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1.
Artigo em Inglês | MEDLINE | ID: mdl-33634551

RESUMO

Precise control of the composition and structure of active sites in an atom-by-atom fashion remains insuperable for heterogeneous catalysts. Here, we introduce the tailor-made catalytic sites for the cycloaddition of CO2 to epoxides achieved by implementing Ag atoms at different liberated levels in atomically precise Au nanoclusters. Our results reveal that a singly open Ag site on the Au19Ag4 cluster improves the ring-opening of epoxides and sequent CO2 insertion, while the partially exposed Ag site on the Au20Ag1 cluster exhibits a weak affinity for epoxides and poor efficiency of CO2 capture. Structural tunability imparted by atom-by-atom tailoring and unusual atomic charges distributed on Au and Ag atoms of the three clusters seem to be crucial for promoting challenging bond cleavages and formations in chemical utilization of CO2.

2.
Exp Neurol ; 339: 113642, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600816

RESUMO

Hematopoietic cell-specific protein 1 associated protein X-1 (HAX-1) is a novel mitochondrial protein that regulates oxidative stress-induced apoptosis. However, the roles of HAX-1 in ischemic neuronal injury have not been thoroughly elucidated. In this study, the expression and roles of HAX-1 after ischemic stress were investigated using in vivo and in vitro models. The effect of oxidative stress on the regulation of HAX-1 was examined using knockout mice lacking nicotinamide-adenine dinucleotide phosphate oxidase 2 (NOX2), which is a major source of reactive oxygen species (ROS) after cerebral ischemia. Male C57BL/6 J mice were subjected to transient forebrain ischemia induced by 22-min occlusion of the bilateral common carotid arteries, and striatum samples were analyzed. For in vitro ischemic experiments, oxygen and glucose deprivation (OGD) in a rat pheochromocytoma cell line was utilized. Western blotting and immunofluorescence analysis revealed HAX-1 expression in neuronal mitochondria, which was significantly decreased after ischemia in vivo and in vitro. In NOX2 knockout mice, ischemia-induced decrease in HAX-1 expression and ischemic neuronal injury was significantly alleviated compared to those in wild-type mice. Inhibition of HAX-1 using small interfering RNA significantly increased injury in cultured cells after OGD. These findings suggest that HAX-1 has a neuroprotective effect against ischemic neuronal injury, and downregulation of HAX-1 by NOX2-produced ROS induces apoptosis after cerebral ischemia.

3.
Environ Int ; 147: 106361, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33401173

RESUMO

Corona virus disease 2019 has spread worldwide, and appropriate drug design and screening activities are required to overcome the associated pandemic. Using computational simulation, blockade mechanism of SARS-CoV-2 spike receptor binding domain (S RBD) and human angiotensin converting enzyme 2 (hACE2) was clarified based on interactions between RBD and hesperidin. Interactions between anti-SARS-CoV-2 drugs and therapy were investigated based on the binding energy and druggability of the compounds, and they exhibited negative correlations; the compounds were classified into eight common types of structures with highest activity. An anti-SARS-CoV-2 drug screening strategy based on blocking S RBD/hACE2 binding was established according to the first key change (interactions between hesperidin and S RBD/hACE2) vs the second key change (interactions between anti-SARS-CoV-2 drugs and RBD/hACE2) trends. Our findings provide valuable information on the mechanism of RBD/hACE2 binding and on the associated screening strategies for anti-SARS-CoV-2 drugs based on blocking mechanisms of pockets.


Assuntos
Preparações Farmacêuticas , Humanos , Peptidil Dipeptidase A , Glicoproteína da Espícula de Coronavírus
5.
Langmuir ; 36(48): 14483-14494, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33211496

RESUMO

The icephobicity property of multifunctional surfaces has been widely studied due to their potential application in the aerospace field. Herein, a controllable CNW/PDMS biomimetic nanocomposite film with a superhydrophobic surface is fabricated. The microcolumns are etched on the surface of the biomimetic nanocomposite to provide superhydrophobicity. Two defense strategies of biomimetic nanocomposites are proposed while passive anti-icing and active electrothermal deicing behaviors of the biomimetic nanocomposite are experimentally studied. It is found that the initial nucleation time of a single water droplet is delayed by 353.3 s on the superhydrophobic surface relative to the hydrophilic surface. The adhesion strength increases with the increase of surface roughness. The heating uniformity on the biomimetic nanocomposite surface was validated by infrared thermography technology. The ice layer is completely melted within 150 s under 40 V voltage captured by a noncontact infrared camera. The proposed strategy was validated by the characterization of the passive anti-icing and active electrothermal deicing property from biomimetic nanocomposites with superhydrophobic microstructure surfaces. Research results show that the two lines of defense collaborative work for an icephobicity system were able to keep biomimetic nanocomposite surfaces ice-free under test conditions.

