacteria Chlamydia trachomatis and C. muridarum in mouse fibroblast L929 cells. RESULTS: Of five commercial serum samples tested, two showed optimal efficiencies at supporting growth of the human pathogen Chlamydia trachomatis as control fetal bovine serum, whereas two showed modest ~ 40% inhibitions in progeny production, and the remaining one showed a 20% inhibition. Three of the six sera poorly supported growth of the murine pathogen Chlamydia muridarum, resulting in 73-90% reduction in progeny formation. Most significantly, the one with the strongest (90%) C. muridarum inhibition activity showed optimal C. trachomatis-supporting efficiency. These findings indicate that in laboratories that study multiple Chlamydia species, serum samples should be prescreened on a species basis. Considering Chlamydial biology and epidemiology, it may even be necessary to perform serum tests on a serovar- or strain-basis for studying some animal chlamydiae.


Assuntos
Chlamydia muridarum/crescimento & desenvolvimento , Chlamydia trachomatis/crescimento & desenvolvimento , Animais , Linhagem Celular , Chlamydia muridarum/fisiologia , Chlamydia trachomatis/fisiologia , Meios de Cultura , Camundongos , Soro/química
10.
Environ Pollut ; 259: 113841, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31883477

RESUMO

Nicotine (Nic) exposed to the environment which comes from tobacco products is the main addictive agent and specific classes of hazardous compound that merit concern. In this study, we have established a fast and reliable method to achieve specific detection of Nic in natural nicotiana tabacum within 30 s through a miniaturized platform based on screen printed gold electrode (SPE). A simple electrochemical pretreatment mean was employed on gold surface that led to the exposure of Au (111) facet and a convenient sample pretreatment method was adopted to realize the extraction of Nic in tobacco. The present electrochemical sensor exhibits an ample range of sensing from 10 µg/g to 200 µg/g, which is able to compliance with tobacco industry testing standards of actual samples. Over 60 sampling points from different origins in China or other countries were performed with direct analysis using this method and satisfactory results have been obtained. The proposed approach was demonstrated to be a very promising platform for significantly improving analytical efficiency in laboratories as well as for monitoring the source reduction control of Nic in the environment.


Assuntos
Técnicas de Química Analítica/métodos , Nicotina , Tabaco , China , Eletrodos , Nicotina/análise , Tabaco/química
11.
J Hazard Mater ; 389: 121834, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-31843407

RESUMO

Environmental problems caused by the large-scale use of chemical pesticides are becoming more and more serious, and the removal of chemical pesticides from the ecological environment by microbial degradation has attracted wide attention. In this study, using enrichment screening with seven chemical pesticides as the sole carbon source, a mixed microbial culture (PCS-1) was obtained from the continuous cropping of strawberry fields. The microbial community composition, degradation ability, and detoxification effect of PCS-1 was determined for the seven pesticides. Inoculation with PCS-1 showed significant degradation of and tolerance to the seven pesticides. Microbial community composition analysis indicated that Pseudomonas, Enterobacter, Aspergillus, and Rhodotorula were the dominant genera for the degradation of the seven pesticides by PCS-1. The concentration of the seven pesticides was 10 mg L-1 in hydroponic and soil culture experiments. The fresh weight, plant height, and root length of PCS-1-inoculated alfalfa (Medicago sativa) significantly increased compared with those of non-PCS-1-inoculated M. sativa. PCS-1 not only effectively degraded the residual content of the seven pesticides in water and soil but also reduced the pesticide residues in the roots, stems, and leaves of M. sativa. This study shows that PCS-1 may be important in environmental remediation involving the seven pesticides.


Assuntos
Poluentes Ambientais/análise , Medicago sativa/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Praguicidas/análise , Microbiologia do Solo , Poluentes do Solo/análise , Aspergillus/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Biodegradação Ambiental , Enterobacter/efeitos dos fármacos , Enterobacter/crescimento & desenvolvimento , Poluentes Ambientais/toxicidade , Medicago sativa/crescimento & desenvolvimento , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Pseudomonas/efeitos dos fármacos , Pseudomonas/crescimento & desenvolvimento , Rhodotorula/efeitos dos fármacos , Rhodotorula/crescimento & desenvolvimento , Poluentes do Solo/toxicidade
12.
J Cancer ; 10(24): 6095-6104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762819

