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1.
Int Immunopharmacol ; 84: 106541, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32402950

RESUMO

OBJECTIVE: To illustrate the potential effects and mechanism of extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) on fibrosis in sclerodermatous chronic graft-versus-host-disease (cGVHD) models after allogeneic hematopoietic stem cell transplantation. METHODS: We first observed the therapeutic effects of MSC-EVs on a minor histocompatibility haploidentical model of sclerodermatous cGVHD and the function of MSC-EVs on skin fibrosis and macrophage activation and the related pro-fibrosis protein. Additionally, we observed the effects of MSC-EVs on B cells, the T follicular helper cell (TFH) and germinal center B cell (GC B cells) interaction and the ratio of B cell activation factor (BAFF) to B cells in vivo. RESULTS: MSC-EVs treatment could alleviate the cGVHD scores and fibrosis of skin in sclerodermatous cGVHD mice, and this was associated with a reduction macrophage percentage in the skin and spleen, and a reduction in macrophage infiltration and TGF-ß and smad2 production in the skin. Additionally, MSC-EVs influence B cells immune response by blocking the TFH/GC B cells interaction and reducing the ratio of BAFF to B cells in vivo. CONCLUSION: MSC-EVs prevent the fibrosis of sclerodermatous cGVHD mouse model by suppressing the activation of macrophages and B cells immune response.

2.
Chemosphere ; 253: 126592, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32289600

RESUMO

Prenatal exposure to particulate matter (PM) in ambient air has been linked to changes in newborn mitochondrial DNA copy number (mtDNAcn), but the effects of exposure are inconsistent. We aimed to investigate the effect of weekly PM exposure during pregnancy on newborn mtDNAcn. The present study included 762 mother-infant pairs who were recruited in a birth cohort established between November 2013 and March 2015 in Wuhan, China. Mother's prenatal daily exposure to PM2.5 and PM10 was calculated using a spatial-temporal land use regression model. Relative mtDNAcn in cord blood leukocytes was determined by quantitative real-time polymerase chain reaction. Distributive lag regression models (DLMs) were applied to estimate the association between PM exposure and newborn mtDNAcn. In the adjusted models, prenatal PM2.5 exposure during 25-32 weeks and PM10 exposure during 25-31weeks were significantly associated with decreased cord blood mtDNAcn. PM2.5 exposure during the third trimester was related to decreased mtDNAcn (cumulative percent change: -8.55%, 95% CI: -13.32%, -3.51%). We also identified other exposure windows (17-22 and 11-22 weeks) in which PM exposure was positively associated with mtDNAcn. Overall, exposure to particulate air pollution during mid-to-late gestation is significantly associated with alterations in newborn mtDNAcn, potentially suggesting an enhanced sensitivity to PM exposure during this period.

3.
Ann Nutr Metab ; 76(1): 54-61, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182619

RESUMO

INTRODUCTION: The role of tea consumption on rheumatoid arthritis (RA) has been studied in recent years, but no clear conclusion has been drawn as a result of small sample size of the studies or the fact that only in vitro studies have been performed. OBJECTIVES: The aim of this study was to explore the possible association of tea consumption with RA through a large-scale, real-world study. METHODS: A total of 733 RA patients were investigated from June to December, 2016. The disease activity of RA was assessed according to disease activity score 28-erythrocyte sedimentation rate. The amount and types of tea consumption were recorded by on-site self-administered questionnaires. Logistic regression models were applied to analyze the correlation between tea consumption and disease activity, adjusting for demographics, clinical and laboratory factors. RESULTS: There was an inverse association between tea consumption and disease activity in RA patients (OR 0.66, 95% CI 0.46-0.94). Compared with non-tea drinkers, a higher-intake of tea (>750 mL/day) was associated with lower disease activity of RA (OR 0.39, 95% CI 0.19-0.79), but not low-intake (≤750 mL/day; OR 0.83, 95% CI 0.42-1.63). A significant dose-response association was found between the amount of tea consumption and disease activity (p for trend <0.01). Further hierarchical regression analysis showed that such inverse associations were mainly present in female patients (p = 0.004), non-smokers (p = 0.01) or elders (≥60 years; p = 0.01). CONCLUSION: Tea consumption is associated with decreased disease activity of RA, suggesting the potential beneficial effect of tea in the disease.

