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1.
Biomed Pharmacother ; 121: 109588, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707350

RESUMO

Translocator protein (TSPO) is highly expressed in the cardiovascular system, exerting crucial effects on both myocardial damage and protection. However, the role and mechanism of TSPO in myocardial ischemia/reperfusion (I/R) injury remains elusive. In the current study, we subjected H9c2 cardiomyocytes to anoxia/reoxygenation (A/R) and knocked down TSPO expression by RNA interference to investigate the possible mechanism of TSPO on I/R injury. TSPO expression in cardiomyocytes was up-regulated when exposed to A/R, but normal in anoxic preconditioned (APC) cardiomyocytes. Moreover, A/R also led to an increase in reactive oxygen species (ROS), oxidative stress aggravation, mitochondrial membrane potential collapse, mitochondrial permeability transition pore (mPTP) opening, and cell apoptosis. However, these events were completely compensated by downregulating TSPO expression. TSPO-downregulated cardiomyocytes produced lesser lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and showed lesser cytosol malondialdehyde (MDA) accumulation than normal cells after A/R injury. On the other hand, the TSPO- downregulated cells showed higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), mitochondrial function stabilization, resulting in less cell apoptosis and damage in case of A/R condition. In conclusion, TSPO expression is up-regulated under A/R injury, whereas repression of TSPO improves the endurance of cardiomyocytes against A/R injury by reducing oxidative stress, mitochondrial damage and cell apoptosis.

2.
J Cell Biochem ; 121(1): 651-660, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31407409

RESUMO

Idiopathic pulmonary fibrosis (IPF), a chronic, progressive and irreversible disease, needs long-term treatment. Bicyclol was found to play a great role in pulmonary fibrosis, and the present study is to explore how bicyclol affects IPF with the involvement of microRNA-455-3p (miR-455-3p) and Bax. Bleomycin (BLM) was used to induce the IPF model in Sprague-Dawley rats to detect the expression of miR-455-3p, Bax, and B-cell lymphoma factor 2 (Bcl-2). Moreover, to further investigate the mechanisms of bicyclol, the BLM-induced fibrotic cell model was used after the lung epithelial cells HPAEpiC received miR-455-3p knockout treatment. The rats were then treated with vehicle and bicyclol, respectively. The apoptosis of fibrotic cells and Bax/Bcl-2 were identified. Inhibition function of bicyclol was optimal at a dose of 150 mg/kg. Bicyclol inhibited cell apoptosis and reduced Bax/Bcl-2 expression in rats. miR-455-3p could potentially bind to Bax gene. Bicyclol reduced the levels of methylenedioxyamphetamine, superoxide dismutase, and glutathione in rat lung tissue, inhibited the apoptosis of rats with IPF and upregulated miR-455-3p expression. In vitro studies showed that bicyclol significantly promoted miR-455-3p expression in HPAEpiC fibrosis. Bicyclol inhibited fibrosis-induced apoptosis of HPAEpiC in alveolar epithelial cells through promoting miR-455-3p, which inhibited Bax expression in IPF. Bicyclol may suppress the apoptosis of alveolar epithelial cells by upregulating miR-455-3p. This study laid a theoretical foundation for further understanding of IPF and searching for new molecular therapeutic targets.

3.
Sci Total Environ ; 700: 134359, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31693952

RESUMO

Ammonia (NH3) emitted from motor vehicles is a by-product of measures taken to reduce emissions of other pollutants (e.g. NOx and CO) and has potentially important environmental impacts. NH3 levels can be impacted by various emission standards. However, there is a lack of investigations of the influences from the implementation of different vehicular emission standards on long-term changes in NH3 emissions. To fill this gap, we estimated the inter-annual NH3 emissions of light-duty gasoline vehicles (LDGVs) under different emission standards (State 0 to State V) from 1999 to 2017 and investigated the emission change characteristics under the rapidly developing Chinese economy. Results showed that the NH3 emissions from LDGVs had a sharp, 42-fold increase (from 1.8Gg to 77.9Gg). However, NH3 emissions per capita have begun to decrease with increases in socioeconomic development, presenting an inverted U-shaped tendency as a function of per capita GDP. Further exploration indicated that the decline in emission factors, as determined by upgrades in emission standards, was the decisive factor in promoting the downward trend in per capita emissions. This suggests that continuously upgrading emission standards has offset the increase in NH3 emissions due to the rapid growth of motor vehicles. Quantitative scenario analysis showed a two-stage impact of emission standards on NH3 emissions: emissions would decrease 77% (48%-90% for different years) if State I and State II were not implemented; while if none of standards were upgraded (State III to State V), NH3 emissions would increase 118% (13%-224% for different years), 2-6 times the impacts from the growth of vehicle population and the decline of vehicle kilometres traveled. The data and findings in this study can provide scientific support for understanding air pollution in urban areas and for formulating further vehicle pollution mitigation measures in China and other countries.

