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1.
Sci Rep ; 10(1): 16484, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020497

RESUMO

The cytochrome cd1-containing nitrite reductase, nirS, plays an important role in biological denitrification. Consequently, investigating the presence and abundance of nirS is a commonly used approach to understand the distribution and potential activity of denitrifying bacteria, in addition to denitrifier communities. Herein, a rapid method for detecting nirS gene with loop-mediated isothermal amplification (LAMP) was developed, using Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1) as model microorganism to optimize the assay. The LAMP assay relied on a set of four primers that were designed to recognize six target sequence sites, resulting in high target specificity. The limit of detection for the LAMP assay under optimized conditions was 1.87 pg/reaction of genomic DNA, which was an order of magnitude lower than that required by conventional PCR assays. Moreover, it was validated that P. aeruginosa PAO1 cells as well as genomic DNA could be directly used as template. Only 1 h was needed from the addition of bacterial cells to the reaction to the verification of amplification success. The nirS gene of P. aeruginosa PAO1 in spiked seawater samples could be detected with both DNA-template based LAMP assay and cell-template based LAMP assay, demonstrating the practicality of in-field use.

2.
BMC Cancer ; 20(1): 966, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023539

RESUMO

BACKGROUND: Nuclear factor of activated T cells 2 (NFAT2) has been reported to regulate the development and malignancy of few tumors. In this study, we aimed to explore the effect of NFAT2 expression on cell fate of HepG2 cell and its potential mechanisms. METHODS: Firstly, the pcDNA3.1-NFAT2 plasmid was transfected into HepG2 cells to construct NFAT2 overexpressed HepG2 cells. Then, the chemical count kit-8 cell viability assay, Annexin V-FITC apoptosis detection, EdU labeling proliferation detection, transwell and wound healing experiments were performed. The expression of Egr2 and FasL, and the phosphorylation of AKT and ERK, after ionomycin and PMA co-stimulation, was detected, while the Ca2+ mobilization stimulated by K+ solution was determined. At last, the mRNA and protein expression of NFAT2, Egr2, FasL, COX-2 and c-myc in carcinoma and adjacent tissues was investigated. RESULTS: The NFAT2 overexpression suppressed the cell viability, invasion and migration capabilities, and promoted apoptosis of HepG2 cells. NFAT2 overexpression induced the expression of Egr2 and FasL and suppressed the phosphorylation of AKT and ERK. The sensitivity and Ca2+ mobilization of HepG2 cells was also inhibited by NFAT2 overexpression. Compared with adjacent tissues, the carcinoma tissues expressed less NFAT2, Egr2, FasL and more COX-2 and c-myc. CONCLUSION: The current study firstly suggested that NFAT2 suppressed the aggression and malignancy of HepG2 cells through inducing the expression of Egr2. The absence of NFAT2 and Egr2 in carcinoma tissues reminded us that NFAT2 may be a promising therapeutic target for hepatocellular carcinoma treatment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33029688

RESUMO

Homologous feeder culture system can efficiently promote the proliferation of embryonic germ (EG) cells or embryonic stem (ES) cells while avoiding contamination by exogenous proteins and pathogens. In this study, we compared the potency of using homologous porcine embryonic fibroblasts (PEFs), gonadal stromal cells (GSCs), porcine adipose-derived stem cells (PASCs), or porcine amniotic fluid stem (PAFS) cells as feeder cells for porcine EG growth, with the commonly used mouse embryonic fibroblasts (MEFs). We compared the feeder cell growth rates; secretion of growth factors including stem cell factor (SCF), basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (LIF); the effects of growth factors on porcine PGC growth; and EG growth rates when individual cells were used as feeders. Our results showed that feeder cells secreted limited amounts of growth factors, and supplementation of growth factors can significantly improve the formation of EG colonies and number of passages (P < 0.05). GSC and PEF were more suitable for EG growth because of their faster growth rate and their support on EG growth. In conclusion, this study identified novel homologous cells that can be used for EG production.