4.
Mol Pharm ; 17(4): 1114-1126, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32176509

RESUMO

The efflux of anticancer agents mediated by P-glycoprotein (P-gp) is one of the main causes of multidrug resistance (MDR) and eventually leads to chemotherapy failure. To overcome this problem, the delivery of anticancer agents in combination with a P-gp inhibitor using nanocarrier systems is considered an effective strategy. On the basis of the physiological compatibility and excellent drug loading ability of erythrocytes, we hypothesized that nanoerythrocytes could be used for the codelivery of an anticancer agent and a P-gp inhibitor to overcome MDR in breast cancer. Herein, a folic acid-modified nanoerythrocyte system (PTX/TQR NPs@NanoRBC-PEG/FA) was prepared to simultaneously transport paclitaxel and tariquidar, and the in vitro and in vivo characteristics of this delivery system were evaluated through several experiments. The results indicated that the average diameter and surface potential of this nanocarrier system were 159.8 ± 1.4 nm and -10.98 mV, respectively. Within 120 h, sustained release of paclitaxel was observed in both pH 6.5 media and pH 7.4 media. Tariquidar release from this nanocarrier suppressed the P-gp function of MCF-7/Taxol cells and significantly increased the intracellular paclitaxel level (p < 0.01 versus the PTX group). The results of the MTT assay indicated that the simultaneous transportation of paclitaxel and tariquidar could significantly inhibit the growth of MCF-7 cells or MCF-7/Taxol cells. After 48 h of incubation with PTX/TQR NPs@NanoRBC-PEG/FA, the viability of MCF-7 cells and MCF-7/Taxol cells decreased to 7.37% and 30.2%, respectively, and the IC50 values were 2.49 µM and 6.30 µM. Pharmacokinetic results illustrated that, compared with free paclitaxel, all test paclitaxel nanoformulations prolonged the drug release time and showed similar plasma concentration-time profiles. The peak concentration (Cmax), area under the curve (AUC0-∞), and half-life (t1/2) of PTX/TQR NPs@NanoRBC-PEG/FA were 3.33 mg/L, 6.02 mg/L·h, and 5.84 h, respectively. Moreover, this active targeting nanocarrier dramatically increased the paclitaxel level in tumor tissues. Furthermore, compared with those of the other paclitaxel formulations, the cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels of the PTX/TQR NPs@NanoRBC-PEG/FA group increased by 1.38-fold (p < 0.01) and 1.36-fold (p < 0.01), respectively, and the activities of superoxide dismutase (SOD) and catalase (CAT) decreased to 67.8% (p < 0.01) and 65.4% (p < 0.001), respectively. More importantly, in vivo antitumor efficacy results proved that the PTX/TQR NPs@NanoRBC-PEG/FA group exerted an outstanding tumor inhibition effect with no marked body weight loss and fewer adverse effects. In conclusion, by utilizing the inherent and advantageous properties of erythrocytes and surface modification strategies, this biomimetic targeted drug delivery system provides a promising platform for the codelivery of an anticancer agent and a P-gp inhibitor to treat MDR in breast cancer.

6.
BMC Pulm Med ; 20(1): 68, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197604

RESUMO

BACKGROUND: Chronic cough has an important impact on physical, social and psychological aspects. A simple and effective method to assess different aspects of chronic cough severity is required. We aimed to develop a simple, self-completed test, Cough Evaluation Test (CET), to evaluate cough severity and its impact on health. METHOD: The items of preliminary CET were generated based on literature review and clinical practice. Items reduction was conducted by modified Delphi method. Patients with chronic cough were recruited to complete CET, Cough Visual Analog Scales (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Cough Symptom Score (CSS). Reassessments were performed at 1 week apart before treatment, and after more than 2 weeks treatments. Concurrent validation, internal consistency, repeatability, responsiveness and the minimal important difference (MID) were determined. RESULTS: CET consists of five items with a 5-point Likert scale (1-5 scaling of items, 5-25 score range). The Cronbach's alpha values for CET was 0.80. CET showed a stronger correlation with LCQ-MC (r = - 0.74) compared to that between LCQ-MC with VAS (r = - 0.61). CET also showed a stronger correlation with VAS (r = 0.70) compared to that between VAS with other measures. Intraclass correlation coefficients for CET was 0.84. In patients undergoing treatment, CET scores significantly changed (p < 0.0001). The MID of CET was 2. CONCLUSION: Cough Evaluate Test is a reliable, valid and responsive tool to simply evaluate impact of cough on physical, social and psychological aspects.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 56-62, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027253