RESUMO

BACKGROUND: Circulating tumor cell (CTC)-based patient-derived cells are ideal models for investigating the molecular basis of cancer. However, the rarity and heterogeneity of CTCs as well as the difficulties of primary culture limit their practical application. Establishing efficient in vitro culture methods and functionally characterizing CTCs is essential for cancer studies. To this end, we developed an experimental protocol for the isolation, expansion, and identification of breast cancer CTCs. METHODS: The CTC-3 cell line was established from peripheral blood cells of a breast cancer patient. A karyotype analysis was performed. The molecular profile was assessed by flow cytometry, quantitative real-time PCR, and western blot. The characteristics of tumors formed by CTC-3 cells were evaluated by cell growth and tumor sphere formation assays and in a mouse xenograft model. The tumors were analyzed by immunohistochemistry, immunofluorescence analysis, and hematoxylin and eosin staining. RESULTS: The CTC-3 cell line showed more aggressive growth both in vitro and in vivo than the widely used MCF-7 breast cancer cell line. CTC-3 cells were also more resistant to chemotherapeutic agents, and gene profiling indicated higher expression levels of the epithelial-to-mesenchymal transition and stemness markers as compared to MCF-7 cells. CONCLUSIONS: CTC-3 cells are a better model for investigating the malignant behavior of breast cancer than existing cell lines.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31661944

RESUMO

A growing body of research has shown that people's attitudes toward food safety is affected by their availability and accessibility to food risk information. In the digital era, the Internet has become the most important channel for information acquisition. However, empirical evidence related to the impact of Internet use on people's attitudes towards food safety is inadequate. In this study, by employing the Chinese Social Survey for 2013 and 2015, we have investigated the current situation of food safety perceptions and evaluations among Chinese residents and the association between Internet use and individuals' food safety evaluations. Empirical results indicate that there is a significant negative correlation between Internet use and people's food safety evaluation in China. Furthermore, heterogeneity analysis shows that Internet use has a stronger negative correlation with food safety evaluation for those lacking rational judgment regarding Internet information. Specifically, the negative correlation between Internet use and food safety evaluations is more obvious among rural residents, young people, and less educated residents. Finally, propensity score matching (PSM) is applied to conduct a robustness check. This paper provides new evidence for studies on the relationship between Internet use and an individuals' food safety cognition, as well as additional policy enlightenment for food safety risk management in the digital age.


Assuntos
Atitude , Inocuidade dos Alimentos , Internet/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Fatores Socioeconômicos
14.
Nutr Metab (Lond) ; 16: 37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31160916

RESUMO

Background: Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy. Methods: A total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS). Results: The distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively. Conclusions: This study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy.

15.
Life Sci ; 231: 116576, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31211998

RESUMO

AIMS: Studies suggest that cardiovascular function in offspring can be epigenetically programmed by environmental changes during pregnancy. CaV1.2 channel plays a major role in the regulation of the vascular tone. This study investigated the effects and underlying mechanisms of exercise during pregnancy on CaV1.2 channel functional remodeling in hypertensive offspring. MAIN METHODS: Exercise groups were subjected to swimming at the first day of pregnancy and on a regular schedule thereafter for 3 weeks. Their offspring (6-month-old, male) were tested for baseline blood pressure, cardiovascular response, and vascular tone of the mesenteric artery. Mesenteric artery smooth muscle cells were taken to study the whole-cell current of the CaV1.2 channel. Western blotting, RT-PCR and DNA bisulfite sequencing PCR were performed to study the protein, mRNA expression and DNA methylation of the CaV1.2 channel α1C subunit. KEY FINDINGS: Exercise during pregnancy reduced the pressor response to norepinephrine and Bay K8644, and the depressor response to nifedipine in offspring of hypertensive rats. The level of the CaV1.2 channel in norepinephrine-induced vasoconstrictions decreased, and the whole-cell current of the CaV1.2 channel declined in the SHR-EX group. Further studies found that exercise during pregnancy reduced the protein and mRNA expression of the CaV1.2 channel α1C subunit and upregulated DNA methylation of the Cacna1c gene promoter region in the hypertensive offspring. SIGNIFICANCE: These data suggest that exercise during pregnancy improves vascular functional remodeling in offspring of hypertensive rats, downregulating the CaV1.2 channel function and protein expression, a change that is most likely caused by DNA methylation.