6.
Eur Radiol ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146791

RESUMO

OBJECTIVES: To develop a nomogram to identify anaplastic lymphoma kinase (ALK) mutations in lung adenocarcinoma patients using clinical, CT, PET/CT, and histopathological features. METHODS: This retrospective study included 399 lung adenocarcinoma patients (129 ALK-rearranged patients and 270 ALK-negative patients) that were randomly divided into a training cohort and an internal validation cohort (4:1 ratio). Clinical factors, radiologist-defined CT features, maximum standard uptake values (SUVmax), and histopathological features were used to construct predictive models with stepwise backward-selection multivariate logistic regression (MLR). The models were then evaluated using the AUC. The integrated model was compared to the clinico-radiological model using the DeLong test to evaluate the role of histopathological features. An associated individualized nomogram was established. RESULTS: The integrated model reached an AUC of 0.918 (95% CI, 0.886-0.950), sensitivity of 0.774, and specificity of 0.934 in the training cohort and an AUC of 0.857 (95% CI, 0.777-0.937), sensitivity of 0.739, and specificity of 0.810 in the validation cohort. The MLR analysis showed that younger age, never smoker, lymph node enlargement, the presence of cavity, high SUVmax, solid or micropapillary predominant histology subtype, and local invasiveness were strong and independent predictors of ALK rearrangements. The nomogram calculated the risk of harboring ALK mutation for lung adenocarcinoma patients and exhibited a good generalization ability. CONCLUSION: Our study demonstrates that histopathological features added value to the imaging characteristics-based model. The nomogram with clinical, imaging, and histopathological features can serve as a supplementary non-invasive tool to evaluate the probability of ALK rearrangement in lung adenocarcinoma. KEY POINTS: • The developed nomogram can accurately predict the probability of lung adenocarcinoma harboring ALK-fused gene. • Pathological analysis is important to predict ALK rearrangement in lung adenocarcinoma. • Lung adenocarcinoma with lepidic predominant growth pattern and TTF-1 negativity is unlikely to have ALK rearrangement.

7.
Drug Deliv ; 27(1): 1474-1490, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33100061

RESUMO

The emergence of nanomaterials for drug delivery provides the opportunity to avoid the side effects of systemic drug administration and injury caused by the removal of tumors, delivering great promise for future cancer treatments. However, the efficacy of current nano drugs is not significantly better than that of the original drug treatments. The important reason is that nano drugs enter the tumor vasculature, remaining close to the blood vessels and unable to enter the tumor tissue or tumor cells to complete the drug delivery process. The low efficiency of drug penetration into tumors has become a bottleneck restricting the development of nano-drugs. Herein, we present a systematic overview of recent advances on the design of nano-drug carriers in drug delivery systems for enhancing drug penetration into tumors. The review is organized into four sections: The drug penetration process in tumor tissue includes paracellular and transcellular transport, which is summarized first. Strategies that promote tumor penetration are then introduced, including methods of remodeling the tumor microenvironment, charge inversion, dimensional change, and surface modification of ligands which promote tissue penetration. Conclusion and the prospects for the future development of drug penetration are finally briefly illustrated. The review is intended to provide thoughts for effective treatment of cancer by summarizing strategies for promoting the endocytosis of nano drugs into tumor cells.

8.
J Integr Neurosci ; 19(3): 469-477, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070526

RESUMO

We investigated the effects of velvet antler polypeptide on cognitive impairment and the underlying mechanisms. Hydrogen peroxide-induced cell injury was used to establish an in vitro model of SH-SY5Y cells. In addition, we established an in vivo mouse model of cognitive impairment using intraperitoneal injections of scopolamine hydrobromide in strain mice. We administered three different doses of velvet antler polypeptide in this mouse model and assessed the influence of velvet antler polypeptide on the morphology of hippocampal neurons, hippocampal neuronal apoptosis, adrenocorticotropic hormone, and corticosterone activities in brain tissue samples, and the molecular and biochemical regulation of B-cell lymphoma-2, B-cell lymphoma-2 Associated X-protein, Cysteine-aspartic acid protease-3, glucocorticoid receptor, mineralocorticoid receptor, and corticotropin-releasing hormone in murine hippocampal neurons. Our data suggest that velvet antler polypeptide decreases glucocorticoid receptor, mineralocorticoid receptor, and corticotropin-releasing hormone levels and regulates the hormones released by the hypothalamic-pituitary-adrenal axis, thus suppressing neuronal apoptosis.

