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1.
《药学学报(英文版)》2020,10(10):1926-1942
Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses. 相似文献
2.
目的比较Ⅱ型排卵障碍女性使用克罗米芬(CC)方案或来曲唑(LE)方案诱导排卵后供精人工授精(AID)周期的临床结局和妊娠结局。方法回顾性分析2012年1月至2019年8月578名Ⅱ型排卵障碍妇女在我中心完成的1253个AID周期的超声监测数据及临床资料。比较单用CC或LE或联合促性腺激素(Gn)诱导排卵的AID周期的参数和临床结局。采用单因素和多因素Logistic回归分析,探讨诱导排卵方案与宫内妊娠和活产的关系。比较CC及LE方案的妊娠结局和新生儿出生状况。结果总体上4种方案的宫内妊娠率和活产率无显著差异(P>0.05);校正混杂因素后,与单用CC相比,CC联合Gn及LE联合Gn均显著促进宫内妊娠(分别为OR=1.641,P=0.024;OR=1.543,P=0.019)和活产(分别为OR=1.589,P=0.047;OR=1.508,P=0.034),而单用LE与单用CC相比均无显著差异(P>0.05);各种妊娠结局的发生率及新生儿出生状况在CC及LE方案之间均无显著差异(P>0.05)。结论在宫内妊娠和活产方面,无论单用还是与Gn联用,LE与CC疗效相当,且联用Gn优于单用;LE和CC方案的妊娠结局及新生儿出生状况基本可比。 相似文献
3.
4.
目的探讨不同时机应用枸橼酸咖啡因对早产儿结局及神经发育的影响。方法选取2018年1月至6月于我院新生儿重症监护室住院治疗的胎龄小于32周、体重小于1500 g的早产儿共113例为研究对象,按开始使用枸橼酸咖啡因的日龄分为早期治疗组(日龄≤1 d,53例)和晚期治疗组(1 d<日龄≤10 d,60例),回顾性收集并比较两组患儿围生期的基本情况、治疗过程、临床结局,并针对神经发育情况随访至12月龄。结果早期治疗组患儿支气管肺发育不良、动脉导管未闭及脑室内出血/脑室周围白质软化的发生率低于晚期治疗组,差异均有统计学意义(均P<0.05)。早期治疗组纠正胎龄40周时新生儿神经行为测定评分高于晚期治疗组,差异有统计学意义(P<0.05)。早期治疗组纠正胎龄3月龄时智力发育指数高于晚期治疗组,纠正胎龄至12月龄时智力发育指数及运动发育指数均高于晚期治疗组,差异均有统计学意义(均P<0.05)。结论早期应用枸橼酸咖啡因可改善早产儿结局,改善神经系统预后。 相似文献
5.
Dominique Trudel Luminita-Mihaela Avarvarei Michèle Orain Stéphane Turcotte Marie Plante Jean Grégoire Reinhild Kappelhoff David P. Labbé Dimcho Bachvarov Bernard Têtu Christopher M. Overall Isabelle Bairati 《Pathology, research and practice》2019,215(6):152369
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
6.
Somchai Sawatdee Apichart Atipairin Attawadee Sae Yoon Teerapol Srichana Narumon Changsan 《Pharmaceutical development and technology》2019,24(1):1-11
Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5?kg, friability test <1% with a disintegration time <5?min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months. 相似文献
7.
王昌燕 《中国儿童保健杂志》2019,27(4):421-424
目的 比较枸橼酸咖啡因和氨茶碱对早产儿神经行为发育的影响,为早产儿早期合理干预提供临床依据。方法 选择2014年6月-2018年6月在中国西电集团医院新生儿科住院接受枸橼酸咖啡因治疗的原发性呼吸暂停(AOP)早产儿62例作为研究组;2011 年 12 月-2014年5月同在中国西电集团医院新生儿科住院采用氨茶碱治疗的AOP患儿69例作为对照组。出生3~8 d及矫正胎龄40周时分别行头颅MRI检查,评估脑白质损伤(WMD)并进行两组比较;6个月及12个月时应用Gesell婴幼儿发育量表测试比较两组神经行为发育水平。结果 两组患儿在性别、出生胎龄及体重、产前孕母糖皮质激素应用及分娩方式、5 min Apgar评分、辅助通气和表面活性物质的应用等方面差异均无统计学意义(P>0.05)。首次头颅MRI显示两组患儿WMD差异无统计学意义(P>0.05)。矫正胎龄40周时头颅MRI显示,咖啡因组WMD较氨茶碱组明显改善,差异有统计学意义(P<0.05);且6个月及12个月时Gessell婴幼儿发育量表测试,随访至校正6月龄时,咖啡因组患儿的大运动、精细运动及个人-社交评分均高于氨茶碱组(P<0.05);随访至校正12月龄时,咖啡因组患儿的大运动、精细运动、语言、适应性评分均高于氨茶碱组(P<0.05)。结论 枸橼酸咖啡可明显改善AOP患儿6个月及12个月时的神经行为发育。 相似文献
8.
