•The eLHBC wound dressing was inspired by the adhesion mechanism of mussels.•The ε-Poly-l-lysine endowed eLHBC with highly efficient antimicrobial activity.•The BMSCs were encapsulated in eLHBC to ...promoting cell proliferation.•The biomimetic tissue-affinity hydrogel could promote complete skin regeneration.
Hydrogels have gained great attentions as wound dressing. Binding to the tissue and preventing wound infection were the basic requirements for an “ideal dressing”. We employed l-DOPA and ε-Poly-l-lysine to modify thermo-sensitive hydroxybutyl chitosan (HBC) to obtain (l-DOPA) - (ε-Poly-l-lysine)-HBC hydrogels (eLHBC). The eLHBC exhibited an almost 1.5 fold (P < 0.01) increase in wet adhesion strength compared to HBC. Upon the introduction of ε-Poly-l-lysine, eLHBC presented inherent antimicrobial property and prevented wound infection and inflammation response. Bone marrow mesenchymal stem cells (BMSCs) encapsulated in the eLHBC (BMSCs ⊂ eLHBC) could secret cytokins and growth factors via paracrine and promote the migration of fibroblast cells. BMSCs ⊂ eLHBC enhanced the complete skin-thickness wound healing via promoting collagen deposition and inhibiting infection and inflammation in vivo with wound closure rate being above 99 % after 15 days. The bioinspired, tissue-adhesive eLHBC could serve as advanced wound dressings for facilitating tissue repair and regeneration.
Liposomes (LPs), a delivery vehicle for stabilizing drugs, the characteristics of being easy to aggregate and fuse limit its application. Polymer coating is a promising way to tackle these issues. In ...this study, the potential of carboxymethyl chitosan (CMCS) and quaternary ammonium chitosan (TMC)-coated liposomes (CMCS/TMC-LPs) for improving the oral delivery capacity of curcumin (CUR) was explored. CMCS/TMC-LPs were prepared by electrostatic adsorption in a layer-by-layer manner. CMCS/TMC-LPs were spherical and had not obvious change in particle size and morphology after storage at 4 °C for 7 and 14 days. CMCS/TMC-LPs possessed favorable gastric acid tolerance (the cumulative drug release rate <10%) due to stable structure. The hemolysis test and Cell Counting Kit-8 (CCK8) assay appeared satisfactory biocompatibility of CMCS/TMC-LPs. The pharmacokinetics exhibited that oral absolute bioavailability of CUR loaded CMCS/TMC-LPs was about 38%, which was around 6 folds and 3 folds higher than CUR loaded LPs and CUR loaded TMC-LPs, respectively. The in vivo experiments showed that CMCS/TMC-LPs could prolong the retention time of CUR in systemic circulation and generate high level of CUR in liver, spleen and lung. Thus, CMCS/TMC-LPs may be a promising carrier for improving the efficacy and safety of orally administered drugs.
The aim of this study was to develop an effective wound dressing using a temperature-responsive hydroxybutyl chitosan (HBC) based hydrogel. The HBC - chitosan (CS) - dopamine (HCS-DOPA) composite ...hydrogels were prepared by the dopamine self-polymerization at different concentrations (0, 0.5, 1.0 and 2.0 mg/mL), termed as HCS, HCS-DOPA-0.5, HCS-DOPA-1 and HCS-DOPA-2, respectively. The gelling characteristic of HBC hydrogel was not influenced by composite CS and DOPA. The HCS-DOPA composite hydrogels were non-cytotoxic to mouse fibroblast cells (L929), and induced under 5.0% hemolysis rate. In vitro antibacterial studies, composite HCS-DOPA-2 hydrogels exhibited lasting inhibition to S. aureus >8 h. The whole blood test in vitro demonstrated that blood clotting time treated with HCS-DOPA-2 composite hydrogels was shortened to 95.6 s compared with that of HCS in vitro hemostasis. The results suggested that HCS-DOPA-2 composite hydrogels could be applied as a promising wound dressing for hemostasis in vitro.
•The HCS-DOPA hydrogels emerged a special porous structure with uniform pore size and had phase transition between gel-sol.•The composite HCS-DOPA hydrogels were non-cytotoxic to mouse fibroblast cells (L929), and induced under 5.0% hemolysis rate.•The composite HCS-DOPA hydrogels exhibited lasting inhibition of S. aureus more than 8 h in vitro antibacterial studies.•The composite HCS-DOPA hydrogels significantly shortened blood clotting time compared with that of HCS in vitro hemostasis.