4.
Nat Commun ; 11(1): 4930, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004804

RESUMO

Inference of causality between gene expression and complex traits using Mendelian randomization (MR) is confounded by pleiotropy and linkage disequilibrium (LD) of gene-expression quantitative trait loci (eQTL). Here, we propose an MR method, MR-link, that accounts for unobserved pleiotropy and LD by leveraging information from individual-level data, even when only one eQTL variant is present. In simulations, MR-link shows false-positive rates close to expectation (median 0.05) and high power (up to 0.89), outperforming all other tested MR methods and coloc. Application of MR-link to low-density lipoprotein cholesterol (LDL-C) measurements in 12,449 individuals with expression and protein QTL summary statistics from blood and liver identifies 25 genes causally linked to LDL-C. These include the known SORT1 and ApoE genes as well as PVRL2, located in the APOE locus, for which a causal role in liver was not known. Our results showcase the strength of MR-link for transcriptome-wide causal inferences.

5.
Clin Neuroradiol ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006652

RESUMO

PURPOSE: To explore changes in functional connectivity (FC) within the sensorimotor network (SMN) and the relationship between the SMN and bilateral thalamus in patients with thalamic infarction (TI) using resting state functional magnetic resonance imaging (rs-fMRI). Also determined was whether those measures are useful for monitoring the functional recovery of somatosensory deficits. METHODS: The study included 31 patients with TI presenting somatosensory dysfunction and 31 controls who underwent clinical assessments and MRI scanning at 6 months after a stroke. An independent component analysis was used to identify the SMN. The mean time courses of SMN activity were extracted for each subject, and FC with the bilateral thalamus was assessed. Differences in connectivity strength were compared between groups. Finally, we correlated the altered FC values with clinical data from patients with TI. RESULTS: Compared to controls, patients with TI showed decreases in FC within SMN in the ipsilesional posterior central gyrus (PCG) (Z-score = -4.581, cluster size = 171), but presented increased FC within the SMN in the ipsilesional supplementary motor area (SMA) (Z-score = 4.648, cluster size = 46). The FC values of the ipsilesional SMA correlated with the somatosensory function score of patients with TI (r = 0.426, P = 0.027). Increased FC was observed between the SMN and bilateral thalamus in patients with TI. The region exhibiting increased FC was adjacent to the lesion in the affected thalamus, while the area with increased FC overlapped the location of the lesion when the lesion was mirrored onto the unaffected thalamus. CONCLUSION: The increased FC in the ipsilesional SMA and between the SMN and perilesional thalamus might reflect functional reorganization in patients with TI presenting somatosensory deficits.

6.
Pharmacol Res ; : 105111, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065284

RESUMO

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

7.
Biol Res ; 53(1): 47, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066819

RESUMO

Nitrogen is the main limiting nutrient after carbon, hydrogen and oxygen for photosynthetic process, phyto-hormonal, proteomic changes and growth-development of plants to complete its lifecycle. Excessive and inefficient use of N fertilizer results in enhanced crop production costs and atmospheric pollution. Atmospheric nitrogen (71%) in the molecular form is not available for the plants. For world's sustainable food production and atmospheric benefits, there is an urgent need to up-grade nitrogen use efficiency in agricultural farming system. The nitrogen use efficiency is the product of nitrogen uptake efficiency and nitrogen utilization efficiency, it varies from 30.2 to 53.2%. Nitrogen losses are too high, due to excess amount, low plant population, poor application methods etc., which can go up to 70% of total available nitrogen. These losses can be minimized up to 15-30% by adopting improved agronomic approaches such as optimal dosage of nitrogen, application of N by using canopy sensors, maintaining plant population, drip fertigation and legume based intercropping. A few transgenic studies have shown improvement in nitrogen uptake and even increase in biomass. Nitrate reductase, nitrite reductase, glutamine synthetase, glutamine oxoglutarate aminotransferase and asparagine synthetase enzyme have a great role in nitrogen metabolism. However, further studies on carbon-nitrogen metabolism and molecular changes at omic levels are required by using "whole genome sequencing technology" to improve nitrogen use efficiency. This review focus on nitrogen use efficiency that is the major concern of modern days to save economic resources without sacrificing farm yield as well as safety of global environment, i.e. greenhouse gas emissions, ammonium volatilization and nitrate leaching.