4.
J Environ Sci (China) ; 87: 39-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791512

RESUMO

Carbon-silica materials with hierarchical pores consisting of micropores and mesopores were prepared by introducing nanocarbon microspheres derived from biomass sugar into silica gel channels in a hydrothermal environment. The physicochemical properties of the materials were characterized by nitrogen physical adsorption (BET), scanning electron microscopy (SEM), and thermogravimetric (TG), and the adsorption properties of various organic waste gases were investigated. The results showed that microporous carbon materials were introduced successfully into the silica gel channels, thus showing the high adsorption capacity of activated carbon in high humidity organic waste gas, and the high stability and mechanical strength of the silica gel. The dynamic adsorption behavior confirmed that the carbon-silica material had excellent adsorption capacity for different volatile organic compounds (VOCs). Furthermore, the carbon-silica material exhibited excellent desorption characteristics: adsorbed toluene was completely desorbed at 150°C, thereby showing superior regeneration characteristics. Both features were attributed to the formation of hierarchical pores.

5.
Biosens Bioelectron ; 147: 111735, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634803

RESUMO

Design of suitable nanocomposites with tailored structures was significant in the fabrication of effective and reliable electrochemical sensors. Herein, the copper-nickel@nitrogen, boron-doped reduced graphene oxide (Cu-Ni@N,B-rGO) was successfully synthesized, which exhibited superior electrocatalytic performance towards guanine (G) and adenine (A) oxidation. The Cu-Ni NPs were sequentially decorated on N,B-rGO substrate via an environmentally friendly reduction strategy, which utilized glucose as reducer and stabilizing agent. The nanocomposites with large specific surface area, remarkable conductivity and high catalytic activity showed prominent synergistic effect owning to the uniform dispersion of Cu-Ni NPs on the surface of N,B-rGO. When applied to analysis of G and A using DPV, the wide linear ranges of 1.0-160.0 µM and 1.0-120.0 µM with the determination limits of 0.118 µM and 0.134 µM were obtained, respectively. The sensor was successfully applied to the detection of G and A in calf-thymus DNA with G/A ratio of 0.80. The facile preparation process and attractive sensing properties of the Cu-Ni@N,B-rGO nanocomposites made it a promising candidate for the development of advanced electrochemical sensor.

6.
J Cell Physiol ; 235(2): 1197-1208, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31270811

RESUMO

Chemotherapy is the first-line treatment option for patients with lung cancer. However, therapeutic resistance occurs through an incompletely understood mechanism. Our research wants to investigate the influence of Caveolin-1 (Cav-1) on the therapeutic sensitivity of lung cancer in vitro. Results in this study demonstrated that Cav-1 levels were markedly inhibited in A549 lung cancer cells after exposure to cisplatin. Knockdown of caveolin further enhanced cisplatin-triggered cancer death in A549 cells. The functional investigation demonstrated that Cav-1 inhibition amplified the mitochondrial stress signaling induced by cisplatin, as evidenced by the mitochondrial reactive oxygen species burst, cellular metabolic disruption, mitochondrial membrane potential reduction, and mitochondrial caspase-9-related apoptosis activation. At the molecular level, cav-1 augmented cisplatin-mediated mitochondrial damage by inhibiting Parkin-related mitochondrial autophagy. Mitophagy activation effectively attenuated the promotive impact of Cav-1 knockdown on mitochondrial damage and cell death. Furthermore, our data indicated that Cav-1 affected Parkin-related mitophagy by activating the Rho-associated coiled-coil kinase 1 (ROCK1) pathway; inhibition of the ROCK1 axis prevented cav-1 knockdown-mediated cell death and mitochondrial damage. Taken together, our results provide ample data illuminate the necessary action exerted by Cav-1 on affecting cisplatin-related therapeutic resistance. Silencing of Cav-1 inhibited Parkin-related mitophagy, thus amplifying cisplatin-mediated mitochondrial apoptotic signaling. This finding identifies the Cav-1/ROCK1/Parkin/mitophagy axis as a potential target to overcome cisplatin-related resistance in lung cancer cells.

