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1.
Chemosphere ; 262: 128404, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182127

RESUMO

BACKGROUND: Reduced growth velocity before birth increases the risk of adverse health outcomes in adult life. However, until recently, there has been a lack of studies demonstrating the impact of prenatal PM2.5 exposure on fetal growth velocity. METHODS: The current study was embedded in a previous cohort built between January 1, 2014, and April 30, 2015, in Shanghai First Maternity and Infant Hospital, China, in 6129 eligible singleton pregnancies. The PM2.5 concentration was estimated by an inverse distance weighted method according to the residential addresses of the participants. Repeated fetal biometry measurements, including head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD), were measured through ultrasound between 14 and 41 gestational weeks. A principal component analysis through conditional expectation for sparse longitudinal data was used to estimate the corresponding velocities. RESULTS: A total of 22782 ultrasound measurements were conducted among 6129 participants with a median of 2 and a maximum of 9 measurements. With each 10 µg/m3 increase in cumulative PM2.5 exposure, the velocity of HC, AC FL and BPD decreased by 0.12 mm/week, 0.17 mm/week, 0.02 mm/week and 0.02 mm/week, respectively, on average. The results of the Generalized Functional Concurrent Model showed that the velocity decreased significantly with PM2.5 exposure between 22 and 32 gestational weeks, which might be the potential sensitive exposure window. CONCLUSIONS: There are negative associations between prenatal exposure to PM2.5 and fetal growth velocity, and the late second trimester and early third trimester might be the potential sensitive window.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Materna , Material Particulado/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Adulto , China , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Masculino , Material Particulado/análise , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos
2.
Gene ; 766: 145156, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32949696

RESUMO

Plant Glycogen Synthase Kinase 3 (GSK3)/SHAGGY-like kinase (GSK) proteins play important roles in modulating growth, development, and stress responses in several plant species. However, little is known about the members of the potato GSK (StGSK) family. Here, nine StGSK genes were identified and phylogenetically grouped into four clades. Gene duplication analysis revealed that segmental duplication contributed to the expansion of the StGSK family. Gene structure and motif pattern analyses indicated that similar exon/intron and motif organizations were found in StGSKs from the same clade. Conserved motif and kinase activity analyses indicated that the StGSKs encode active protein kinases, and they were shown to be distributed throughout whole cells. Cis-acting regulatory element analysis revealed the presence of many growth-, hormone-, and stress-responsive elements within the promoter regions of the StGSKs, which is consistent with their expression in different organs, and their altered expression in response to hormone and stress treatments. Association network analysis indicated that various proteins, including two confirmed BES1 family transcription factors, potentially interact with StGSKs. Overexpression of StSK21 provides enhanced sensitivity to salt stress in Arabidopsis thaliana plants. Overall, these results reveal that StGSK proteins are active protein kinases with purported functions in regulating growth, development, and stress responses.


Assuntos
Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas/genética , Família Multigênica/genética , Proteínas de Plantas/genética , Estresse Salino/genética , Solanum tuberosum/genética , Estresse Fisiológico/genética , Arabidopsis/genética , Cromossomos de Plantas/genética , Duplicação Gênica/genética , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla/métodos , Filogenia , Reguladores de Crescimento de Planta/genética , Fatores de Transcrição/genética
3.
J Ethnopharmacol ; 264: 113322, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32871236