RESUMO

OBJECTIVE: To investigate the expression and significance of B and T lymphocyte weakening factor (BTLA) in patients with chronic myelomonocytic leukemia (CMML). METHODS: Real-time PCR was used to detect the expression of BTLA and its ligand HVEM mRNA in 11 patients with chronic myelomonocytic leukemia and 11 normal donors. Flow cytometry was used to detect expression of BTLA and its HVEM on the cell surface of peripheral blood T lymphocytes and γδ T cells. RESULTS: The median values of BTLA and its ligand HVEM mRNA expression in peripheral blood of patients with CMML were 0.009% and 559.4%, respectively, which were significantly lower than those of normal controls (0.053% and 1031%)(P<0.001). The expression level of BTLA and HVEM on cell surface of peripheral lymphocytes was not significantly different from that in normal controls (P=0.3031 and 0.2576), however, the proportion of peripheral blood T lymphocytes in patients with CMML (median: 37.73%) was significantly lower than that in controls (median 69.23%)(P=0.0005). The expression of BTLA on the surface of γδ T cells in peripheral blood of patients with CMML (median: 23.26%) was significantly lower than that of the controls (median: 52.64%) (P<0.05), and there was no significant abnormality in HVEM expression (P=0.2791). CONCLUSION: The expression of BTLA and its ligand HVEM, the proportion of T lymphocytes and the expression of BTLA on the surface of γδ T cells in patients with CMML are reduced. The effects of these abnormalities on T cell function and prognosis and efficacy of patients need to be further observed.


Assuntos
Leucemia Mielomonocítica Crônica , Receptores Imunológicos/genética , Membro 14 de Receptores do Fator de Necrose Tumoral/genética , Humanos , Leucemia Mielomonocítica Crônica/genética , Ligantes , Linfócitos T
8.
Obes Surg ; 30(5): 2021-2025, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32078104

RESUMO

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is one of the most frequently performed bariatric procedures worldwide. Remnant gastric cancer after RYGB is a rare complication. There were about seventeen cases reported in the world. The location of the tumor in these cases occurs mainly in the gastric antrum, followed by the body, then the pylorus and linitis plastica, and the last was fundus of the stomach. To the best of our knowledge, this is the first case that gastric cancer located in the cardia of stomach after RYGB. CASE REPORT: A 68-year-old male patient had chronic esophagitis, bile reflux gastritis, and erosive antral gastritis 5 years after RYGB and now developed to aggressive carcinoma in the gastric pouch. In spite of having chemotherapy and traditional Chinese medicine therapy, the patient died of multiple organ failure after 15 months. CONCLUSIONS: This case report highlights the importance to have gastroscopy to observe the proximal small remnant stomach after RYGB in long-term follow-up. Attention must be paid when patients develop symptoms like abdominal pain or excessive weight loss after RYGB. For patients at high risk such as those who have a family history of gastric cancer or presenting abnormal levels of tumor markers should rather undergo Sleeve Gastrectomy plus Jejunojejunal Bypass (SGJB) instead of RYGB.

9.
Anal Chem ; 92(5): 3563-3571, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899867

RESUMO

Diacetoxyscirpenol (DAS) is a type A trichothecene mycotoxin with low molecular weight, and with respect to its toxicity and the occurrence in food and feed, it is known as a potential risk for public and animal health. In the present study, first, a sensitive and specific monoclonal antibody (5E7) was developed. Then, the antibody was applied to develop a competitive-type pressure-dependent immunosensor (CTPDI). The Au@PtNP was synthesized and labeled with goat antimouse antibody (Au@PtNPs-IgG). Finally, the concentration of DAS was negatively correlated with the pressure signal. In the presence of optimal conditions, matrix-matched calibration curves were plotted for wheat samples, in which an optimal IC50 value (half maximal inhibitory concentration) of 3.08 ng/g was achieved. The CTPDI was further applied to detect natural and blind wheat samples, and validation was carried out by liquid chromatography-tandem mass spectrometry. The results showed that CTPDI was highly appropriate and accurate for detection of DAS in wheat.