7.
Sci Total Environ ; : 134636, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31791755

RESUMO

A large amount of NOX and SO2 emitted from ships may elevate atmospheric N and S and eventually aggravate the deposition of N and S. The understanding of N and S deposition due to ship emissions is still limited, especially for China because it has a long coastline, busy shipping routes, and several large ports. To fill this gap, a comprehensive air quality model was employed in this study to quantify the contributions of ship emissions to N and S deposition on a national scale in China. Both the spatial and temporal variations of N and S deposition, as well as the major N and S species from ship traffic, were investigated. The results indicate that ship emissions contributed significantly to the deposition of N and S, especially in coastal and offshore areas, where the largest ship contribution to both N and S deposition could exceed 15 kg·ha-1·yr-1. For N deposition, ship emissions caused an increase in the total N deposition, not only in port areas and along shipping routes but also far inland, with evident seasonal variations. The contribution from dry N deposition was evidently larger than wet N deposition, especially over the coastal areas. S deposition, however, was generally higher along shipping routes but exhibited distinct seasonal variations. The total S deposition was dominated by dry deposition, especially over offshore areas. Ship-caused dry S deposition occurred mainly in offshore areas, while wet S deposition could be found over wider inland regions and inland waterways, although with a markedly smaller magnitude.

8.
Biomolecules ; 9(12)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801241

RESUMO

When insects attack plants, insect-derived elicitors and mechanical damage induce the formation and emission of plant volatiles that have important ecological functions and flavor properties. These events have mainly been studied in model plants, rather than crop plants. Our study showed that tea green leafhopper (Empoasca (Matsumurasca) onukii Matsuda), a major pest infesting tea attack significantly induced the emission of geraniol from tea leaves, but did not affect the crude enzyme activity of geraniol synthase in tea leaves. An enzyme extract of E. (M.) onukii specifically produced geraniol from geraniol diphosphate. Furthermore, a terpene synthase (EoTPS) was isolated from E. (M.) onukii. This terpene synthase was able to convert geraniol diphosphate to geraniol in vitro. In addition, geraniol had in vitro ability to inhibit the growth of Acinetobacter johnsonii that is endobacterial isolated from E. (M.) onukii. This information illustrates that elicitors from piercing-sucking insects can induce the formation of volatiles from crop plants and advances our understanding of the roles of plant volatiles in the interaction among crops-insects-microorganisms.

9.
Cell Death Dis ; 10(12): 918, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801938

RESUMO

Resident macrophages in the tumor microenvironment exert a dual role in tumor progression. So far, the mechanism of intratumoral macrophage generation is still largely unknown. In the present study, the importance of macrophages in the pro-tumor role of gastric cancer-derived mesenchymal stromal cells (GC-MSCs) was observed in a mouse xenograft model with macrophage depletion. In gastric cancer tissues, high expression levels of Ym-1, Fizz-1, arginase-1, and CCR-2, as well as a low expression level of iNOS, were verified, and co-localization of GC-MSCs and tumor-associated macrophages (TAMs) was observed by dual immunofluorescence histochemistry. TAMs isolated from gastric cancer tissues predominantly displayed an M2 phenotype. In a co-culture system, the contribution of GC-MSCs to M2 polarization of macrophages was confirmed by the M2-related protein expression, M2-like immunophenotype and cytokine profile of GC-MSC-primed macrophages in vitro. Blockade of IL-6/IL-8 by neutralizing antibodies significantly attenuated the promoting effect of GC-MSCs on M2-like macrophage polarization via the JAK2/STAT3 signaling pathway. In addition, GC-MSC-primed macrophages promoted the migration and invasion of gastric cancer cells, and the process of EMT in gastric cancer cells was significantly enhanced by GC-MSC-primed macrophage treatment. Our study showed that tumor-promoting GC-MSCs contribute to M2 macrophage polarization within the gastric cancer niche through considerable secretion of IL-6 and IL-8. These GC-MSC-primed macrophages can subsequently prompt gastric cancer metastasis via EMT promotion in gastric cancer cells.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31802653

