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1.
J Clin Periodontol ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32017185

RESUMO

AIM: To investigate the role of platelets during the development of ligature-induced experimental periodontitis in mice. MATERIALS AND METHODS: Experimental periodontitis was induced by placement of sterilized 5-0 cotton ligatures around the maxillary and mandibular second molars of C57BL/6 wild-type mice. Flow cytometry was used to analyse platelet activation and platelet-leukocyte aggregate formation, and histologic analysis was used to evaluate inflammation and localization of platelets and leukocytes in periodontal tissues during the development of experimental periodontitis and in experimental periodontitis with and without antiplatelet drug treatment. RESULTS: Experimental periodontitis induced platelet activation and platelet-leukocyte interaction. Platelets and leukocytes gradually infiltrated in inflammatory gingival tissues during the development of experimental periodontitis. The inhibition of platelet activation via drug therapy led to significant inhibition of leukocyte migration and marked reduction in periodontal inflammation. CONCLUSION: This study revealed that platelets are critical for inflammation and tissue injury in periodontitis and serve as mediators of inflammation in periodontal tissue.

2.
Nature ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015507

RESUMO

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (2019-nCoV) which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started from 12 December 2019, has caused 2,050 laboratory-confirmed infections with 56 fatal cases by 26 January 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The 2019-nCoV virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

3.
Biomed Environ Sci ; 33(1): 11-18, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32029054

RESUMO

Objectives: The aims of this study were to assess the associations between parity and metabolic syndrome (MetS) and its components and to evaluate the effects of body mass index (BMI) on these associations. Methods: A total of 5,674 women were enrolled from Jidong and Kailuan communities (Tangshan, Hebei) in Northern China. All participants completed standardized questionnaires, physical examination, and biochemical measurements. Logistic regression analysis was used to test the associations. Results: Compared with women with parity of one, nulliparous women had decreased odds ratios ( ORs ); those with parity of two had odds of abdominal obesity [ OR= 1.45, 95% confidence interval ( CI) 1.17-1.81, P < 0.001], high blood pressure ( OR= 1.26, 95% CI: 1.03-1.54, P = 0.025), elevated fasting glucose levels ( OR= 1.36, 95% CI: 1.03-1.79, P = 0.029), and MetS ( OR= 1.39, 95% CI: 1.13-1.73, P = 0.002); and those with parity of three or more had increased odds of elevated triglyceride levels ( OR= 1.42, 95% CI: 1.04-1.94, P = 0.027) and MetS ( OR= 1.50, 95% CI: 1.10-2.05, P = 0.011) after complete adjustment for confounders. Furthermore, BMI and age subgroups partially modified the associations between parity and MetS and its components. Conclusions: Parity is positively associated with MetS and select components in women. BMI is an important modifier involved in the associations between parity and MetS.

4.
Ann Transplant ; 25: e920224, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32029699

RESUMO

BACKGROUND ABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China. MATERIAL AND METHODS We developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared. RESULTS Between September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100-500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1-5), which was conducted between days -10 and -1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients. CONCLUSIONS Our individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.

5.
J Chromatogr A ; : 460913, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32007220

RESUMO

Traditional boron affinity materials usually capture cis-diol-containing molecules under alkaline condition, but some cis-diol-containing molecules, such as polyphenols, are unstable and easy to be oxidized and degraded under alkaline condition. Teamed boronate affinity (TBA) can specifically capture cis-diol-containing molecules under neutral condition. However, the report about combination of TBA and magnetic nanoparticle for the extraction was rare. Here, we fabricated two kinds of teamed boronate affinity magnetic nanoparticles (TBAMP), including Fe3O4@TBAP and Fe3O4@SiO2@TBAP. Adsorption capacities of cis-diol-containing molecules on the latter were similar to these on the former, but the latter possessed more superior regeneration performance than the former. Therefore, the TBAMP with more superior regeneration performance was used as magnetic solid-phase extraction (MSPE) adsorbent for capturing polyphenols under neutral condition. The TBAMP MSPE was optimized in detail, and combined with high-performance liquid chromatography-mass spectrometry (HPLC-MS) for the simultaneous determination of 13 kinds of polyphenols from Flos Lonicerae Beverage. The proposed method showed low limit of detection between 0.01 and 0.20 ng mL-1. In blank Flos Lonicerae Beverage, 11 kinds of polyphenols ranged from 0.54 ng mL-1 to 52.99 ng mL-1 were detected. In the standard addition method, recoveries of cis-diol-containing polyphenols were between 85.7% and 102.1% with intra-day and inter-day relative standard deviation ranging from 3.2% to 5.1% and 5.3% to 7.3%, respectively.