9.
Adv Sci (Weinh) ; 7(18): 1903746, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32999825

RESUMO

As a cause of postoperative complications and early hepatic failure after liver transplantation, liver ischemia/reperfusion injury (IRI) still has no effective treatment during clinical administration. Although the therapeutic potential of mesenchymal stem cells (MSCs) for liver IRI has been previously shown, the underlying mechanisms are not completely clear. It is accepted that MSC-derived extracellular vesicles (MSC-EVs) are newly uncovered messengers for intercellular communication. Herein, it is reported that umbilical cord-derived MSCs (UC-MSCs) improve liver IRI in mice through their secreted EVs. It is also visualized that UC-MSC-EVs mainly concentrate in liver after 6 h of reperfusion. Furthermore, UC-MSC-EVs are found to significantly modulate the membranous expression of CD154 of intrahepatic CD4+ T cells, which is an initiation of inflammatory response in liver and can aggravate liver IRI. Mechanistically, protein mass spectrum analysis is performed and it is revealed that Chaperonin containing TCP1 subunit 2 (CCT2) enriches in UC-MSC-EVs, which regulates the calcium channels to affect Ca2+ influx and suppress CD154 synthesis in CD4+ T cells. In conclusion, these results highlight the therapeutic potential of UC-MSC-EVs in attenuating liver IRI. This finding suggests that CCT2 from UC-MSC-EVs can modulate CD154 expression of intrahepatic CD4+ T cells during liver IRI through the Ca2+-calcineurin-NFAT1 signaling pathway.

10.
J Pers Med ; 10(4)2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33050659

RESUMO

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K-Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein-protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K-Akt-mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

11.
Microb Ecol ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894355

RESUMO

To predict the effects of nitrogen deposition on nitrogen-mineralizing enzyme activity and soil microbial community structure in artificial temperate forests in northern China, we studied the soil properties, nitrogen-mineralizing enzyme activity, and microbial community structure in the soil of a Korean pine plantation in which different concentrations (0, 20, 40, 80 kg N ha-1 year-1) of ammonium nitrate were applied for 5 consecutive years. The results showed that nitrogen addition at different concentrations did not significantly affect the soil pH. High nitrogen addition (80 kg N ha-1 year-1) significantly increased the soil organic matter, ammonium nitrogen, and nitrate nitrogen content in the Korean pine plantation, and ammonium nitrogen was the key factor that influenced the soil fungal community structure. The urease activity under the moderate nitrogen addition treatment (40 kg N ha-1 year-1) was significantly lower than that under the control (0 kg N ha-1 year-1), and the protease activity in the three treatments was also significantly lower than that in the control. There was no significant correlation between microbial community structure and the four mineralizing enzymes. After nitrogen addition at different concentrations, the Simpson and Shannon indexes of soil bacteria decreased significantly under low nitrogen addition (20 kg N ha-1 year-1), but the α-diversity index of soil fungi did not show significant differences under nitrogen addition. The microbial community composition was significantly changed by the different treatments. PLS-DA analysis showed that Tardiphaga was an important genus that made the greatest contribution to the differences in bacterial community composition among treatments, as was Taeniolella for fungal community composition. The low level of nitrogen addition inhibited nitrogen mineralization in the Korean pine plantation by reducing the relative abundances of Nitrosomonadaceae and Betaproteobacteriales and by reducing the abundances of symbiotrophic fungi. Berkelbacteria and Polyporales were bacteria and fungi, respectively, that changed significantly under the high nitrogen addition treatment (80 kg N ha-1 year-1). This study provides more data to support predictions of the changes in nitrogen-mineralizing enzyme activity and microbial community structure in artificial temperate forest soils in response to increased nitrogen deposition.

12.
Cell Death Dis ; 11(9): 746, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32920597

RESUMO

This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China (2017ZX10203205-006-001); National Key R&D Plan (2017YFA0104304); National Natural Science Foundation of China (81770648 81972286); Guangdong Natural Science Foundation (2015A030312013, 2018A0303130305); Science and Technology Program of Guangdong Province (2017B020209004, 20169013, 2017B030314027). This has now been corrected in both the PDF and HTML versions of the Article.