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Melastoma consists of approximately 100 species distributed widely in tropical and subtropical countries, and Melastoma species are often used for medicinal purposes, such as treatment for bleeding, diarrhea, diabetes, and gynecological tumors by local people, mostly in Southeast Asian countries. AIM OF THE REVIEW: The present review summarizes the traditional uses, phytochemistry and pharmacology of species belonging to Melastoma to suggest further research strategies and to facilitate the exploitation of the therapeutic potential of Melastoma species for the treatment of human disorders. MATERIALS AND METHODS: Information related to the traditional uses, phytochemistry and pharmacological activities was systematically collected by searching for the word "Melastoma" in electronic databases, including SciFinder, Web of Science, PubMed, and Google Scholar, from Apr. 1968 until Dec. 2019. RESULTS: A systematic literature survey revealed that Melastoma spp. are widely distributed in southern Asia to northern Oceania and the Pacific Islands and are traditionally used to treat bleeding, diarrhea, swelling, and gynecological tumors. Approximately 142 compounds, including flavonoids, tannins, phenylpropanoids, organic acids, terpenoids, and steroids, have been reported from Melastoma spp. Different extracts have been evaluated for their pharmacological activities, including anti-inflammatory, hemostatic, anticoagulant, cytotoxic, antibacterial, antioxidant, hepatoprotective, gastroprotective and hypoglycemic activities. CONCLUSIONS: Melastoma spp. are popularly used in Southeast Asian countries as effective herbs and are rich in flavonoids, tannins and organic acids with valuable medicinal properties. However, additional studies of the chemical constituents and the mechanism-based pharmacological activities of many members of Melastoma are still needed for developing new plant-derived drugs. In addition, studies on the clinical safety and efficacy of Melastoma are also needed.

4.
Environ Int ; 146: 106243, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33161204

RESUMO

BACKGROUND: The prevalence of allergic diseases in children has increased globally. Early-life exposure to inorganic arsenic has been found to be associated with impaired immune function and decreased lung function in children; however, the results are inconsistent. We aimed to evaluate the effect of prenatal and childhood exposure to inorganic arsenic on allergic diseases in children, through a 15-year follow-up birth cohort study, conducted in central Taiwan. METHODS: Children born to women enrolled in the Taiwan Maternal and Infant Cohort Study (TMICS-pilot) from December 2000 to November 2001 were recruited and followed every 2-3 years until the age of 14 years. Urinary specimens were collected in the pregnant women during the 3rd trimester and the followed children. Diagnoses of allergic diseases were based on physician diagnoses using the International Study of Asthma and Allergies in Childhood questionnaire. Urinary arsenic speciation was performed using high-performance liquid chromatography and inductively coupled plasma dynamic reaction cell mass spectrophotometry. RESULTS: Of the 261 children from 358 mother-infant pairs for this study, those with asthma and allergic rhinitis reported a higher prevalence of maternal allergy (49.47%) than did non-allergic children (29.81%). In the fully adjusted model, levels of maternal urine (iAs + MMA + DMA) greater than the median were found to be significantly associated with an increased risk of asthma (OR = 4.28; 95% CI 1.32, 13.85). Levels of urinary (iAs + MMA + DMA) in children higher than the median were associated with an increased risk of allergic rhinitis (OR = 2.26; 95% CI 1.20, 4.26). CONCLUSION: Prenatal and childhood exposure to inorganic arsenic were found to be significantly associated with the occurrence of asthma and allergic rhinitis in children, respectively. Further large cohort follow-up studies are important to validate the association between inorganic arsenic exposure and allergic diseases in children.

5.
Ultrasonics ; 110: 106271, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33166786

RESUMO

Accurate breast mass segmentation of automated breast ultrasound (ABUS) is a great help to breast cancer diagnosis and treatment. However, the lack of clear boundary and significant variation in mass shapes make the automatic segmentation very challenging. In this paper, a novel automatic tumor segmentation method SC-FCN-BLSTM is proposed by incorporating bi-directional long short-term memory (BLSTM) and spatial-channel attention (SC-attention) module into fully convolutional network (FCN). In order to decrease performance degradation caused by ambiguous boundaries and varying tumor sizes, an SC-attention module is designed to integrate both finer-grained spatial information and rich semantic information. Since ABUS is three-dimensional data, utilizing inter-slice context can improve segmentation performance. A BLSTM module with SC-attention is constructed to model the correlation between slices, which employs inter-slice context to assist segmentation for false positive elimination. The proposed method is verified on our private ABUS dataset of 124 patients with 170 volumes, including 3636 2D labeled slices. The Dice similarity coefficient (DSC), Recall, Precision and Hausdorff distance (HD) of the proposed method are 0.8178, 0.8067, 0.8292 and 11.1367. Experimental results demonstrate that the proposed method offered improved segmentation results compared with existing deep learning-based methods.