6.
Vet Microbiol ; 240: 108511, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31902508

RESUMO

Since late 2010, highly virulent PEDV G2-genotype strains have emerged globally extracting heavy losses on the pork industries of numerous countries. We investigated the characteristics of a field strain of PEDV (PEDV strain SH) isolated from a piglet with severe diarrhea on a farm in Shanghai China. Whole genome sequencing and analysis revealed that the SH strain belonged to subtype G2b and has a unique 12-aa deletion (aa 399-410) including the antigenic epitope NEP-1C9 (aa 398-406) of the N protein. PEDV SH strain is highly pathogenic to challenged newborn piglets, resulting in 100 % morbidity and mortality. Pathological examination revealed significant villus atrophy in the jejuna of infected piglets. Mice inoculated with inactivated PEDV SH produced antibodies against the N protein, but no antibodies against the deletions. These results illustrated that deletion of the NEP-1C9 epitope had no effect on the immunogenicity or pathogenicity of PEDV, providing evidence of the necessity to monitor the genetic diversity of the virus. Our study also contributes to development of candidate for vaccines and diagnostics that could differentiate pigs seropositive due to vaccination by conventional strains from wild virus infection.

7.
Chin Med J (Engl) ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31996543

RESUMO

BACKGROUND: In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension. METHODS: In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 µg norepinephrine (group N; n = 52) or 100 µg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well. RESULTS: Compared to group P, women in group N had a higher CO (standardized CO 5.8 ±â€Š0.9 vs. 5.3 ±â€Š1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ±â€Š17.2 vs. 60.0 ±â€Š13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ±â€Š174 vs. 996 ±â€Š182 dyne·s/cm, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ±â€Š11.6 vs. 75.0 ±â€Š7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05). CONCLUSIONS: Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

8.
ACS Nano ; 14(1): 476-487, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31895530

RESUMO

Viruses are associated with up to 15% of human cancer. MicroRNAs (miRNAs) encoded by numerous oncogenic viruses including Kaposi's sarcoma-associated herpesvirus (KSHV) play significant roles in regulating the proliferation and survival of virus-induced cancer cells, hence representing attractive therapeutic targets. Here, we report that specific inhibition of viral miRNAs by carbon dots (Cdots)-mediated delivery of locked nucleic acid (LNA)-based suppressors inhibit the proliferation of KSHV-associated primary effusion lymphoma (PEL) cells. Specifically, a combination of Cdots-LNAs to knock down the levels of KSHV miR-K12-1, miR-K12-4, and miR-K12-11 induces apoptosis and inhibits proliferation of PEL cells. Significantly, these Cdots-LNAs effectively inhibit the initiation of PEL and regress established PEL in a xenograft mouse model. These results demonstrate the feasibility of using Cdots to deliver miRNA suppressors for targeting viral cancers. Our study with viral miRNAs as targets may provide the scientific basis for using antisense drugs for human cancers associated with oncogenic viruses.