14.
PLoS One ; 15(9): e0238192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991586

RESUMO

This study provides new perspectives on urban development and conservation by exploring the spatial interaction between ecosystem services and urbanization. Limited studies have discussed the interaction between ecosystem services and urbanization; therefore, in this research, the spatial relationship between ecosystem services and urbanization is explored by taking the urban agglomeration in Central Yunnan as an example, and land-use data and economic and social data from 2009 and 2018 are used to determine the interactive impact of urbanization on the urban ecosystem. It is shown that (1) the spatial distribution of the urbanization level of the urban agglomeration in Central Yunnan has significant regional differences, showing a decreasing trend from the urbanized area to the surrounding areas. (2) Another factor with obvious regional differences is the spatial distribution of ecosystem services, which is similar to urbanization in spatial distribution. This difference is mainly caused by the impact of the urbanization level and the change in land use. (3) The spatial distribution and local agglomeration of urbanization and the ecosystem service value of urban agglomeration in Central Yunnan are very similar, and there is a significant negative correlation between the urbanization level and ecosystem service value. The research results have guiding significance for future urban and ecological development in Central Yunnan city.


Assuntos
Ecossistema , Análise Espacial , Urbanização , China , Conservação dos Recursos Naturais
15.
Bioorg Med Chem Lett ; 30(21): 127504, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827631

RESUMO

25-OH ginsenosides are potent and rare prodrugs in natural sources. However current strategies for such modification always end up in undesirable side products and unsatisfied yield that hinders them from further applications. Herein, ginsenoside Rg1 was thoroughly converted into 20(S/R)-Rh1 and 25-OH-20(S/R)-Rh1 by Cordyceps Sinensis in an optimum medium. The chemical correctness of either 25-OH-20(S/R)-Rh1 epimers was validated by LC-IT-TOF-MSn and 13C NMR spectrometry. The biocatalytic pathway was established as Rg1 â†’ 20(S/R)-Rh1 â†’ 25-OH-20(S/R)-Rh1. The molar bioconversion rate for total 25-OH-20(S/R)-Rh1 was calculated to be 82.5%, of which S-configuration accounted for 43.2% while R-configuration 39.3%. These two 25-OH derivatives are direct hydration products from 20(S/R)-Rh1 without other side metabolites, suggesting this is a highly regioselective process. In conclusion, this biocatalytic system could be harnessed to facilitate the preparation of diversified 25-OH ginsenosides with high yields of the target compound and simple chemical background in the reaction mixture.

16.
Cell Death Dis ; 11(8): 657, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814765

RESUMO

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.

17.
Technol Cancer Res Treat ; 19: 1533033820945799, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32729377

RESUMO

Glioma is a common type of tumor in human central nervous system, and it is characterized with high mobility and mortality. The prognosis of patients with advanced glioma remains poor. Thus, it is necessary to develop novel therapeutic approaches for the treatment of this disease. Circular RNAs are a group of noncoding RNAs which have been detected in eukaryotic cells. They are tissue-specific and characterized with a more stable structure compared with linear RNAs. Recently, studies have revealed that certain circular RNAs are involved in biological processes such as gene regulation; however, the functions of most circular RNAs remain unknown and require further investigation. Furthermore, circular RNAs can act as "sponges" of its target microRNA, consequently suppressing their activity. Additionally, impaired expression of circular RNAs is reported in different diseases including cancer. In our study, low expression of circular RNA Scm like with 4 Mbt domains 2 was detected in glioma samples. Furthermore, reduced circRNA Scm like with 4 Mbt domains 2 expression was observed in human glioma cell lines compared to normal astrocyte cells. Additionally, overexpression of circRNA Scm like with 4 Mbt domains 2 suppressed the growth and metastasis of glioma cells in vitro. Moreover, microRNA-182-5p could be a downstream molecule of circRNA Scm like with 4 Mbt domains 2. The influenced of microRNA-182-5p-induced proliferation, migration, and invasion of glioma cells could be abrogated by overexpressed circRNA Scm like with 4 Mbt domains 2. In addition, metastasis suppressor 1 was predicted as a novel target of microRNA-182-5p, and its expression was restored by circRNA Scm like with 4 Mbt domains 2. In summary, our findings provided novel insight into the roles of circRNA Scm like with 4 Mbt domains 2 in glioma. More importantly, circRNA Scm like with 4 Mbt domains 2/microRNA-182-5p/metastasis suppressor 1 axis could be a putative therapeutic target for the treatment of patients with glioma.