As recent studies have described an association between vitamin D and allergic rhinitis, we hypothesized that vitamin D pathway-related genes may be candidate genes for susceptibility to allergic ...rhinitis. Thus, we sought to evaluate whether polymorphisms in the vitamin D receptor (VDR) and CYP2R1 genes are associated with mite-sensitized persistent allergic rhinitis (PER) in a Han Chinese population. A hospital-based case-control study consisting of 519 patients with mite-sensitized PER and 447 healthy controls was conducted. Five single nucleotide polymorphisms (SNPs) in VDR and CYP2R1 were selected for genotyping. The genotype and allele frequencies of rs9729, rs2228570, rs1544410, and rs731236 in VDR as well as rs2060793 in CYP2R1 were not significantly associated with susceptibility to mite-sensitized PER. After stratification analyses, however, both the CT and CT/TT genotypes of rs2228570 in VDR exhibited a significantly decreased risk (CT: adjusted odds ratio (OR)=0.58, 95% confidence intervals (CI)=0.37-0.91;
adjusted OR=0.61, 95% CI=0.40-0.93) of mite-sensitized PER, while the AA genotype of rs2060793 in CYP2R1 exhibited a significantly increased risk (adjusted OR=1.85, 95% CI=1.03-3.34) of PER in the age subgroup of <16 years old. Both the AG and AG/GG genotypes of rs731236 in VDR exhibited a significantly decreased risk (AG: adjusted OR=0.43, 95% CI=0.21-0.89;
adjusted OR=0.46, 95% CI=0.23-0.94) of PER in the female subgroup. Analysis of the locus-locus interactions of VDR and CYP2R1 revealed two models that involved combined SNPs of VDR and CYP2R1 were statistically significant (P<0.05). Our data suggest that age and gender may have an impact on the association of three SNPs (rs2228570, rs731236, and rs2060793) in genes of the vitamin D pathway with the risk of mite-sensitized PER in this Chinese population. The VDR and CYP2R1 variants may be involved in genetic interactions in the pathogenesis of PER.
Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on ...clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs.
haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage after stimulated by lipopolysaccharide (LPS). RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model.
The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at - 80°C, 3 months at - 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 10
particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors.
haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.
Background: The polymorphisms inside microRNA target sites locating in the 3′-UTR region may introduce the microRNA-binding changes, which may regulate the gene expression and correlate with the ...potential diseases. Objectives: We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-β) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population. Methods: In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay. Results: The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08–2.31; GG: adjusted OR = 1.76, 95% CI = 1.09–2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13–2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14–0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25–0.95). No significant association was found between SNPs and the total serum IgE level. Conclusions: In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-β signaling pathway genes.
Because SARS-COV2 entry into cells is dependent on angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increase ACE2 ...activity, the safety of ACEI/ARB usage during the coronavirus disease 2019 (COVID-19) pandemic is a controversial topic. To address that issue, we performed a meta-analysis following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the Embase, MEDLINE, PubMed, and Cochrane Library databases identified 16 case-control studies examining the effect of ACEI/ARB on the incidence of COVID-19 and its severity. ACEI/ARB usage was associated with an increased risk of COVID-19 morbidity (odds ratio (OR) 1.20, 95% confidence interval (CI) 1.07-1.33, P=0.001) among the general population but not in a hypertensive population (OR 1.05, 95% CI 0.90-1.21, P=0.553). ACEI/ARB usage was not associated with an increased risk of COVID-19 morbidity (coefficient 1.00, 95% CI 1.00-1.00, P=0.660) when we adjusted for hypertension in the general population. ACEI/ARB usage was also not associated with an increased risk of severe illness (OR 0.90, 95%CI 0.55-1.47, P=0.664) or mortality (OR 1.43, 95%CI 0.97-2.10, P=0.070) in COVID-19 patients. Our meta-analysis revealed that ACEI/ARB usage was not associated with either the increased risk of SARS-COV2 infection or the adverse outcomes in COVID-19 patients.
Purpose
Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been ...systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China.
Methods
A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed.
Results
Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine
ADA2
causative variants were identified, six of which were novel.
Conclusion
To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.
Poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP))-based gel polymer electrolyte (GPE) membranes are prepared by phase inversion method using urea as pore-forming agent and ...dimethylformamide as solvent, respectively, and the desired polymer electrolytes are obtained after being immersed the as-prepared polymer electrolyte membranes into liquid electrolytes for 1 h. Physicochemical properties of the GPEs are investigated by SEM, XRD, FT-IR, TG-DSC, EIS and LSV. When the weight ratio of urea to P(VDF-HFP) is up to 0.6:4, the results show that the polymer electrolyte membrane presents the most uniform surface with abundant interconnected micro-pores and excellent thermal stability, in which the ionic conductivity at room temperature can reach 2.671 mS cm−1 and the reciprocal temperature dependence of ionic conductivity follows Arrhenius relationship. The interfacial resistance of the Li/GPE/Li simulated cell with 0.6 g urea can rapidly increase to a steady value about 650 Ω cm−1 from the initial value about 475 Ω cm−1 during 15 days storage at 30 °C. The polymer electrolyte with 0.6 g urea can be stable at 5.3 V (vs Li/Li+) at room temperature and the assembled Li/GPE/LiCoO2 coin cell can also show good rate and cycle performance.
Reciprocal temperature dependence of ionic conductivity of different polymer electrolytes. Display omitted
•P(VDF-HFP)-based GPE using urea as pore-forming agent was prepared by phase inversion method.•The GPE with 0.6 g urea show the smoothest surface morphology with ionic conductivity at room temperature about 2.671 mS cm−1.•Mechanism of ionic conductivity follows Arrhenius relationship and interfacial performance gains much improvement.•The assembled Li/GPE/LiCoO2 coin cell shows good rate and cycle performance.
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