9.
Trials ; 21(1): 113, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992331

RESUMO

BACKGROUND: Periodontal diseases are regarded as the most common diseases of mankind. The prevalence rate of periodontal disease assumes a clear growth tendency, increasing by 57.3% from 1990 to 2010. Thereby, effective periodontal therapy is still a long-term task and a difficult problem. The goals of periodontal therapy are to eliminate the infectious and inflammatory processes of periodontal diseases. Root planing, in order to eliminate the "infected cementum," has been an important step in the treatment of periodontitis since the 1970s. However, along with the understanding of the effects of endotoxin on the root surface, the necessity of manual root planing has been gradually queried. Ultrasonic instruments, which are more recent innovations, would not remove the cementum excessively, and are also more time-saving and labor-saving compared to using hand instruments. Hence, an increasing number of dentists prefer to do scaling with ultrasonic instruments only. However, the necessity of root planing remains emphasized in the international mainstream views of periodontal mechanical treatment. Therefore, this study is devoted to compare the clinical effect of ultrasonic subgingival debridement and ultrasonic subgingival scaling combined with manual root planing, which takes the implementation of root planing as the only variable and is more in line with the current clinical situation, thus hoping to provide some valuable reference to dentists. METHODS/DESIGN: Forty adult patients who fit the inclusion criteria are being recruited from the Peking University Hospital of Stomatology (Beijing, China). By means of randomization tables, one quadrant of the upper and lower teeth is the test group and the other is the control group. Test group: ultrasonic subgingival scaling combined with manual root planing. CONTROL GROUP: ultrasonic subgingival debridement. In a 24-week follow-up period, plaque index, probing depth, clinical attachment loss, bleeding index, furcation involvement, mobility, and patient-reported outcome (Visual Analog Scale for pain and sensitivity) will be observed and documented. DISCUSSION: This study evaluates the effectiveness of ultrasonic subgingival scaling combined with manual root planing and ultrasonic subgingival debridement alone in the nonsurgical treatment of periodontitis with a split-mouth design after 1, 3 and 6 months. The result of the trial should potentially contribute to an advanced treatment strategy for periodontitis with an ideal clinical outcome. TRIAL REGISTRATION: International Clinical Trials Registry Platform (ICTRP), ID: ChiCTR1800017122. Registered on 12 July 2018.

10.
Sci Rep ; 10(1): 560, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953417

RESUMO

The aim of current study was to use competing risk model to assess whether medullary carcinoma of the breast (MCB) has a better prognosis than invasive ductal carcinomas of breast cancer (IDC), and to build a competing risk nomogram for predicting the risk of death of MCB. We involved 3,580 MCB patients and 319,566 IDC patients from Surveillance, Epidemiology, and End Results (SEER) database. IDC was found to have a worse BCSS than MCB (Hazard ratio (HR) > 1, p < 0.001). The 5-year cumulative incidences of death (CID) was higher in IDC than MCB (p < 0.001). Larger tumor size, increasing number of positive lymph nodes and unmarried status were found to worsen the BCSS of MCB (HR > 1, p < 0.001). We found no association between ER, PR, radiotherapy or chemotherapy and MCB prognosis (p > 0.05). After a penalized variable selection process, the SH model-based nomogram showed moderate accuracy of prediction by internal validation of discrimination and calibration with 1,000 bootstraps. In summary, MCB patients had a better prognosis than IDC patients. Interestingly, unmarried status in addition to expected risk factors such as larger tumor size and increasing number of positive lymph nodes were found to worsen the BCSS of MCB. We also established a competing risk nomogram as an easy-to-use tool for prognostic estimation of MCB patients.

11.
Anesth Analg ; 130(2): 505-517, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31934908

RESUMO

BACKGROUND: A prolonged exposure to ketamine triggers significant neurodegeneration and long-term neurocognitive deficits in the developing brain. Monosialotetrahexosylganglioside (GM1) can limit the neuronal damage from necrosis and apoptosis in neurodegenerative conditions. We aimed to assess whether GM1 can prevent ketamine-induced developmental neurotoxicity. METHODS: Postnatal day 7 (P7) rat pups received 5 doses of intraperitoneal ketamine (20 mg/kg per dose) at 90-minute intervals for 6 hours. Cognitive functions, determined by using Morris water maze (MWM) including escape latency (at P32-36) and platform crossing (at P37), were compared among the ketamine-exposed pups treated with or without exogenous GM1 (30 mg/kg; n = 12/group). The effect of GM1 on apoptosis in hippocampus was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining and activated caspase 3 measurement. The hippocampal expression of brain-derived neurotrophic factor (BDNF), along with the phosphorylation of protein kinase B (AKT) and extracellular signal-related kinases 1 and 2 (ERK1/2), was detected by western blotting (n = 6/group). Anti-BDNF antibody (2 µg per rat) administered before GM1 treatment was applied to determine the neuroprotective mechanisms of GM1. RESULTS: The rats receiving ketamine exposure experinced cognitive impairment in MWM test compared to the control rats, indicated by prolonged escape latency at P34 (P = .006), P35 (P = .002), and P36 (P = .005). However, in GM1-pretreated rats, ketamine exposure did not induce prolonged escape latency. The exogenous GM1 increased the platform-crossing times at P37 (3.00 ± 2.22 times vs 5.40 ± 1.53 times, mean ± standard deviation; P = .041) and reduced the hippocampal TUNEL-positive cells and cleaved-caspase 3 expression in ketamine-exposed young rats. Ketamine decreased BDNF expression and phosphorylation of AKT and ERK in the hippocampus, whereas exogenous GM1 blocked these ketamine-caused effects. However, for the ketamine-exposed rat pups receiving exogenous GM1, compared to immunoglobulin Y (IgY) isotype control, the BDNF-neutralizing antibody treatment counteracted the exogenous GM1-induced improvement of the escape latency at P36 (41.32 ± 12.37 seconds vs 25.14 ± 8.97 seconds, mean ± standard deviation; P = .036), platform-crossing times at P37 (2.16 ± 1.12 times vs 3.92 ± 1.97 times, mean ± standard deviation; P < .036), apoptotic activity, as well as AKT and ERK1/2 phosphorylation in the hippocampus of ketamine-challenged young rats. CONCLUSIONS: Our data suggest that the exogenous GM1 acts on BDNF signaling pathway to ameliorate the cognitive impairment and hippocampal apoptosis induced by ketamine in young rats. Our study may indicate a potential use of GM1 in preventing the cognitive deficits induced by ketamine in the young per se.