6.
Sci Total Environ ; : 143076, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33129535

RESUMO

Vivianite (Fe3(PO4)2·8H2O) is a common hydrous ferrous phosphate mineral which often occurs in reductive conditions, especially anoxic non-sulfide environment containing high concentrations of ferrous iron (Fe2+) and orthophosphate (PO43-). Vivianite is an important product of dissimilatory iron reduction and a promising route for phosphorus recovery from wastewater. Its formation is closely related to the extracellular electron transfer (EET), a key mechanism for microbial respiration and a crucial explanation for the reduction of metal oxides in soil and sediments. Despite of the natural ubiquity, easy accessibility and attractive economic value, the application value of vivianite has not received much attention. This review introduces the characteristics, occurrence and biosynthesis of vivianite from microbial EET, and systematically analyzes the application value of vivianite in the environmental field, including immobilization of heavy metals (HMs), dechlorination of carbon tetrachloride (CT), sedimentary phosphorus sequestration and eutrophication alleviation. Additionally, its potential functions as a slow-release fertilizer are discussed as well. In general, vivianite is expected to make more contributions to the future scientific research, especially the solution of environmental problems. Overcoming the lack of understanding and some technical limitations will be beneficial to the further application of vivianite in environmental field.

7.
Sci Rep ; 10(1): 19055, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149232

RESUMO

Anemia is a hematological disorder that adversely affects the health of millions of people worldwide. Although many variables influence the development and exacerbation of anemia, one major contributing factor is the impairment of erythropoiesis. Normal erythropoiesis is highly regulated by the zinc finger transcription factor GATA-1. Disruption of the zinc finger motifs in GATA-1, such as produced by germline mutations, compromises the function of this critical transcription factor and causes dyserythropoietic anemia. Herein, we utilize a combination of in vitro and in vivo studies to provide evidence that arsenic, a widespread environmental toxicant, inhibits erythropoiesis likely through replacing zinc within the zinc fingers of the critical transcription factor GATA-1. We found that arsenic interacts with the N- and C-terminal zinc finger motifs of GATA-1, causing zinc loss and inhibition of DNA and protein binding activities, leading to dyserythropoiesis and an imbalance of hematopoietic differentiation. For the first time, we show that exposures to a prevalent environmental contaminant compromises the function of a key regulatory factor in erythropoiesis, producing effects functionally similar to inherited GATA-1 mutations. These findings highlight a novel molecular mechanism by which arsenic exposure may cause anemia and provide critical insights into potential prevention and intervention for arsenic-related anemias.

8.
Nurse Educ ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33186191
9.
Blood Press Monit ; 25(6): 372, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33156040
10.
Sci Rep ; 10(1): 19318, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168848

RESUMO

We studied the dissolution behavior of ß NaYF4:Yb(20%), Er(2%) UCNP of two different sizes in biologically relevant media i.e., water (neutral pH), phosphate buffered saline (PBS), and Dulbecco's modified Eagle medium (DMEM) at different temperatures and particle concentrations. Special emphasis was dedicated to assess the influence of different surface functionalizations, particularly the potential of mesoporous and microporous silica shells of different thicknesses for UCNP stabilization and protection. Dissolution was quantified electrochemically using a fluoride ion selective electrode (ISE) and by inductively coupled plasma optical emission spectrometry (ICP OES). In addition, dissolution was monitored fluorometrically. These experiments revealed that a thick microporous silica shell drastically decreased dissolution. Our results also underline the critical influence of the chemical composition of the aqueous environment on UCNP dissolution. In DMEM, we observed the formation of a layer of adsorbed molecules on the UCNP surface that protected the UCNP from dissolution and enhanced their fluorescence. Examination of this layer by X-ray photoelectron spectroscopy (XPS) and mass spectrometry (MS) suggested that mainly phenylalanine, lysine, and glucose are adsorbed from DMEM. These findings should be considered in the future for cellular toxicity studies with UCNP and other nanoparticles and the design of new biocompatible surface coatings.