10.
Int J Mol Sci ; 21(2)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952330

RESUMO

Anoectochilus roxburghii is a traditional Chinese herb with high medicinal value, with main bioactive constituents which are flavonoids. It commonly associates with mycorrhizal fungi for its growth and development. Moreover, mycorrhizal fungi can induce changes in the internal metabolism of host plants. However, its role in the flavonoid accumulation in A. roxburghii at different growth stages is not well studied. In this study, combined metabolome and transcriptome analyses were performed to investigate the metabolic and transcriptional profiling in mycorrhizal A. roxburghii (M) and non-mycorrhizal A. roxburghii (NM) growth for six months. An association analysis revealed that flavonoid biosynthetic pathway presented significant differences between the M and NM. Additionally, the structural genes related to flavonoid synthesis and different flavonoid metabolites in both groups over a period of six months were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The results showed that Ceratobasidium sp. AR2 could increase the accumulation of five flavonol-glycosides (i.e., narcissin, rutin, isorhamnetin-3-O-beta-d-glucoside, quercetin-7-O-glucoside, and kaempferol-3-O-glucoside), two flavonols (i.e., quercetin and isorhamnetin), and two flavones (i.e., nobiletin and tangeretin) to some degrees. The qRT-PCR showed that the flavonoid biosynthetic genes (PAL, 4CL, CHS, GT, and RT) were significantly differentially expressed between the M and NM. Overall, our findings indicate that AR2 induces flavonoid metabolism in A. roxburghii during different growth stages, especially in the third month. This shows great potential of Ceratobasidium sp. AR2 for the quality improvement of A. roxburghii.

11.
Hypertens Res ; 43(5): 412-421, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31919480

RESUMO

Circulating saturated fatty acids (SFAs) have been associated with cardiovascular disease. However, little is known about the relationship of SFAs with the risk of pregnancy-induced hypertension (PIH). We conducted a nested case-control study to examine the associations between circulating SFAs and the risk of PIH. A total of 92 PIH cases were matched to 184 controls by age (±2 years) and infant sex from a birth cohort study conducted in Wuhan, China. Levels of circulating fatty acids in plasma were measured using gas chromatography-mass spectrometry. Conditional logistic regressions were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Even-chain SFAs, including myristic acid (14:0) and palmitic acid (16:0), were positively associated with the risk of PIH [ORs (95% CIs): 2.92 (1.27, 6.74) for 14:0 and 2.85 (1.18, 6.89) for 16:0, % by wt]. In contrast, higher levels of very-long-chain SFAs, including arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0), were associated with a lower risk of PIH [ORs (95% CIs): 0.40 (0.17, 0.92) for 20:0, 0.30 (0.12, 0.71) for 22:0 and 0.26 (0.11, 0.64) for 24:0, µg/mL]. For odd-chain SFAs, including pentadecanoic acid (15:0) and heptadecanoic acid (17:0), no significant difference was observed. Our results provided convincing evidence that different subclasses of SFAs showed diverse effects on the risk of PIH. This suggests that dietary very-long-chain SFAs may be a novel means by which to prevent hypertension. Future studies are required to confirm these associations and elucidate the underlying mechanisms.