12.
Chin J Integr Med ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31919749

RESUMO

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

13.
Immunol Res ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919790

RESUMO

The Cluster of differentiation 226(CD226)/T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif domain (TIGIT) axis plays an important role in the balance of the immune response. A previous study showed that CD226 is involved in CD4+ T cell differentiation and that blocking CD226 may attenuate experimental autoimmune encephalomyelitis (EAE) development. However, the molecular mechanisms underlying this process remain incompletely understood. In this study, it was found that Cd226-/- mice were less susceptible to EAE and that there was less T helper 17(Th17) cell infiltration with higher levels of regulatory cells (Tregs) infiltration in the Cd226-/- EAE mouse central nervous system (CNS) compared with that in the WT EAE mouse CNS. Moreover, the suppressive function of Cd226-/- Tregs was upregulated compared with that of WT Tregs. Furthermore, it was observed that the expression levels of CTLA-4 and TIGIT on Cd226-/- Tregs were higher than those on WT Tregs during EAE in the spleen and CNS. Our results demonstrate a pivotal role for CD226 in attenuating Treg function in EAE that was associated with downregulating the expression levels of CTLA-4 and TIGIT.

14.
Biomaterials ; 230: 119650, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31806404

RESUMO

A multitude of micro- and nano-surface structures have been developed to improve the clinical performance of endosseous titanium (Ti) implants. However, most of these surface structures only simulate the topographic elements on a micro- or nano-scale. In this study, a nano-micro hierarchical TiO2 clustered nanotubular structure was fabricated using anodization, and then functionalized with platelet derived growth factor-BB (PDGF-BB) using PhoA (11-hydroxyundecylphosphonic acid)/CDI (carbonyldiimidazole) chemistry. The resulting 3-dimensional spatial biomimetic structure, named NTPCP, exhibited negligible cytotoxicity and satisfactory bio-activity for host cells, and significantly enhanced the attachment as well as osteogenesis-related functions (early-stage proliferation, extracellular matrix synthesis and mineralization) of human bone marrow mesenchymal stem cells (bMSCs). We observed drastically elevated expression of osteocalcin (OCN), which mirrored prominent bone formation around the NTPCP implants in a rat model. This study establishes a novel strategy to improve the osseointegration of endosseous Ti implants via surface nano-topographic modification and bio-factor covalent functionalization.

15.
Aesthetic Plast Surg ; 44(1): 89-92, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696242

RESUMO

OBJECTIVE: To study the anatomical location of retro-orbicularis oculi fat (ROOF) in the upper eyelid and to investigate how ROOF affects the appearance of the upper eyelid. METHODS: Twenty-eight Chinese hemifacial cadaver specimens were used (14 male cadavers; age range 52-82 years). In 28 hemifaces, the eyelids were dissected from the superficial to deep layers, and the appearance, location, extent, and surrounding tissue of ROOF were observed. Additionally, we observed the relationship between the upper eyelid morphology and ROOF of the upper eyelid in surgical patients who were treated in the plastic surgery department of Tongji Hospital affiliated with Huazhong University of Science and Technology in 2018. RESULTS: ROOF is a type of fascia adipose tissue that is located in a fat compartment between the muscles (the orbicularis oculi and frontalis muscles) and the orbital septum/frontalis fascia. In patients with hypertrophic ROOF, the upper eyelid appears as a heavy eyelid and as a drooping eyelid. And in patients with atrophic ROOF, the upper eyelid appears as a sunken eyelid. CONCLUSION: ROOF is located in the fat compartment between the orbicularis muscle and the orbital septum/frontalis fascia. ROOF covers the entire upper eyelid and appears thinner medially and thicker laterally. It is continuous with the fat under the frontalis muscle and affects the appearance of the upper eyelid. It represents an important factor in upper eyelid surgery. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