8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1726-1732, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067981

RESUMO

OBJECTIVE: To analyze the affecting factors of hemoglobin changes in apheresis red blood cells (RBCs), and to establish a predictive model for the evaluation of apheresis. METHODS: The clinical data of 130 patients undergoing selective surgery for apheresis autologous RBCs from January 2017 to December 2018 were collected. The change of hemoglobin and its affecting factors before and after apheresis were analyzed. The predictive model of the hemoglobin change was established by machine learning algorithm and compared with the theoretical predictive model. RESULTS: The average Hb level in the 300 ml autologous RBC group decreased by 22.61±8.85 g/L, and the average Hb in 400 ml group decreased by 29.08±7.25 g/L. The change of Hb was mainly affected by Hb level before apheresis and peripheral circulation blood volume (P<0.05). Sex, age, and the interval time between blood collection and operation not significantly influenced Hb change (P>0.05). The initially established predictive model by the machine learning (MAE 6.27) is superior to the theoretical predictive model (MAE 8.11). CONCLUSION: The predictive model established by the machine learning can provide a reference for more accurate evaluation of apheresis autologous red blood cells.

9.
BMC Genomics ; 21(1): 719, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33069230

RESUMO

BACKGROUND: Flammulina filiformis (previously known as Asian F. velutipes) is a popular commercial edible mushroom. Many bioactive compounds with medicinal effects, such as polysaccharides and sesquiterpenoids, have been isolated and identified from F. filiformis, but their biosynthesis and regulation at the molecular level remains unclear. In this study, we sequenced the genome of the wild strain F. filiformis Liu355, predicted its biosynthetic gene clusters (BGCs) and profiled the expression of these genes in wild and cultivar strains and in different developmental stages of the wild F. filiformis strain by a comparative transcriptomic analysis. RESULTS: We found that the genome of the F. filiformis was 35.01 Mb in length and harbored 10,396 gene models. Thirteen putative terpenoid gene clusters were predicted and 12 sesquiterpene synthase genes belonging to four different groups and two type I polyketide synthase gene clusters were identified in the F. filiformis genome. The number of genes related to terpenoid biosynthesis was higher in the wild strain (119 genes) than in the cultivar strain (81 genes). Most terpenoid biosynthesis genes were upregulated in the primordium and fruiting body of the wild strain, while the polyketide synthase genes were generally upregulated in the mycelium of the wild strain. Moreover, genes encoding UDP-glucose pyrophosphorylase and UDP-glucose dehydrogenase, which are involved in polysaccharide biosynthesis, had relatively high transcript levels both in the mycelium and fruiting body of the wild F. filiformis strain. CONCLUSIONS: F. filiformis is enriched in a number of gene clusters involved in the biosynthesis of polysaccharides and terpenoid bioactive compounds and these genes usually display differential expression between wild and cultivar strains, even in different developmental stages. This study expands our knowledge of the biology of F. filiformis and provides valuable data for elucidating the regulation of secondary metabolites in this unique F. filiformis strain.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33003144

RESUMO

ABO incompatibility has emerged as the premier reason for hemolytic disease of the fetus and newborn (HDFN). It always occurs in the offspring of blood group O mother. We present a rare case that the fetus of group A got HDFN caused by the anti-group A immunoglobulin G from a group B mother. The direct Coombs test of the fetus blood was negative, but the indirect Coombs test on A1 standard blood cells was strong positive (4+). The acid release test of antibody on the membrane of red blood cells to A1 standard blood cells was also strong positive (4+). Bilirubin of the fetus reached the threshold of exchange transfusion, but she just received 4 days' phototherapy and 2.2 g albumin intravenous injection, with no packed blood cells transfusion, because her family refused, and came to a favorable outcome. This case reminds us not to ignore the possibility of HDFN in offspring of mothers with non-O blood group.