11.
Mol Med Rep ; 22(6): 4579-4588, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33174051

RESUMO

FGD5 antisense RNA 1 (FGD5­AS1) is a long non­coding RNA in acute myocardial infarction (AMI), which is primarily caused by myocardial ischemia­hypoxia. Retinoid acid receptor­related orphan receptor α (RORA) is a key protector in maintaining heart function. However, the roles of FGD5­AS1 and RORA in AMI have not previously been elucidated. The present study investigated the effect and mechanism of FGD5­AS1 and RORA in human cardiomyocyte AC16 cells under hypoxia. Reverse transcription­quantitative PCR and western blotting demonstrated that FGD5­AS1 and RORA were downregulated in the serum of patients with AMI and hypoxia­challenged AC16 cells. Functional experiments were performed via assays, flow cytometry and western blotting. In response to hypoxia, superoxide dismutase (SOD) activity was inhibited, but apoptosis rate and levels of reactive oxygen species and malondialdehyde were promoted in AC16 cells, accompanied by increased Bax and cleaved caspase­3 expression levels, and decreased SOD2 and glutathione peroxidase 1 expression levels. However, hypoxia­induced oxidative stress and apoptosis in AC16 cells were attenuated by ectopic expression of FGD5­AS1 or RORA. Moreover, silencing RORA counteracted the suppressive role of FGD5­AS1 overexpression in hypoxic injury. FGD5­AS1 controlled RORA expression levels via microRNA­195­5p (miR­195), as confirmed by dual­luciferase reporter and RNA pull­down assays. Consistently, miR­195 knockdown suppressed hypoxia­induced oxidative stress and apoptosis in AC16 cells, which was abrogated by downregulating FGD5­AS1 or RORA. In conclusion, FGD5­AS1 modulated hypoxic injury in human cardiomyocytes partially via the miR­195/RORA axis, suggesting FGD5­AS1 as a potential target in interfering with the progression of AMI.

13.
Drug Saf ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180265

RESUMO

INTRODUCTION AND OBJECTIVE: Guidelines recommend combined doublet backbone chemotherapy based on 5-fluorouracil and oxaliplatin (OX) or irinotecan (IR) as the first-line treatment options for metastatic colorectal cancer. However, it is still unknown which is better when combined with bevacizumab (BEV). This systematic review and meta-analysis were performed to compare BEV-IR with BEV-OX regimens in terms of efficacy and safety. METHODS: We searched studies from databases including MEDLINE, EMBASE, CENTRAL, and conference papers. The outcomes were overall response rate, overall survival, progression-free survival, and the incidence of the most common adverse events. The dichotomous data were reported as the risk ratio (RR) and the survival outcomes were extracted as the hazard ratio with 95% confidence interval (CI). RESULTS: Eleven studies including 5632 patients were identified. No difference was found in overall survival or overall response rate between BEV-IR and BEV-OX regimens. The pooled progression-free survival was significantly longer in the BEV-IR group than the BEV-OX group (hazard ratio = 0.92, 95% CI 0.87-0.98, p = 0.08). Compared with the BEV-OX group, the BEV-IR group was related to a higher risk of bleeding events (RR = 0.80, 95% CI 0.64-0.98, p = 0.03), venous thromboembolism (RR = 0.60, 95% CI 0.46-0.79, p = 0.0002), and diarrhea (RR = 0.71, 95% CI 0.62-0.80, p < 0.00001). Conversely, the BEV-OX group was related to a higher risk of thrombocytopenia (RR 2.39, 95% CI 1.67-3.42, p < 0.00001) and neuropathy (RR 3.80, 95% CI 1.90-7.64, p = 0.0002). CONCLUSIONS: The BEV-IR regimen was superior in improving progression-free survival as the first-line treatment for metastatic colorectal cancer. The two different doublet regimens combined with BEV had their specific features of adverse events.