RESUMO

The oxygen vacancy-containing semiconductor photocatalysts have been extensively studied and applied in environmental and energy fields, but there are a few studies concerning the mechanisms of inactivation and regeneration of oxygen vacancies to prevent the catalysts from deactivation. In this paper, we put forward a novel in situ method to introduce the oxygen vacancies into BiSbO4 (BiSbO4-OV) via UV-light induced breaking down of Bi-O and Sb-O bonds. The formation of oxygen vacancies could broaden the photo-response range and improve the charge carries separation as confirmed by DFT calculation, UV and PL spectra. The unique electronic structure of oxygen vacancies enabled the BiSbO4 with high visible light photocatalytic NO activity. It was significant to reveal that oxygen in the air could fill the oxygen vacancy sites during the photocatalytic reaction, and the consumption of the oxygen vacancies led to the direct deactivation of BiSbO4-OV. By re-irradiation of the deactivated photocatalysts, the BiSbO4-OV could get back to its initial state, realizing the refreshment of oxygen vacancies for sustainable photocatalysis. Additionally, the visible light photocatalytic NO conversion pathway on BiSbO4-OV was uncovered via in situ DRIFTS based on the identification of the reaction intermediates and products. The light induced generation and regeneration of oxygen vacancies could also be extended in other semiconductors for sustainable visible light photocatalysis.

11.
Curr Drug Metab ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755383

RESUMO

BACKGROUND: Cardiovascular disease has one of the highest mortality rates among all the diseases. Platelets play an important role in the pathogenesis of cardiovascular diseases. Platelet membrane glycoprotein GPIIb/IIIa antagonists are the most effective antiplatelet drugs, and pulaimab is one of these. The study aims to promote individual medication of pulaimab [anti-GPIIb/IIIa F(ab)2 injection] by discovering the pharmacological relationship among the dose, concentration, and effects. The goal of this study is to establish a population pharmacokinetic-pharmacodynamic model to evaluate the antiplatelet effect of intravenous pulaimab injection. METHODS: Data were collected from 59 healthy subjects who participated in a Phase-I clinical trial. Plasma concentration was used as the pharmacokinetic index, and platelet aggregation inhibition rate was used as the pharmacodynamic index. The basic pharmacokinetics model was a two-compartment model, whereas the basic pharmacodynamics model was a sigmoid-EMAX model with a direct effect. The covariable model was established by a stepwise method. The final model was verified by a goodness-of-fit method, and predictive performance was assessed by a Bootstrap (BS) method. RESULTS: In the final model, typical population values of the parameters were as follows: central distribution Volume (V1), 183 L; peripheral distribution Volume (V2), 349 L; Central Clearance (CL), 31 L/h; peripheral clearance(Q), 204 L/h; effect compartment concentration reaching half of the maximum effect (EC50), 0.252 mg/L; maximum effect value (EMAX), 54.0%; and shape factor (γ), 0.42. In the covariable model, thrombin time had significant effects on CL and EMAX. The verification by the goodness-of-fit and BS methods showed that the final model was stable and reliable. CONCLUSION: A model was successfully established to evaluate the antiplatelet effect of intravenous pulaimab injection that could provide support for the clinical therapeutic regimen.