11.
Biostatistics ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040145

RESUMO

In recent biomedical research, genome-wide association studies (GWAS) have demonstrated great success in investigating the genetic architecture of human diseases. For many complex diseases, multiple correlated traits have been collected. However, most of the existing GWAS are still limited because they analyze each trait separately without considering their correlations and suffer from a lack of sufficient information. Moreover, the high dimensionality of single nucleotide polymorphism (SNP) data still poses tremendous challenges to statistical methods, in both theoretical and practical aspects. In this article, we innovatively propose an integrative functional linear model for GWAS with multiple traits. This study is the first to approximate SNPs as functional objects in a joint model of multiple traits with penalization techniques. It effectively accommodates the high dimensionality of SNPs and correlations among multiple traits to facilitate information borrowing. Our extensive simulation studies demonstrate the satisfactory performance of the proposed method in the identification and estimation of disease-associated genetic variants, compared to four alternatives. The analysis of type 2 diabetes data leads to biologically meaningful findings with good prediction accuracy and selection stability.

12.
Allergy ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040337

RESUMO

BACKGROUND: The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic. MEASURE: Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11,766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. 63 healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset. RESULTS: A combination test of NAT and serological testing for IgM antibody with discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N specific antibodies, S1 specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17d to 25d, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months. CONCLUSION: Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health and immunization strategies.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33044149

RESUMO

A novel, Gram-stain-positive, aerobic, non-spore-forming, non-motile and irregular rod-shaped bacterium designated Q22T was isolated from the rhizosphere soil of mangrove plant, Kandelia candel collected in Zhangzhou, Fujian province, China. Strain Q22T was able to grow at 10-40 °C (optimum 30 °C), pH 5.5-9.0 (optimum 7.0-8.0) and with 0-5.0% (w/v) NaCl (optimum 1.0 %). The genomic DNA G+C content was 71.9%. The average nucleotide identity, and in silico DNA-DNA hybridization values between strain Q22T and the reference strains were 79.7-88.9% and 22.6-37.4%, respectively. The predominant isoprenoid quinone was MK-12 and the major fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The major polar lipids of strain Q22T were diphosphatidylglycerol, phosphatidylglycerol, one glycolipid and three unidentified lipids. The strain Q22T contained 2,4-diaminobutyric acid, alanine acid, glutamic acid and glycine in the peptidoglycans. The phylogenetic analysis and genotypic features, along with the phenotypic and chemotaxonomic characteristics, indicate that strain Q22T represents a novel species of the genus Agromyces, for which the name Agromyces kandeliae sp. nov. is proposed. The type strain is Q22T (=MCCC 1K03340T= KCTC 39961T).

14.
J Hypertens ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33044381

RESUMO

OBJECTIVE: The study aimed to explore the association of age at menarche with hypertension and whether adiposity and insulin resistance mediated the association in rural Chinese women. METHODS: We conducted a cross-sectional study enrolling 7518 women (median age 56 years) from a rural Chinese area from 2013 to 2014. Adiposity was measured by BMI and waist circumference, and insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR) index. Odds ratios (ORs) and 95% confidence limits (Cls) for the association of age at menarche with hypertension were estimated by using multivariate logistic regression models. The contribution of adiposity and insulin resistance to the association was estimated by mediation analysis. RESULTS: Among 7518 women, 3187 (42.39%) had hypertension. Age at menarche was inversely associated with hypertension (per additional year of menarche, OR = 0.965, 95% Cl: 0.935-0.995). BMI or waist circumference and HOMA-IR completely mediated the association of age at menarche with hypertension (for BMI and HOMA-IR: total indirect effect: OR = 0.970, 95% Cl: 0.962-0.978 and direct effect: OR = 0.994, 95% Cl: 0.963-1.026; for waist circumference and HOMA-IR: total indirect effect: OR = 0.981, 95% Cl: 0.973-0.988 and direct effect: OR = 0.983, 95% Cl: 0.952-1.014). CONCLUSION: Early age at menarche was positively associated with hypertension. Adiposity and insulin resistance seemed to be two vital mediators of the association between age at menarche and hypertension in rural Chinese women.