14.
Cell Transplant ; 29: 963689720965529, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33172291

RESUMO

Mesenchymal stromal cells (MSCs) are viewed as immune-privileged cells and have been broadly applied in allogeneic adoptive cell transfer for regenerative medicine or immune-suppressing purpose. However, the surface expression of human leukocyte antigen (HLA) class I molecules on MSCs could still possibly induce the rejection of allogeneic MSCs from the recipients. Here, we disrupted the ß2 microglobulin (B2M) gene in human peripheral blood mononuclear cell-derived induced pluripotent stem cells (iPSCs) with two clustered regulatory interspaced short palindromic repeat (CRISPR)-associated Cas9 endonuclease-based methods. The B2M knockout iPSCs did not express HLA class I molecules but maintained their pluripotency and genome stability. Subsequently, MSCs were derived from the HLA-negative iPSCs (iMSCs). We demonstrated that B2M knockout did not affect iMSC phenotype, multipotency, and immune suppressive characteristics and, most importantly, reduced iMSC immunogenicity to allogeneic peripheral blood mononuclear cells. Thus, B2M knockout iPSCs could serve as unlimited off-the-shelf cell resources in adoptive cell transfer, while the derived iMSCs hold great potential as universal grafts in allogeneic MSC transplantation.

15.
Life Sci ; : 118707, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33144187

RESUMO

Circular RNAs (circRNAs) are formed from the genome through diverse back splicing and feature the closed loop. circRNAs are widely available in a variety of cells and characterized by conservation, structural stability, high abundance and tissue-specific or developmental-specific expression. Recent studies have shown that circRNAs are closely related to liver diseases, such as metabolic-associated fatty liver disease, hepatitis, liver cirrhosis and hepatocellular carcinoma. circRNAs play an important role in the progression of liver diseases, are potential diagnostic and prognostic markers, and have translational value in therapy. This article reviews the research on circRNAs in liver diseases, with a view to providing a theoretical basis and new ideas for future research and treatment of liver diseases.

16.
J Geriatr Oncol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33160954

RESUMO

BACKGROUND AND PURPOSE: Comprehensive geriatric assessment (CGA) is a diagnostic method to assess the physical and mental health status of older patients. The purpose of this study was to assess the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer in older people who were classified as "fit" by CGA. The interim analysis focusing on safety was reported here as the first part of this trial. METHODS AND MATERIALS: This is a single arm, multicenter, phase II trial. The eligible patients for this study were aged 70 years or above that fulfilled the standard of intermediate or locally advanced risk category, and met the standard of fit (SIOG1) evaluated by CGA. All patients received preCRT (50 Gy) with Raltitrexed (3 mg/m2 on d1 and d22). Qualitative and quantitative variables were described using descriptive statistics. The surgery adherence predicting was analyzed by multivariate logistic regression. RESULTS: Thirty-nine fit patients were enrolled. All patients except one finished radiotherapy without dose reduction. Thirty-two patients finished the prescribed Raltitrexed therapy as scheduled. A serious toxicity was observed in 12 patients (30.8%), and only six patients (15.4%) experienced non-hematological side effects. CONCLUSION: Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.

17.
J Pharm Biomed Anal ; 193: 113636, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33221574

RESUMO

The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency.