12.
Obes Surg ; 30(2): 618-629, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31758470

RESUMO

BACKGROUND: Obesity has become a global epidemic. Surgical treatment of obesity and metabolic disorders in China is increasing rapidly, but it is still a new discipline even to health professionals. As an important member of the multidisciplinary team, the knowledge and attitudes of nurses provide crucial health care to the patients and support to surgeons. OBJECTIVES: To study the Chinese nurses' knowledge of obesity and metabolic disorders, and attitudes towards bariatric surgery and to improve their capability of work in this new discipline. METHODS: This is a multicenter study, with the questionnaire distributed to cooperative hospitals in the form of an electronic questionnaire by the First Affiliated Hospital of Jinan University in April 2018. A questionnaire was designed to investigate nurses' demographic, knowledge, and attitude towards obesity, weight loss, and bariatric surgery. RESULTS: A total of 5311 questionnaires were received, with an effective rate of 91.8% (4878 questionnaires); 65.2% of nurses had a normal BMI. Nurses generally had a high knowledge of obesity and related cardiovascular diseases (98.6%) and type 2 diabetes mellitus (90.2%). However, there was a lack of knowledge in other related aspects, for example its relations to carcinoma (49.5%), gastroesophageal reflux disease (40.1%), and psychological disorders (49.1%), which are controversial issues in bariatric surgery. It was found that education (p < 0.05) had an important influence to nurses' knowledge about the comorbidities of obesity. Female nurses had a higher tendency to choose weight loss than males, but male nurses did physical exercise more frequently than females (p < 0.05). Their acceptance of safety (25.1%) and efficacy (22.9%) of bariatric surgery is low, with concerns predominantly about postoperative complications and adverse effects. Surgical nurses had a more optimistic attitude towards surgery (p < 0.05). CONCLUSIONS: Chinese nurses have poor knowledge of obesity-related metabolic disorders and also have poor acceptance of surgical treatment modalities. Our findings suggest that it is crucial to enhance the continuing education of Chinese nurses for obesity, metabolic disorders, and bariatric surgery.

13.
Ther Adv Respir Dis ; 13: 1753466619891520, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31847717

RESUMO

BACKGROUND: Nonasthmatic eosinophilic bronchitis (NAEB) responds well to inhaled corticosteroids (ICS), while recurrence is common after discontinuing treatment. There are no data available to show whether treatment duration of ICS in patients with NAEB is related to recurrence. We aim to evaluate the effect of different duration of treatment with ICS on relapse of NAEB. METHODS: A total of 101 patients with NAEB were recruited to the open label, randomized, parallel-group trial. Patients were randomized to receive 1-month, 2-month, or 4-month treatment with inhaled budesonide (200 µg, twice daily). Sputum induction, cough visual analogue scale (VAS), and cough symptom score (CSS) were conducted at baseline and after completion of treatment. The patients were followed up for 1 year after treatment. The primary outcome was the relapse rate of NAEB in 1 year. RESULTS: ICS significantly decreased cough VAS, CSS, and sputum eosinophilia among these groups. There were no statistically significant between-group differences in cough VAS, CSS scores, and sputum eosinophil counts at the end of treatment, and no significant between-group differences in those changes from baseline to post-treatment. Significantly, more participants in the 1-month treatment group experienced a recurring episode of NAEB than those in the 3-month treatment group (41.9% versus 12.0%, p = 0.0137) at 1-year follow-up. The 2-month treatment group showed a lower tendency, with a relapse rate of 20.0% (p = 0.0644). CONCLUSIONS: Our results suggest that inhaled corticosteroids should be administrated for at least 2 months to reduce the relapse of NAEB. CLINICAL TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02002715). The reviews of this paper are available via the supplemental material section.

14.
J Hematol Oncol ; 12(1): 117, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747962

RESUMO

The original article [1] contains an error in authorship whereby author, Robert Weinkove's name is mistakenly inverted. The configuration noted in this Correction article should be considered instead along with author's updated affiliation.

15.
Dis Markers ; 2019: 2424751, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485275

RESUMO

Background: Renal fibrosis is a common outcome of all pathological types of chronic kidney disease (CKD). However, the noninvasive detection of renal fibrosis remains a challenge. Methods: We collected urine samples from 154 biopsy-proven IgA nephropathy (IgAN) patients and 61 healthy controls. The expression of mTOR was measured and the correlation with renal function parameter and pathological indicators. The receiver operating characteristic (ROC) curve for the diagnosis of IgAN and renal fibrosis was calculated. Results: The urinary mammalian target of rapamycin (mTOR) expression was decreased in IgAN patients. The expression of mTOR was correlated with serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, 24 h proteinuria, and cystatin C. Further, the urinary mTOR expression was significantly decreased in severe renal fibrosis patients compared with mild or moderate renal fibrosis patients. Urinary mTOR expression was correlated with score of tubulointerstitial fibrosis (TIF) and score of glomerular sclerosis. The ROC curve showed that mTOR can diagnose IgAN at a cut-off value of 0.930 with the sensitivity of 90.2% and specificity of 73.8% and renal fibrosis at a cut-off value of 0.301 with the sensitivity of 71.7% and specificity of 64.8%. Conclusion: Urinary mTOR mRNA expression was a potential biomarker for diagnosis of IgAN and renal fibrosis in IgAN patients.