16.
Plant Physiol Biochem ; 146: 98-111, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734522

RESUMO

Drought stress is the primary factor limiting the growth and fruit quality of grapevines worldwide. However, the biological function of the NAC [No apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), Cup-shaped cotyledon (CUC)] transcription factor (TF) in grapevine is not clear. In this study, we reported that VvNAC17, a novel NAC transcription factor, was expressed in various tissues following drought, high temperature (45 °C), freezing (4 °C), salicylic acid (SA), and abscisic acid (ABA) treatments in grapevine. The VvNAC17 protein was localized in the nucleus of Arabidopsis thaliana protoplasts and demonstrated transcriptional activation activities at its C-terminus in yeast. The VvNAC17 gene was overexpressed in Arabidopsis thaliana. Under mannitol and salt stress, the germination rates of the VvNAC17-overexpression lines were higher than those of the wild-type plants, as were the root lengths. The VvNAC17-overexpression lines showed greater tolerance to freezing stress along with a higher survival rate. Following ABA treatment, the seed germination rate and the root length of the VvNAC17-overexpression lines were inhibited, and the stomatal opening and stomatal density were reduced. When subjected to drought and dehydration stress, the VvNAC17-overexpression lines showed improved survival and reduced water loss rates in comparison to the wild-type plants. Under drought conditions, the VvNAC17-overexpression lines had lower malondialdehyde and H2O2 contents, but higher peroxidase, superoxide dismutase, and catalase activities as well as higher proline content. Moreover, the expression of marker genes, including ABI5, AREB1, COR15A, COR47, P5CS, RD22, and RD29A, was up-regulated in the VvNAC17-overexpression lines when subjected to ABA and drought treatments. The results suggest that in transgenic Arabidopsis over-expression of VvNAC17 enhances resistance to drought while up-regulating the expression of ABA- and stress-related genes.

17.
Acta Pharmacol Sin ; 41(1): 47-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31607752

RESUMO

T cell metabolic activation plays a crucial role in inflammation of atherosclerosis. Shikonin (SKN), a natural naphthoquinone with anti-inflammatory activity, has shown to exert cardioprotective effects, but the effect of SKN on atherosclerosis is unclear. In addition, SKN was found to inhibit glycolysis via targeting pyruvate kinase muscle isozyme 2 (PKM2). In the present study, we investigated the effects of SKN on hyperhomocysteinemia (HHcy)-accelerated atherosclerosis and T cell inflammatory activation in ApoE-/- mice and the metabolic mechanisms in this process. Drinking water supplemented with Hcy (1.8 g/L) was administered to ApoE-/- mice for 2 weeks and the mice were injected with SKN (1.2 mg/kg, i.p.) or vehicle every 3 days. We showed that SKN treatment markedly attenuated HHcy-accelerated atherosclerosis in ApoE-/- mice and significantly decreased inflammatory activated CD4+ T cells and proinflammatory macrophages in plaques. In splenic CD4+ T cells isolated from HHcy-ApoE-/- mice, SKN treatment significantly inhibited HHcy-stimulated PKM2 activity, interferon-γ secretion and the capacity of these T cells to promote macrophage proinflammatory polarization. SKN treatment significantly inhibited HHcy-stimulated CD4+ T cell glycolysis and oxidative phosphorylation. Metabolic profiling analysis of CD4+ T cells revealed that Hcy administration significantly increased various glucose metabolites as well as lipids and acetyl-CoA carboxylase 1, which were reversed by SKN treatment. In conclusion, our results suggest that SKN is effective to ameliorate atherosclerosis in HHcy-ApoE-/- mice and this is at least partly associated with the inhibition of SKN on CD4+ T cell inflammatory activation via PKM2-dependent metabolic suppression.