18.
Blood Press Monit ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33164992

RESUMO

BACKGROUND: BMI and waist circumference (WC) have commonly been used to identify obesity in practice. The aim of the present study was to assess the blood pressure (BP) status among Chinese college students categorized by BMI and WC. METHODS: A total of 4226 college students (2107 males and 2119 females) aged 19-22 years included in the study. The WHO BMI cutoffs were used to define underweight, normal weight and overweight. The WC cutoffs (90 cm for man and 80 cm for woman) were used to define central obesity. High BP was defined as SBP/DBP ≥140/90 mmHg. The BP status of subjects within each category across BMI and WC were assessed. RESULTS: When subjects were categorized by BMI, overweight males and females had a higher prevalence of high BP than their nonoverweight counterparts. When WC was used to diagnose central obesity, subjects with central obesity had a higher prevalence of high BP than those with normal WC. A positive association between BMI, WC and BP was also observed even in normal-weight subjects, with 'high normal BMI' subgroup (BMI = 23.7-24.9) had a higher BP level and prevalence of high BP than 'low normal BMI' subgroups (BMI = 18.5-19.7 and BMI = 19.8-21.0, P < 0.05). CONCLUSION: Prevention of overweight/obesity in youth may be an effective approach for preventing the development of hypertension in the future; for normal-weight youth, it is essential to keep their BMI at a lower level within normal range.

19.
Cardiovasc Toxicol ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165770

RESUMO

Hypertension, as one of the major risk factors for cardiovascular disease, significantly affects human health. Prostaglandin E2 (PGE2) and the E3-class prostanoid (EP3) receptor have previously been demonstrated to modulate blood pressure and hemodynamics in various animal models of hypertension. The PGE2-evoked pressor and biochemical responses can be blocked with the EP3 receptor antagonist, L-798106 (N-[(5-bromo-2methoxyphenyl)sulfonyl]-3-[2-(2-naphthalenylmethyl) phenyl]-2-propenamide). In the hypothalamic paraventricular nucleus (PVN), sympathetic excitation can be introduced by PGE2, which can activate EP3 receptors located in the PVN. In such a case, the central knockdown of EP3 receptor can be considered as a potential therapeutic modality for hypertension management. The present study examined the efficacy of the PVN infusion of L-798106, by performing experiments on spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The rats were administered with chronic bilateral PVN infusion of L-798106 (10 µg/day) or the vehicle for 28 days. The results indicated that the SHRs had a higher mean arterial pressure (MAP), an increased Fra-like (Fra-LI) activity in the PVN, as well as a higher expression of gp91phox, mitogen-activated protein kinase (MAPK), and proinflammatory cytokines in the PVN compared with the WKYs. Additionally, the expression of Cu/Zn-SOD in the PVN of the SHRs was reduced compared with the WKYs. The bilateral PVN infusion of L-798106 significantly reduced MAP, as well as plasma norepinephrine (NE) levels in the SHRs. It also inhibited Fra-LI activity and reduced the expression of gp91phox, proinflammatory cytokines, and MAPK, whereas it increased the expression of Cu/Zn-SOD in the PVN of SHRs. In addition, L-798106 restored the balance of the neurotransmitters in the PVN. On the whole, the findings of the present study demonstrate that the PVN blockade of EP3 receptor can ameliorate hypertension and cardiac hypertrophy partially by attenuating ROS and proinflammatory cytokines, and modulating neurotransmitters in the PVN.

20.
Biomed Pharmacother ; 131: 110524, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152900

RESUMO

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine, commonly used to treat a variety of diseases. However, the hepatotoxicity associated with PM hampers its clinical application and development. In this study, we refined the zebrafish hepatotoxicity model with regard to the following endpoints: liver size, liver gray value, and the area of yolk sac. The levels of alanine aminotransferase, aspartate transaminase, albumin, and microRNAs-122 were evaluated to verify the model. Subsequently, this model was used to screen different extracts, components, and constituents of PM, including 70 % EtOH extracts of PM, four fractions from macroporous resin (components A, B, C, and D), and 19 compounds from component D. We found that emodin, chrysophanol, emodin-8-O-ß-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in PM, whereas polyphenols showed lower hepatotoxicity. To the best of our knowledge, this study is the first to identify that dianthrones may account for the hepatotoxicity of PM. We believe that these findings will be helpful in regulating the hepatotoxicity of PM.

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