15.
Plant Physiol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037127

RESUMO

Recent studies have shown that loss of pollen-S function in S4' pollen from sweet cherry (Prunus avium) is associated with a mutation in an S haplotype-specific F-box 4 (SFB4) gene. However, how this mutation leads to self-compatibility is unclear. Here, we examined this mechanism by analyzing several self-compatible sweet cherry varieties. We determined that mutated SFB4 (SFB4') in S4' pollen (pollen that harboring SFB4' gene) is approximately 6 kDa shorter than wild-type SFB4 due to a premature termination caused by a 4-nucleotide deletion. SFB4' did not interact with S-RNase. However, a protein in S4' pollen ubiquitinated S-RNase, resulting in its degradation via the 26S proteasome pathway, indicating that factors in S4' pollen other than SFB4 participate in S-RNase recognition and degradation. To identify these factors, we used S4-RNase as a bait to screen S4' pollen proteins. Our screen identified the protein encoded by S4-SLFL2, a low-polymorphic gene that is closely linked to the S-locus. Further investigations indicate that SLFL2 ubiquitinates S-RNase, leading to its degradation. Subcellular localization analysis showed that SFB4 is primarily localized to the pollen tube tip, whereas SLFL2 is not. When S4-SLFL2 expression was suppressed by antisense oligonucleotide treatment in wild-type pollen tubes, pollen still had the capacity to ubiquitinate S-RNase; however, this ubiquitin-labeled S-RNase was not degraded via the 26S proteasome pathway, suggesting that SFB4 does not participate in the degradation of S-RNase. When SFB4 loses its function, S4-SLFL2 might mediate the ubiquitination and degradation of S-RNase, which is consistent with the self-compatibility of S4' pollen.

16.
ChemSusChem ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33047881

RESUMO

Polyvinyl chloride (PVC) is the world's third-most widely produced plastic polymer. Directly transforming PVC to carbonaceous materials for CO 2 capture provides an environmentally-friendly attractive strategy to recycle plastics. In this work, we developed a simple and effective method to prepare PVC-derived carbon spheres. In this method, the classical "spheroidization" process shaped the original PVC powders into millimeter spheres, and special dehalogenation and cross-linking process in the presence of a phase transfer catalyst transferred thermoplasticity of the PVC-spheres into thermosetting, which stabilized the shape. Furthermore, by rationally adjusting the activation conditions, the porous structure of the carbon spheres was well optimized. With the specific surface area up to 1738 m 2 /g and the developed microporous structure, the as-prepared carbon spheres possess not only excellent performance in pure CO 2 adsorption (8.93 mmol g-1, 39.3 wt.% at 0 °C and 5.47 mmol g-1, 24.1 wt.% at 25 °C), but also outstanding adsorption capacity and recyclability in low concentration CO 2 capture, even superior to conventional molecular sieves.

