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1.
PLoS One ; 16(11): e0259732, 2021.
Article in English | MEDLINE | ID: mdl-34780505

ABSTRACT

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.


Subject(s)
Acute Lung Injury/complications , Acute Lung Injury/virology , COVID-19/pathology , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , Pneumonia/complications , Pneumonia/virology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Disease Models, Animal , Extracellular Vesicles/ultrastructure , Humans , Immunomodulation , Male , Models, Biological , Pneumonia/pathology , Rats, Sprague-Dawley , SARS-CoV-2/physiology , Signal Transduction , THP-1 Cells
2.
J Pharmacol Exp Ther ; 368(1): 116-124, 2019 01.
Article in English | MEDLINE | ID: mdl-30377215

ABSTRACT

The gastrointestinal (GI) prokinetic effects of ghrelin occur through direct peripheral effects on ghrelin receptors within the enteric nervous system and via the ghrelin receptor on the vagus nerve, which activate a centrally mediated mechanism. However, the relative contribution of peripheral versus central effects to the overall prokinetic effect of ghrelin agonists requires further investigation. Here, we investigated the central versus peripheral prokinetic effect of ghrelin by using two novel ghrelin agonists: HM01 (N'-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-N-methyl-N-[1,3,3-trimethyl-(4R)-piperidyl]-urea HCL) with high brain penetration compared with HM02 (N'-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-N-hydroxy-N-(1-methyl-4-piperidinyl)-urea), a more peripherally acting ghrelin agonist. The pharmacokinetic profiles of both ghrelin agonists were evaluated after intravenous and oral administration in rats. The efficacy of HM01 and HM02 was assessed in a rat model of postoperative ileus (POI) induced by abdominal surgery and in a rodent defecation assay. Pharmacokinetic results in our models confirmed that HM01, but not HM02, was a brain-penetrant ghrelin agonist. Administration of either HM01 or HM02 reversed the delayed upper and lower gastrointestinal transit induced by abdominal surgery to levels resembling the non-POI controls. In the defecation test, HM01, but not HM02, significantly increased the weight of fecal pellets. Our findings suggest that, in a rodent model of POI, synthetic ghrelin agonists stimulate GI transit through a peripheral site of action. However, in the defecation assay, our data suggest that a ghrelin-mediated mechanism is located at a central site. Taken together, a ghrelin agonist with both central and peripheral prokinetic activity may show therapeutic potential to treat delayed GI transit disorders.


Subject(s)
Biomimetic Materials/administration & dosage , Gastrointestinal Transit/physiology , Ghrelin/administration & dosage , Ghrelin/agonists , Piperidines/administration & dosage , Administration, Intravenous , Administration, Oral , Animals , Dose-Response Relationship, Drug , Gastrointestinal Motility/drug effects , Gastrointestinal Motility/physiology , Gastrointestinal Transit/drug effects , Male , Rats , Rats, Sprague-Dawley
3.
Journal of Modern Laboratory Medicine ; (4): 143-144,147, 2017.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-610894

ABSTRACT

Objective To evaluate the comparability of the test results of two immunoassay systems based on the electrochemical luminescence and the fluorescence lateral flow immunoassay for serum procalcitonin (PCT).Methods Roche cobas system was used as the reference system,and fluorescence lateral flow immunoassay system of Shanghai Upper biotech company was used as evaluated system.A total of 141 clinical samples during November,2015 were detected by the two systems to obtain the correlation coefficient and the Kappa values at the two cutoff values(0.5,2.0 ng/ml).Results The two systems showed high correlation (Y=1.008X-0.032,r=0.995,P<0.001) and low deviation (t=-0.230,P=0.819>0.05) without statistic significance between two methods.Kappa values were 0.944,0.943 respectively at the two cutoff values (0.5,2.0 ng/ml).Conclusion The test results showed no significant difference between the two immunoassay systems,suggesting a consistency between them for clinical detection of PCT.All the observed indicators reached the clinical diagnostic requirements and the method of quantitative detection of PCT by fluorescence lateral flow immunoassya can be applied for the quick detection of clinical human PCT.

4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-621042

ABSTRACT

Objective To retrospectively analyse the detection results of human leukocyte antigen(HLA) B27,and discuss its diagnosis value in disease such as ankylosing spondylitis(AS).Methods HLA-B27 detection was performed on 1 335 suspected AS patients treated in the hospital from January 2015 to June 2016 by using multiparameter flow cytometry instrument.The test results showed 201 patients were diagnosed with AS(AS group),1 134 patients were diagnosed with rheumatoid arthritis and other related diseases (non AS group).The test results were shown by using mean fluorescence intensity and positive lymphocyte expression rate.n addition,120 healthy people were enrolled as the control group in the physical examination center of the hospital.Results The positive rate of HLA-B27 screening in suspected AS patients was 15.73% (210/1 335),and the positive rate of HLA-B27 screening in the control group was 2.50% (3/120).The positive rate of HLA-B27 screening,the rate of cell expression and the average fluorescence intensity of AS group were 92.03%(185/201),(85.34±17.99)%,8.74±4.20,significantly higher than the non AS group and the control group(P0.05).HLA-B27 screening positive patients were mainly concentrated in adolescence,and the positive rate of male was higher than that of female (P<0.05).Conclusion Flow cytometry examination of HLA-B27 can provide important basis for the diagnosis and differential diagnosis of AS.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-505434

ABSTRACT

Writing and publishing scientific papers is a very important part of the research work.The quality of the thesis is also an important indicator to measure the achievements of scientific research workers.The quality of the thesis mainly includes the academic quality and the writing quality,but some of the researchers are mostly proficient in practice and neglect the writing,so there are still many writing problems in the manuscript.By reading the submission specification,this article summarizes the common problems in the writing,so as to provide the reference value for the readers.

6.
China Medical Equipment ; (12): 14-16,17, 2015.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-602798

ABSTRACT

Objective:To solve the inaccurate results caused by the aging of nitrocellulose membranes in qualitative or quantitative immuno-colloidal gold infiltration tests.Methods: Using qualitative TB-DOT and quantitative HCG-DOT immuno-colloidal gold filtration test systems, we compared the treated coloration, circulation velocity, adsorbing power and stability of nitrocellulose membrane of good quality, 3-methyl-1-butanol treated and untreated aged membranes. Results: Abundant results has approved that the regeneration of aged nitrocellulose membrane by 3-methyl-1-butanol treatment lead to 14.4% faster flow velocity, stronger absorption capability, better stability, and lower CV value, compared to untreated membranes.Conclusion:The mentioned method solves the problem caused by the aging of nitrocellulose membranes, and assures the accuracy of measurements. Furthermore, it is an universal solution that can be applied to other POCT products.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-550639

ABSTRACT

Quercetin (0.05~0.20 mmol/L, final concentration) obviously inhibited the aggregation and production of PGE2 and TXB2 of human PMN which were induced by AA ( 0.66 mmol/L), LTB4 ( 0.002 mmol/L) and the fourth composition of cobra venom of Guangxi Province ( 4.8mg/L) in vitro. These effects were dose dependent, the IDg50 of PMN aggregation induced by AA, LTB4 and the fourth composition of cobra venom of Guangxi Province was 68?mol/L, 59?mol/L and 61?mol/L respectively. At the concentration of 0.50?mol/L, it can also inhibit lysozyme release of PMN induced by AA, LTB4 and the fourth composition of cobra venom of Guangxi Province.

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