Eric Therasse Véronique Caty Patrick Gilbert Marie-France Giroux Pierre Perreault Louis Bouchard Vincent L. Oliva Jacques Lespérance Jean Ethier Georges Ouellet Martin Francoeur Serge Cournoyer Gilles Soulez 《Journal of vascular and interventional radiology : JVIR》2021,32(3):350-359.e2
PurposeTo assess whether angioplasty of hemodialysis access (HA) stenosis with a drug-coated balloon (DCB) would prevent restenosis in comparison with plain-balloon percutaneous transluminal angioplasty (PTA).Materials and MethodsThis prospective randomized clinical trial enrolled 120 patients with dysfunctional arteriovenous fistulae (n = 109) and grafts (n = 11), due to a ≥50% stenosis between March 2014 and April 2018. All patients underwent high-pressure balloon angioplasty and were then randomized to either DCB (n = 60) or PTA (n = 60). Patients were followed-up for 1 year, and angiography was performed 6 months after angioplasty. The primary endpoint was the late lumen loss (LLL) at 6 months. Secondary endpoints included other angiographic parameters at 6 months and HA failures, adverse event, and mortality at 12 months. Continuous variables were compared with a Student t-test, and Kaplan-Meier curves were used for freedom from HA failure and for mortality.ResultsLLL in the DCB and in the PTA group were 0.64 mm ± 1.20 and 1.13 mm ± 1.51, respectively (P = .082, adjusted P = .0498). DCB was associated with lower percentage stenosis (54.2% ± 19.3 vs 61.7% ± 18.2; P = .047) and binary restenosis ≥50% (56.5% vs 81.1%; P = .009) than PTA. The number of HA failures after 12 months was lower for DCB than for PTA (45% vs 66.7%; P = .017). Mortality at 12 months was 10% and 8.3% in the DCB and PTA groups, respectively (P = .75).ConclusionsDespite LLL improvement that failed to reach statistical significance, this study demonstrated decreased incidence and severity of restenosis with DCB compared with PTA to treat dysfunctional HA. 相似文献
9.
A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product. 相似文献
10.
Sedigheh Kianpour Alireza Ebrahiminezhad Maryam Deyhimi Manica Negahdaripour Mohammad Javad Raee Milad Mohkam Hamideh Rezaee Cambyz Irajie Aydin Berenjian Younes Ghasemi 《Journal of basic microbiology》2019,59(6):569-578
The biocompatible‐coated iron oxide nanoparticles (IONs) have attracted a great interest because of their various applications in biological science and medicine. In most cases, the toxic effect of naked iron oxide nanoparticles is completely cleared by adding a biocompatible coating, such as polysaccharides, polyethylene glycol (PEG), or biosynthesis of biocompatible‐coated IONs using microorganisms such as bacteria. In the present study, polysaccharide‐coated iron oxide nanoparticles were produced by a strain of Staphylococcus warneri isolated from a thermal spring. For identification of the isolated bacterium, 16S rRNA gene sequencing was done. Characterization of the nanoparticles was performed for the first time, using transmission electron microscopy (TEM), dynamic light scattering (DLS), thermogravimetric analysis (TGA), X‐ray crystallography (XRD), Fourier‐transform infrared (FTIR) spectroscopy, vibrating sample magnetometer (VSM), and 3‐(4,5‐dimethylthiazol‐2‐yl)?2,5‐diphenyltetrazolium bromide (MTT) assay. Results indicated that the spherical iron oxide nanoparticles were coated by a polysaccharide (13.6%), which provided a large negative charge of ?91 mV and very low saturation magnetization of around 0.28 emu/g. The result of MTT assay on MOLT‐4 cell lines showed that the percentage of viability was between 95.6% and 68.9% in the 10–100 µM of nanoparticle concentrations with a high IC 50 value, which makes it appropriate for biomedical applications such as cancer therapy. 相似文献