12.
Stem Cells ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31721356

RESUMO

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo. Krüppel-like Factor 2 (KLF2) is an important indicator of the stemness of hMSCs [1], and as early vascularization is also critical for bone regeneration, we used KLF2 as a novel in vitro marker for MSCs and investigated the angiogenesis and osteogenesis between KLF2+ MSCs and endothelial cells (ECs). We found a synergistic interaction between hMSCs and human umbilical vein ECs (HUVECs) in that KLF2+ stemness-maintained hMSCs initially promoted the angiogenesis of HUVECs, which in turn more efficiently stimulated the osteogenesis of hMSCs. In fact, KLF2+ hMSCs secreted angiogenic factors initially, with some of the cells then differentiating into pericytes through the PDGF-BB/PDGFR-ß signaling pathway, which improved blood-vessel formation. The matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through upregulated vascular endothelial growth factor (VEGF). A three-dimensional (3D) coculture model using cell-laden GelMA hydrogel further confirmed these results. This study provides insight into the stemness-directed synergistic interaction between hMSCs and HUVECs, and our results will have a profound impact on further strategies involving the application of KLF2+ hMSC/HUVEC-laden GelMA hydrogel in vascular network bioengineering and bone regeneration. © AlphaMed Press 2019 SIGNIFICANCE STATEMENT: KLF2 was creatively put forward as a novel marker in vitro for MSCs to investigate the osteogenesis and angiogenesis between KLF2+ MSCs and ECs. We demonstrated there was a synergistic strategy to help readers understand the process of intercellular interaction between hMSCs and HUVECs, which KLF2+ hMSCs secreted angiogenic factors like ANG1 initially, and some of hMSCs then differentiated into pericytes through PDGF-BB/PDGFR-ß signaling pathway. Both of which improved the formation of blood vessels. Matured HUVECs in turn synergistically enhanced the osteogenesis of KLF2+ hMSCs through the up-regulated VEGF more efficiently. This work therefore focuses on the synergistic strategy between KLF2+ hMSCs and HUVECs and will have a profound impact on further vascular network bioengineering and bone regeneration.

13.
Res Social Adm Pharm ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31668903

RESUMO

According to the World Health Organization (WHO), more than 36 million people die annually from non-communicable diseases (NCDs), representing over 60% of deaths worldwide, 15 million of which occur before the age of 70 years. Prevention and control of NCDs and their risk factors require interventions that are therapeutically cost-effective, affordable by the patient and/or health systems and feasible, based upon local resources. This commentary paper sets a basis of global evidence to advocate, nationally and internationally, for an expanded role for pharmacists in NCD management by compiling best practices and examples. It encourages pharmacists around the world to act upon NCDs, from prevention and screening activities, to patient referral when appropriate, and to pharmacist-led, patient-centred NCD management to improve outcomes and quality of life. Priority NCDs fall into four areas: cardiovascular diseases, diabetes, asthma/chronic obstructive pulmonary disease and cancer. Building on the key roles they already play as primary healthcare professionals in the community, pharmacists can provide focused interventions, specialised counselling and care coordination, improving patient engagement to achieve better outcomes in the global fight against NCDs.

14.
Org Biomol Chem ; 17(44): 9567-9572, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686070

RESUMO

Inspired by the chemistry and biology of chromone and oxindole derivatives, herein we report the first example of thermal-mediated [1,3]-hydrogen transfer as the key step for the efficient synthesis of oxindole-chromone hybrid collections 2, which avoids additional catalyst and solvent conditions. All the oxindole-chromones 2 are smoothly obtained in >99% yields in all cases, avoiding column chromatography purification. In particular, the products 2 can act as potential synthons for further elaboration in structural diversity, which might be valuable in organic and medicinal chemistry.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1094-1096, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703133

RESUMO

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of fetal chromosomal aneuploidies. METHODS: For 9470 pregnant women with a moderate-to-high risk by conventional serological screening or advanced maternal age, peripheral venous blood samples were collected and, following extraction of free fetal DNA, subjected to large-scale parallel sequencing on a Illumina Hiseq2000 platform. Those with a high risk by NIPT were validated by invasive prenatal diagnosis. RESULTS: Out of the 9470 samples, 194 cases (2.0%) were positive by NIPT testing. These included 50 trisomy 21, 11 trisomy 18, 17 trisomy 13, 44 other autosomal aneuploidies, 55 sex chromosomal aneuploidies, and 17 chromosomal copy number variations. As validated by amniotic fluid or umbilical blood chromosomal karyotyping analysis, NIPT has a false positive rate of 2.0%, 18.2%, 41.2%, 97.7%, 81.8%, 94.1%, respectively. The test has a sensitivity of 100% and a specificity of 98.79%. CONCLUSION: For common chromosomal aneuploidies such as trisomy 21 and trisomy 18, NIPT has a good sensitivity and specificity, therefore has good value for clinical application.