17.
Anal Bioanal Chem ; 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33011840

RESUMO

A sensitive and portable microfluidic electrochemical array device (µFED) was developed for the immunoassay of trace amounts of human cardiac troponin I (cTnI), which is an attractive biomarker for acute myocardial infarction (AMI). The classical "sandwich" method was adopted for the immunoassay. The capture antibody was immobilized using a self-assembled monolayer (SAM) technique, and the process was reorganized to be compatible with the bonding process. The detection antibody was labeled with alkaline phosphatase (AP) for signal amplification. The performance of the µFED was improved by eliminating the shielding effect of the microelectrode array (MEA) integrated in the µFED. The effects of the interstice and the width of the MEA on the response peak current were analyzed and simulated. The concentration gradient, about 3% of the gradient at the surface, was considered as the criterion for estimation of the optimal interstice between electrodes, and its effectiveness was proved. A stable and miniaturized reference electrode was integrated in the µFED, and its potential deviation was less than 5 mV in 15 min. These efforts resulted in the enhanced immunoassay performance of the µFED. A low limit of detection of about 5 pg/mL was obtained in serum samples, and the response current was proportional to the logarithm of concentration from 50 pg/mL to 1 µg/mL. The immunoassay process was accomplished in 15 min. The µFED was thus qualified and is a promising candidate for point-of-care immunoassay of cTnI. Graphical abstract.

18.
Adv Healthc Mater ; : e2001327, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000915

RESUMO

Cyanine is a class of fluorescent dye with meritorious fluorescence properties and has motivated numerous researchers to explore its imaging capabilities by miscellaneous structural modification and functionalization strategies. The covalent conjugation with other functional molecules represents a distinctive design strategy and has shown immense potential in both basic and clinical research. This review article summarizes recent achievements in cyanine conjugate-based probes for biomedical imaging. Particular attention is paid to the conjugation with targeting warheads and other contrast agents for targeted fluorescence imaging and multimodal imaging, respectively. Additionally, their clinical potential in cancer diagnostics is highlighted and some concurrent impediments for clinical translation are discussed.

19.
J Mater Chem B ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001117

RESUMO

Bioactive hydrogels based on naturally-derived polymers are of great interest for regenerative medicine applications. Among naturally-derived polymers, silk fibroin has been extensively explored as a biomaterial for tissue engineering due to its unique mechanical properties. Here, we demonstrate the rapid gelation of cell-laden silk fibroin hydrogels by visible light-induced crosslinking using riboflavin as a photo-initiator, in presence of an electron acceptor. The gelation kinetics were monitored by in situ photo-rheometry. Gelation was achieved in minutes and could be tuned owing to its direct proportionality to the electron acceptor concentration. The concentration of the electron acceptor did not affect the elastic modulus of the hydrogels, which could be altered by varying the polymer content. Further, the biocompatible riboflavin photo-initiator combined with sodium persulfate allowed for the encapsulation of cells within silk fibroin hydrogels. To confirm the cytocompatibility of the silk fibroin formulations, three cell types (articular cartilage-derived progenitor cells, mesenchymal stem cells and dental-pulp-derived stem cells) were encapsulated within the hydrogels, which associated with a viability >80% for all cell types. These results demonstrated that fast gelation of silk fibroin can be achieved by combining it with riboflavin and electron acceptors, which results in a hydrogel that can be used in tissue engineering and cell delivery applications.

20.
J Nat Prod ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006888

RESUMO

Anti-cardiac fibrosis (CF) is one of the key therapeutic strategies for the treatment of various heart diseases. Therefore, development of drugs targeting CF is promising. However, there are very few studies that systemically explore effective drugs for CF. It has been known that many natural compounds display antifibrosis effects. In this work, we aim to build an integrated model for systematic pursuit of anti-CF agents from natural compounds. We first constructed a heart-specific CF marker-gene-centered functional gene module (HCFM) that represents a set of genes specifically involved in CF based on the CF marker genes and known gene coexpression knowledge. Then, we extracted transcriptional data induced by natural compounds from the Gene Expression Omnibus database. The anti-CF effects of compounds were evaluated by the correlation of HCFM in the compound-induced gene expression profiles by gene set enrichment analysis. Finally, the anti-CF effect of a top-predicted natural monomer, schisantherin A, was experimentally validated in the myocardial infarction animal model. This strategy integrating different types of technologies is expected to help create new opportunities for development of drugs targeting CF.

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