18.
J Chromatogr A ; 1609: 460448, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31421793

RESUMO

In this work, we reported a simple two-step method for the synthesis of magnetic mesoporous epoxy resin (MMER), including one-pot template-free hydrothermal synthesis of nanoscale amine-functionalized magnetic nanoparticles (MN-NH2) and initiator-free ring-opening polymerization of epoxy resin. The resultant MMER was characterized in detail by transmission electron microscope (TEM), Fourier transform-infrared (FT-IR) spectra, X-ray photoelectron spectroscopy (XPS), thermogravimetic analysis (TGA) and magnetization curves. These results demonstrated successful synthesis of MMER with sufficient magnetic property and excellent thermal stability. The epoxy resin was covalent bonding MN-NH2 on and synthesized by hydrophobic monomers, so the MMER exhibited excellent adsorption quantity for hydrophobic bile acids. The MMER was used as magnetic solid-phase extraction (MSPE) sorbent, and combined with liquid chromatography-tandem mass spectrometry to extract and monitor 11 kinds of bile acids from serum sample. The proposed MSPE combined with LC-MS/MS method exhibited low limit of detection between 0.1 and 5 ng mL-1. In blank serum sample, 9 kinds of bile acids were detected, and ranged from -2.29 ng mL-1 to 6.86 ng mL-1. In standard addition recovery test, the recovery values of detectable bile acids ranged 102.4% to 108.5%, 96.0% to 104.0% and 82.3% to 103.3% when spiked with 0.2, 2.0 and 20 ng mL-1, respectively. The intra- and inter-day precision (n = 6) ranged 3.7% to 5.9% and 7.0% to 9.5%, respectively. The above results demonstrated that the MSPE combined with LC-MS/MS method was accurate and effective for quantitative determination of bile acids from complex biological samples.

19.
J Chromatogr A ; 1609: 460510, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31515077

RESUMO

In this study, a novel phenyl-boronic acid polymeric monolith (PBAPM) in polyether ether ketone (PEEK) tube was fabricated. The inner wall of PEEK tube was modified with mussel inspired polydopamine layer to firmly bond PBAPM, so as to avoid the outflow of PBAPM from PEEK tube and improve the service life and application scope of PBAPM. The PBAPM was synthesized by initiator-free ring-opening polymerization based on our previous work. The boric acid groups provided B-N coordination sites, as well as the hydrophobic amino and epoxy monomers provided hydrophobic interaction sites. Due to the synergistic effect of hydrophobic interaction and B-N coordination, the PBAPM exhibited excellent binding amounts for nitrogen-containing sulfonamides (SAs). In addition, the PBAPM possessed excellent stability, rigidity and permeability. Therefore, the PBAPM was used as solid phase microextraction (SPME) material for enrichment and separation of SAs from aqueous samples. The PBAPM SPME was optimized in detail, and combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for simultaneous determination of 10 kinds of SAs from tap, lake and river water. Using only 1 mL of water samples, limit of quantitation of SAs could reach 0.54-4.5 ng L-1. Recoveries of standard spiked SAs from water samples were between 82.0% and 105.4%, with intra-day and inter-day relative standard deviation ranging from 3.3% to 5.6% and 4.2% to 8.1%, respectively. The PBAPM SPME combined with UPLC-MS/MS method shown better or similar recoveries, and used fewer samples than previous methods. These results demonstrated that the PBAPM could selectively separate and enrich ultra-trace nitrogen-containing SAs from aqueous samples.

20.
CNS Neurosci Ther ; 26(1): 55-65, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31087449

RESUMO

BACKGROUND: Neural stem cells (NSCs) transplantation is considered a promising treatment for Parkinson's disease. But most NSCs are differentiated into glial cells rather than neurons, and only a few of them survive after transplantation due to the inflammatory environment. METHODS: In this study, neural stem cells (NSCs) and microglial cells both forced with the Nurr1 gene were transplanted into the striatum of the rat model of PD. The results were evaluated through reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunofluorescence analysis. RESULTS: The behavioral abnormalities of PD rats were improved by combined transplantation of NSCs and microglia, both forced with Nurr1. The number of tyrosine hydroxylase+ cells in the striatum of PD rats increased, and the number of Iba1+ cells decreased compared with the other groups. Moreover, the dopamine neurons differentiated from grafted NSCs could still be detected in the striatum of PD rats after 5 months. CONCLUSIONS: The results suggested that transplantation of Nurr1-overexpressing NSCs and microglia could improve the inhospitable host brain environments, which will be  a new potential strategy for the cell replacement therapy in PD.

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