Assuntos
Canais de Cálcio Tipo L/fisiologia , Hipertensão/fisiopatologia , Condicionamento Físico Animal/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo , Epigênese Genética/genética , Repressão Epigenética , Feminino , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Gravidez , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Regulação para Cima , Vasoconstrição/efeitos dos fármacos
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(5): 485-490, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31104668

RESUMO

OBJECTIVE: To study the expression of Shh and Wnt5a genes in the limb buds of NIPBL+/- fetal rats and the association of these two genes with Cornelia de Lange syndrome (CdLS). METHODS: A total of 72 NIPBL+/- fetal rats were divided into an experimental group and a control group, with 36 rats in each group. The limb buds were collected from 12 fetal rats each on embryonic days 10, 11 and 12 (E10, E11 and E12) respectively. Real-time PCR and Western blot were used to measure the mRNA and protein expression of Shh and Wnt5a. RESULTS: The mRNA and protein expression of Shh and Wnt5a was detected in the limb buds on E10, E11 and E12, and the experimental group had significantly lower expression than the control group (P<0.01). The mRNA and protein expression of Shh and Wnt5a in limb buds was at a low level on E10, followed by an increase on E11 and a reduction on E12, and the expression on E12 was still lower than that on E10 (P<0.01). CONCLUSIONS: The mRNA and protein expression of Shh and Wnt5a are consistent. The pathogenesis of CdLS may be associated with the low mRNA and protein expression of Shh and Wnt5a inhibited by the low expression of NIPBL gene.


Assuntos
Síndrome de Cornélia de Lange , Animais , Proteínas Hedgehog , Mutação , Fenótipo , Proteínas , RNA Mensageiro , Ratos , Proteína Wnt-5a
17.
PLoS One ; 14(3): e0212874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30822328

RESUMO

Chlamydia is a common pathogen that can causes serious complications in the reproductive system and eyes. Lack of vaccine and other effective prophylactic measures coupled with the largely asymptomatic nature and unrare clinical treatment failure calls for development of new antichlamydials, particularly selective antichlamydials without adverse effects on humans and the beneficial microbiota. We previously reported that benzal-N-acylhydrazones (BAH) can inhibit chlamydiae without detectable adverse effects on host cells and beneficial lactobacilli that dominate the human vaginal microbiota among reproductive-age women. However, the antichlamydial mechanism of BAH is not known. Whereas 4 single nucleotide polymorphisms (i.e., SNP1-4) were identified in a rare Chlamydia variant with a low level of BAH resistance, termed MCR, previous studies failed to establish a causal effect of any particular SNP(s). In the present work, we performed recombination to segregate the four SNPs. Susceptibility tests indicate that the R51G GrgA allele is both necessary and sufficient for the low level of BAH resistance. Thus, the Chlamydia-specific transcription factor GrgA either is a direct target of BAH or regulates BAH susceptibility. We further confirm an extremely low rate of BAH resistance in Chlamydia. Our findings warrant exploration of GrgA as a therapeutic and prophylactic target for chlamydial infections.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Chlamydia muridarum/genética , Farmacorresistência Bacteriana/genética , Fatores de Transcrição/genética , Animais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/antagonistas & inibidores , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/uso terapêutico , Linhagem Celular , Infecções por Chlamydia/tratamento farmacológico , Infecções por Chlamydia/microbiologia , Chlamydia muridarum/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Hidrazonas/farmacologia , Hidrazonas/uso terapêutico , Camundongos , Testes de Sensibilidade Microbiana , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/antagonistas & inibidores
18.
Eur J Pharmacol ; 842: 177-188, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30391348

RESUMO

The pineal hormone melatonin is a neuroendocrine hormone with high membrane permeability that is involved in regulation of circadian rhythm of several biological functions. Large-conductance Ca2+-activated K+ (BKCa) channels are abundantly expressed in vascular smooth muscle cells and play an important role in vascular tone regulation. We investigated the mechanisms through which myocyte BKCa channels mediate effects of melatonin on cerebral arteries (CAs). Arterial contractility measurements showed that melatonin alone did not change vascular tone in CAs; however, it induced concentration-dependent vasodilation of phenylephrine-induced contraction in CAs. In the presence of the potent endothelial oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester, melatonin-elicited relaxation was significantly inhibited by iberiotoxin (BKCa channel blocker). Melatonin significantly increased BKCa currents but not voltage-gated K+ (KV) currents in whole-cell recordings. Melatonin decreased the amplitude of Ca2+ sparks and spontaneous transient outward currents (STOCs), however, a significant increase in open probability of BKCa channels was observed in both inside-out and cell-attached patch-clamp recordings. This melatonin-induced enhancement of BKCa channel activity was significantly suppressed by luzindole (melatonin MT1/MT2 receptor inhibitor), U73122 (phospholipase C (PLC) inhibitor), and Ro31-8220 (protein kinase C (PKC) inhibitor). Melatonin had no significant effects on sarcoplasmic reticulum release of Ca2+. These findings indicate that melatonin-induced vasorelaxation of CAs is partially attributable to direct (passing through the cell membrane) and indirect (via melatonin MT1/MT2 receptors-PLC-PKC pathway) activation of BKCa channels on CA myocytes.