Assuntos
Glomerulonefrite por IGA/urina , Serina-Treonina Quinases TOR/urina , Adulto , Biomarcadores/urina , Feminino , Fibrose , Glomerulonefrite por IGA/patologia , Humanos , Rim/metabolismo , Rim/patologia , Masculino
16.
Am J Transl Res ; 11(7): 4533-4541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396357

RESUMO

The aim of the present study was to conduct a retrospective analysis of efficacy and safety profiles of azacitidine (AZA) versus. decitabine (DAC) in Chinese patients with intermediate or higher-risk MDS, which was based on two clinical trials in a single center. A total of 40 included MDS patients diagnosed with refractory anemia with excess blast (RAEB) were from two independent clinic trials. Patients in each trial received either AZA (n = 19) or DAC (n = 21) respectively, and the effectiveness as well as the safety profile of the two drugs were compared. Patients treated with AZA showed a comparative efficacy to DAC group with regard to the overall response rate (73.7% versus. 76.2%, P = 0.86), overall survival (median: 19.3 versus. 20.8 months, P = 0.56), progression-free survival (median: 12.3 versus. 9.3 months, P = 0.43) and leukemia-free survival (median: 22.8 versus. 26.6 months, P = 0.62). Patients treated with DAC showed slightly higher incidence of severe hematological adverse events during the whole treatment. Comparing hematological AEs in each observation interval, a trend of higher percentage of neutropenia, leukopenia and anemia as well as treatment delays were seen during the first 6 cycles in the DAC group.

17.
J Sep Sci ; 42(19): 3095-3101, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31328867

RESUMO

Phthalate esters are easily released from plastics materials and migrate into the soil and water environment, causing serious pollution and posing a great threat to the health of human beings. A novel temperature-sensitive extractant combined with liquid-liquid microextraction was developed to preconcentrate three phthalates in the water environment. To optimize the extraction efficiency for the three phthalate esters, various parameters, including polymer molecular weight, salt type, salt addition, adsorption time, desorption solvent, desorption volume, and desorption time have been studied. Under optimal conditions, limits of detection and limits of quantification were in the range of 0.007-0.120 and 0.021-0.350 µg/L, respectively. Linearities varied in the range of 5-1000 µg/L, with the correlation coefficients of 0.9867-0.9997. The preconcentration factors were in the range of 25-75. The relative recoveries of the three phthalate esters were in the range of 82.2-105.6% at the spiked levels. The relative standard deviations were in the range of 0.7-9.2% based on triplicate measurements. The results indicate that the temperature-sensitive material is a good extractant for phthalate esters in water samples.

18.
Clin Transl Sci ; 12(6): 564-572, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31169344

RESUMO

In this paper, a special case for bioequivalence evaluation of oral formulations is discussed. Drug formulations with different forms of active moieties (e.g., free base and salt) may yield different dissolution characteristics and, thus, differ in absorption at elevated gastric pH. However, routine bioequivalence trials using subjects with normal gastric pH (i.e., ~ 1) may fail to identify these differences because dissolution/absorption profiles of the two formulations at normal gastric pH are similar. In the case of palbociclib, it is confirmedthat the free base and salt formulations showed different absorption in patients with different gastric pH. Significant reduction in drug absorption was observed only in patients with elevated gastric pH using free base formulation. The discovery that the free base had significantly reduced absorption hinged on the inclusion of enough patients with elevated gastric pH to detect a difference in a bioequivalence trial. This raises a concern, as demonstrated through simulation, that dissolution/absorption differences in other formulations could be missed in routine bioequivalence trials. Aside from differences in active pharmaceutical ingredients (APIs), other factors, such as changes in excipients or manufacturing methods, may also lead to exposure differences between formulations at elevated gastric pH. For formulations containing different forms of the same active moiety or the same API and showing different dissolution profiles at elevated pH (i.e., pH ~ 4-6.8), evaluation of bioequivalence with gastric pH modulators (e.g., a H2 blocker) in addition to routine bioequivalence assessments may help to ensure therapeutic equivalence in patients with elevated gastric pH.