Assuntos
Aneuploidia , Transtornos Cromossômicos/diagnóstico , Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Feminino , Humanos , Gravidez , Sensibilidade e Especificidade , Trissomia , Síndrome da Trissomía do Cromossomo 18
16.
BMC Med Imaging ; 19(1): 87, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718581

RESUMO

BACKGROUND: Solid-pseudo papillary neoplasms of pancreas (SPNP) are rare in men and are often misdiagnosed. This study aimed to analyze the clinical and multi-slice computer tomography (MSCT) features of patients with SPNP, and examine the differences between males and females. METHODS: In this retrospective cohort study, the clinical and imaging data of 29 patients with histolopathologically confirmed SPNP (seven males and 22 females) that underwent radical resection, and underwent preoperative MSCT at the First People's Hospital of Lianyungang between August 2010 and December 2018 were collected. All MSCT images were reviewed by two radiologists; disagreements were ruled by a third one. RESULTS: The median age of the 29 patients with SPNP was 30 (range, 12-70) years. The male patients were older than the female patients [median, 56 (28-66) vs. 29 (12-70), P = 0.012]. The median tumor size was 3.9 (range, 2.0-6.4) cm in the male SPNP patients, which was significantly lower than the 7.0 (range, 4.6-14.6) cm in the female patients (P < 0.001). The calcification rate of the SPNP was significantly higher in male than in female patients (P = 0.013). The percentage of solid tumor was higher in males than in females (P = 0.036). Capsule, bleeding, and enhancement in the arterial and venous phases were not significantly different between the male and female patients (all P > 0.05). CONCLUSION: The imaging features of male SPNP are distinct from those of female patients. In males with pancreatic lesions, MSCT generally shows relatively small lesions with higher percentages of solid components and calcification, with typical enhancement suggesting SPNP.

17.
J Immunol Res ; 2019: 7024905, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737687

RESUMO

Objective: Asthma is a syndrome that incorporates many immune phenotypes. The immunologic effects of subcutaneous immunotherapy (SCIT) exerts on allergic asthma remain still largely unknown. Here, we investigated the effects of SCIT on cytokine production and peripheral blood levels of lymphocyte subtypes in children with mite-induced moderate and severe allergic asthma. Methods: The study included 60 kids with mite-induced allergic asthma from 5 to 10 years old. All subjects had received antiasthmatic pharmacologic for 3 months at baseline. Half of the children were treated with SCIT combined with pharmacologic treatment named the SCIT group and the other half only with pharmacologic therapy named the no-SCIT group. Total asthma symptom score (TASS) and total medication score (TMS) were recorded. Flow cytometry was used to identify lymphocyte subtypes: type 2 innate lymphocytes (ILC2s), type 1 (Th1) and type 2 (Th2) helper T cells, T helper 17 (Th17) cells, and regulatory T (Treg) cells. ELISA, flow cytometry, and cytometric bead array were used to assess cytokines IL-13, IFN-γ, IL-4, IL-17, and TGF-ß, at baseline and 3 and 6 months after study treatment in both groups of patients. Results: Both groups can significantly improve clinical symptoms in children with asthma. SCIT can significantly reduce asthma medication after 6 months of treatment. SCIT induced a significantly higher and progressive reduction in ILC2 percentage and IL-13 levels after 3 and 6 months of treatment compared with baseline and compared with no-SCIT patients. Significant differences were detected in the Th1/Th2 cell ratio and IFN-γ/IL-4 cytokine ratio between groups after 6 months of treatment. Similarly, the Th17/Treg ratio and IL-17/TGF-ß ratio in the SCIT group were much lower than those in the no-SCIT group after 3-6 months of treatment. Conclusion: SCIT is a promising option to reduce the percentage of ILC2 and regulate Th1/Th2 and Th17/Treg immune balance in the peripheral blood of children with asthma.