Assuntos
Artérias Cerebrais/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Melatonina/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Artérias Cerebrais/citologia , Artérias Cerebrais/fisiologia , Relação Dose-Resposta a Droga , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Masculino , Miócitos de Músculo Liso/metabolismo , Peptídeos/farmacologia , Ratos , Ratos Wistar
19.
BMC Genomics ; 19(1): 833, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30463521

RESUMO

BACKGROUND: Chromosomal level reference genomes provide a crucial foundation for genomics research such as genome-wide association studies (GWAS) and whole genome selection. The chromosomal-level sequences of both the European (Pyrus communis) and Chinese (P. bretschneideri) pear genomes have not been published in public databases so far. RESULTS: To anchor the scaffolds of P. bretschneideri 'DangshanSuli' (DS) v1.0 genome into pseudo-chromosomes, two genetic maps (MH and YM maps) were constructed using half sibling populations of Chinese pear crosses, 'Mantianhong' (MTH) × 'Hongxiangsu' (HXS) and 'Yuluxiang' (YLX) × MTH, from 345 and 162 seedlings, respectively, which were prepared for SNP discovery using genotyping-by-sequencing (GBS) technology. The MH and YM maps, each with 17 linkage groups (LGs), were constructed from 2606 and 2489 SNP markers and spanned 1847 and 1668 cM, respectively, with average marker intervals of 0.7. The two maps were further merged with a previously published genetic map (BD) based on the cross 'Bayuehong' (BYH) × 'Dangshansuli' (DS) to build a new integrated MH-YM-BD map. By using 7757 markers located on the integrated MH-YM-BD map, 898 scaffolds (400.57 Mb) of the DS v1.0 assembly were successfully anchored into 17 pseudo-chromosomes, accounting for 78.8% of the assembled genome size. About 88.31% of them (793 scaffolds) were directionally anchored with two or more markers on the pseudo-chromosomes. Furthermore, the errors in each pseudo-chromosome (especially 1, 5, 7 and 11) were manually corrected and pseudo-chromosomes 1, 5 and 7 were extended by adding 19, 12 and 14 scaffolds respectively in the newly constructed DS v1.1 genome. Synteny analyses revealed that the DS v1.1 genome had high collinearity with the apple genome, and the homologous fragments between pseudo-chromosomes were similar to those found in previous studies. Moreover, the red-skin trait of Asian pear was mapped to an identical locus as identified previously. CONCLUSIONS: The accuracy of DS v1.1 genome was improved by using larger mapping populations and merged genetic map. With more than 400 MB anchored to 17 pseudo-chromosomes, the new DS v1.1 genome provides a critical tool that is essential for studies of pear genetics, genomics and molecular breeding.


Assuntos
Mapeamento Cromossômico , Cromossomos de Plantas , Genoma de Planta , Genômica/métodos , Pyrus/genética , Evolução Molecular , Ligação Genética , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único
20.
Nanoscale ; 10(43): 20354-20365, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30376015

RESUMO

Recently, mesoporous silica nanoparticles (MSNs) have become popular nanomaterials in smart delivery systems. Although research progress in the application of MSNs as pesticide carriers has been achieved, multifunctional MSNs endowed with bright luminescent centers facilitating the tracking of MSNs in biological systems and versatile structural properties possessing a high drug loading capacity and regulable release are still highly desirable. In the present work, we reported a fluorophore-free method to endow MSNs with stable fluorescence and a double-shelled hollow structure; they were prepared by a selective-etching strategy and subsequent annealing treatment. The strong and stable luminescence is found to originate from the carbon dots generated from the calcination. Their well-defined morphological structure was confirmed by SEM and TEM imaging. These versatile silica nanoparticles served as a novel delivery system for the pesticide pyraclostrobin with a loading content of 28.5%. The pyraclostrobin-loaded nanoparticles showed an initial burst, followed by subsequent sustained release behavior. The fungicidal activity of pyraclostrobin-loaded silica nanoparticles against the fungus Phomopsis asparagi (Sacc.) as well as their visual observation in the mycelium was explored. Furthermore, the effect of pyraclostrobin-loaded nanoparticles on the morphology and ultrastructure of the mycelium was investigated by SEM and TEM observations. This research seeks to develop a novel nanocarrier platform for the potential application of pesticides in sustainable plant protection.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Praguicidas/química , Dióxido de Silício/química , Ascomicetos/efeitos dos fármacos , Liberação Controlada de Fármacos , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Tamanho da Partícula , Praguicidas/metabolismo , Espectroscopia Fotoeletrônica , Porosidade , Espectrometria de Fluorescência , Estrobilurinas/química , Estrobilurinas/farmacologia
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