19.
Int Immunopharmacol ; 74: 105663, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31200338

RESUMO

Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSC-EVs) are taken more seriously as immunomodulatory and anti-inflammatory agents. We studied the therapeutic effects of MSC-EVs on allergic contact dermatitis (ACD), a typical T cell-mediated disorder. A contact hypersensitivity (CHS) mouse model for ACD was established and treated by intravenous MSC-EVs injection. We found that human umbilical cord MSC-EVs could significantly prevent the pathology of CHS, including reduced ear swelling and leukocyte infiltration. Injection of MSC-EVs significantly inhibited CD8+IFN-γ+ cytotoxic T (Tc1) cells and CD4+IFN-γ+ type 1 helper T (Th1) cells, and reduced the level of pro-inflammatory Tumor Necrosis Factor-alpha (TNF-α) and interferon gamma (IFN-γ), and induced CD4+CD25+Foxp3+ regulatory T cells (Tregs) and the level of anti-inflammatory IL-10. In vitro, MSC-EVs also suppressed Tc1 and Th1 cells and induced Tregs and the related cytokines, further indicating the immune regulatory role of MSC-EVs. Interestingly, PKH26-labeled MSC-EVs were found to be directly internalized by CD3+ T cells, resulting in reduced signal transducer and activator of transcription 1 (STAT1) protein levels in vitro. In summary, MSC-EVs can prevent the onset of CHS by inhibiting Tc1 and Th1 immune responses and inducing the Tregs phenotype in vivo and in vitro. The mechanism by which MSC-EVs influence CD3+ T cells might partially involve targeting STAT1 in vitro. Therefore, MSC-EVs are ideal candidates for cell-free immunomodulatory therapy for T cell-mediated diseases such as ACD.


Assuntos
Dermatite de Contato/imunologia , Vesículas Extracelulares/imunologia , Leucócitos Mononucleares/imunologia , Células-Tronco Mesenquimais/imunologia , Linfócitos T/imunologia , Animais , Citocinas/genética , Citocinas/imunologia , Humanos , Masculino , Camundongos Endogâmicos BALB C
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 221: 117211, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31158765

RESUMO

Doping graphene quantum dots (GQDs) with heteroatoms can change their band gap and electronic density, thus enhancing their fluorescence quantum yield (QY). In this work, we for the first time reported a nontoxic, rapid, and one-pot hydrothermal method to synthesize sulfur and phosphorus co-doped GQDs (S, P-GQDs). Citric acid was functioned as a carbon source, whereas sodium phytate and anhydrous sodium sulfate are used as the P and S sources, respectively, in this bottom-up synthesis. The resulting S, P-GQDs exhibit high heteroatomic doping ratios of 9.66 at.% for S and 3.34 at.% for P, and higher QY than those obtained from monoatomic doped GQDs. Additionally, the as-prepared S, P-GQDs exhibit excitation-dependent behavior, pH sensitivity between 8.0 and 13.0, high tolerance of ionic strength. More importantly, the as-synthesized S, P-GQDs show a sensitive and selective behavior for sensing nitrite (NO2-) in the concentration range of 0.7-9 µmol/L, and the detection limit was as low as 0.3 µmol/L. Additionally, the S, P-GQDs was successfully used in detecting NO2- in pickled foods, showing their promise for potential applications in realistic analysis.


Assuntos
/análise , Análise de Alimentos/métodos , Nitritos/análise , Pontos Quânticos/química , Ácido Cítrico/química , Grafite/química , Microscopia Eletrônica de Transmissão , Concentração Osmolar , Fósforo/química , Fotodegradação , Ácido Fítico/química , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Sulfatos/química , Enxofre/química
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