18.
Int Ophthalmol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758506

RESUMO

PURPOSE: To evaluate medium-term clinical outcomes with microstent XEN® 45 Gel Stent (Allergan Dublin, Ireland) for treatment of primary open-angle glaucoma (POAG). MATERIAL AND METHODS: This is a retrospective, descriptive and observational study involving 93 eyes from 63 patients who had undergone POAG surgery with a XEN® 45 Gel Stent implantation and had been followed up and controlled between 12 and 36 months. RESULTS: IOP dropped from 18.23 ± 5.00 mmHg pre-op to 14.16 ± 2.14, 14.47 ± 2.16 and 14.63 ± 1.91 at 1, 2 and 3 years after surgery (p = 0.000, 0.000 and 0.001) consecutively. Mean number of medications dropped from 1.87 ± 0.94 preoperatively to 0.31 ± 0.69, 0.34 ± 0.63 and 1.00 ± 0.88 (p = 0.000, 0.000 and 0.017) at 12, 24 and 36 months. Mean visual field deviation values never turned out to be significant for any of the follow-up visit data. A total of 94.6% of the surgical procedures turned out to be complication-free. In one surgery, the procedure failed and 18 months later other device was implanted. CONCLUSION: POAG surgical procedures with XEN® 45 Gel Stent implants are a safe and effective treatment approach.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31758718

RESUMO

BACKGROUND AND AIM: In this largest pediatric cohort to date in Asian population, we aimed to report our long-term real-life experience with thalidomide treatment in pediatric Crohn's disease (CD). METHODS: A retrospective single-center analysis of pediatric CD patients treated by thalidomide was conducted. The clinical characteristics and outcomes were extracted. Primary outcomes were clinical response and remission rate at different time points, especially comparing the difference between monogenic and non-monogenic mutation patients. We also evaluated the long-term safety of thalidomide. RESULTS: A total of 62 patients met the inclusion criteria. The median follow-up period was 30.5 months. Among all, 19 patients (30.6%) were diagnosed with monogenic mutation during treatment. Clinical remission rate was 53.2% (33/62) at 6 months, 54.8% (34/62) at 12 months and 33.9% (21/62) at the end of follow-up, respectively. Clinical remission rates between monogenic and non-monogenic groups at the end were statistically different (44.2%(19/43) vs. 10.5%(2/19), P < 0.05). At 12 months, 66.7% (30/45) were with normalized C-reactive protein level. Most patients (95.4%, 21/22) discontinued steroids with a median time of 4.4 months. Twelve patients relapsed, but no risk factor was identified to be significantly associated with relapse. A total of 45.2% (28/62) patients experienced an adverse event, in which 22 patients stopped thalidomide due to safety concern. Cumulative dose was not associated with abnormal electromyography, but with the occurrence of adverse events. CONCLUSIONS: Thalidomide was clinically efficacious and safe among pediatric CD. Our results suggest it is an alternative therapy in monogenic mutation patients.

20.
Analyst ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724655

RESUMO

Single nucleotide polymorphisms (SNPs) have been proven to be important biomarkers for disease diagnosis, prognosis and disease pathogenesis. Here, taking the advantages of a self-assembled oligonucleotide sandwich structure and robust chemical reactions, we have developed a simple, high-throughput and effective colorimetric analytical technique termed CuAAC-based ligation-assisted assays (CuAAC-LA) for SNP detection using a DNA-BIND 96-well plate. With the 5'-azide and 3'-alkyne groups labelled on two oligonucleotide probes, the target DNA can direct a Cu(i)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction. Since the small difference in duplex stability caused by a single-nucleotide mismatch was amplified by the steric effects of these reactive groups for the ligation reaction of an unstable duplex, CuAAC-LA exhibited an ultra-sensitive discrimination ability for a mutant type target in the presence of large amounts of wild type targets. As low as 0.05% SNP could be clearly detected, which was better than most previously reported methods by various DNA ligases, indicating that a simple and rapid synthetic method i.e., the DNA template-directed click reaction held the potential to replace the ligase for SNP detection.

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