18.
Front Microbiol ; 11: 1175, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655513

RESUMO

Rhizobia are capable of establishing compatible symbiosis with their hosts of origin and plants in the cross-nodulation group that the hosts of origin belonged to. However, different from the normal peanut Bradyrhizobium (Type I strains), the Type II strains showed incompatible symbiosis with Vigna radiata. Here, we employed transposon mutagenesis to identify the genetic loci related to this incompatibility in Type II strain CCBAU 53363. As results, seven Tn5 transposon insertion mutants resulted in an increase in nodule number on V. radiata. By sequencing analysis of the sequence flanking Tn5 insertion, six mutants were located in the chromosome of CCBAU 53363, respectively encoding acyltransferase (L265) and hypothetical protein (L615)-unique to CCBAU 53363, two hypothetical proteins (L4 and L82), tripartite tricarboxylate transporter substrate binding protein (L373), and sulfur oxidation c-type cytochrome SoxA (L646), while one mutant was in symbiotic plasmid encoding alanine dehydrogenase (L147). Significant differences were observed in L147 gene sequences and the deduced protein 3D structures between the Type II (in symbiotic plasmid) and Type I strains (in chromosome). Conversely, strains in both types shared high homologies in the chromosome genes L373 and L646 and in their protein 3D structures. These data indicated that the symbiotic plasmid gene in Type II strains might have directly affected their symbiosis incompatibility, whereas the chromosome genes might be indirectly involved in this process by regulating the plasmid symbiosis genes. The seven genes may initially explain the complication associated with symbiotic incompatibility.

19.
Orphanet J Rare Dis ; 15(1): 176, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631372

RESUMO

BACKGROUND AND OBJECTIVE: The purpose of this study was to create a practical CT-based algorithm to differentiate Birt-Hogg-Dubé (BHD) syndrome from other diffuse cystic lung diseases (DCLD). METHODS: The study was a retrospective review of the CT images of 33 patients with BHD syndrome, 33 patients with LAM, and 23 patients with NBNL (non-BHD and non-LAM) among DCLD patients. On the basis of the data collected, the CT images were reviewed again to evaluate the characteristics (size, number, distribution, and morphology) of pulmonary cysts. RESULTS: Lower lung-predominant cysts were more likely to be found in patients with BHD syndrome than in patients with LAM or in the NBNL DCLD group. In the axial distribution, 18 of 33 patients in BHD group had cysts that were predominantly near the mediastinum, and all the patients in the LAM and NBNL DCLD groups had diffuse cysts. The appearance of fusiform cysts was more easily observed in patients in the BHD group. In total, 58% patients in the BHD group had less than 50 lung cysts, while all patients in the non-BHD group had more than 50 lung cysts. The biggest cyst was located in the lower lobe in 28 of 33 patients in the BHD group, while 11 of 33 patients in LAM group and 10 patients in the NBNL DCLD group had the biggest cyst in the lower lobe. CONCLUSION: The pulmonary cysts in patients with BHD tended to be fusiform, less numerous and located predominantly in the lower lobe and near the mediastinum. These radiologic pulmonary features could assist physicians in differentiating BHD from other DCLDs.

20.
Orphanet J Rare Dis ; 15(1): 174, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32615994

RESUMO

BACKGROUND: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidence of benefit from GM-CSG inhalation for mild to moderate aPAP patients is limited. METHODS: In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either the GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients received follow-up for another 18 months without treatment. Physiological features of the patients were analyzed. RESULTS: There were 36 patients (19 in the treatment group, 17 in the control group) included. There were no significant differences in the primary endpoints as measured by the change of alveolar arterial oxygen gradient (A-aDO2) from the baseline values to the values obtained during treatment or during the following 18-month non-treatment observation period [control group vs. treatment group: 0.51 ± 12.09 mmHg vs. -0.35 ± 13.76 mmHg, p = 0.848 (3 month); 1.85 ± 11.21 mmHg vs. 7.31 ± 8.81 mmHg, p = 0.146 (6 months); 6.05 ± 11.14 mmHg vs. 6.61 ± 10.64 mmHg, p = 0.899 (24 months)]). Percentage of diffusion capacity predicted (DLCO%) and percentage of total lung capacity predicted (TLC%), however, were significantly improved in the treatment group by the end of the study (P = 0.010 and 0.027). St. George Respiratory questionnaire (SGRQ) scores were better after 6 months treatment with GM-CSF compared to the control group, and the benefits of treatment were maintained throughout the observation period. No severe side effects were observed during the study. CONCLUSION: Six months of inhaled GM-CSF treatment had no effect on the alveolar-arterial oxygen gradient in patients with mild to moderate pulmonary alveolar proteinosis. There were changes in some clinical or laboratory measures, but no clinically important changes were noted at the end of study. (Clinical Trial Registry: NCT02243228, Registered on September 17, 2014, https://www.clinicaltrials.gov/ct2/show/NCT02243228?term=NCT02243228&draw=2&rank=1 ).

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