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1.
Nanotechnology ; 35(15)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38150723

ABSTRACT

Smart energy storage systems, such as electrochromic supercapacitor (ECSC) integrated technology, have drawn a lot of attention recently, and numerous developments have been made owing to their reliable performance. Developing novel electrode materials for ECSCs that embed two different technologies in a material is an exciting and emerging field of research. To date, the research into ECSC electrode materials has been ongoing with excellent efforts, which need to be systematically reviewed so that they can be used to develop more efficient ECSCs. This mini-review provides a general composition, main evaluation parameters and future perspectives for electrode materials of ECSCs as well as a brief overview of the published reports on ECSCs and performance statistics on the existing literature in this field.

2.
J Integr Plant Biol ; 66(8): 1571-1586, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38874204

ABSTRACT

Deep sowing is a traditional method for drought resistance in maize production, and mesocotyl elongation is strongly associated with the ability of maize to germinate from deep soil. However, little is known about the functional genes and mechanisms regulating maize mesocotyl elongation. In the present study, we identified a plant-specific SIMILAR TO RCD-ONE (SRO) protein family member, ZmSRO1e, involved in maize mesocotyl elongation. The expression of ZmSRO1e is strongly inhibited upon transfer from dark to white light. The loss-of-function zmsro1e mutant exhibited a dramatically shorter mesocotyl than the wild-type in both constant light and darkness, while overexpression of ZmSRO1e significantly promoted mesocotyl elongation, indicating that ZmSRO1e positively regulates mesocotyl elongation. We showed that ZmSRO1e physically interacted with ZmbZIP61, an ortholog of Arabidopsis ELONGATED HYPOCOTYL 5 (HY5) and showed a function similar to that of HY5 in regulating photomorphogenesis. We found that ZmSRO1e repressed the transcriptional activity of ZmbZIP61 toward target genes involved in the regulation of cell expansion, such as ZmEXPB4 and ZmEXPB6, by interfering with the binding of ZmbZIP61 to the promoters of target genes. Our results provide a new understanding of the mechanism by which SRO regulates photomorphogenesis and highlight its potential application in deep sowing-resistant breeding.


Subject(s)
Gene Expression Regulation, Plant , Plant Proteins , Zea mays , Zea mays/genetics , Zea mays/growth & development , Plant Proteins/metabolism , Plant Proteins/genetics
3.
J Cell Physiol ; 236(2): 1375-1390, 2021 02.
Article in English | MEDLINE | ID: mdl-33128793

ABSTRACT

Myeloid-related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest-specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M2 - to M1 -like phenotype by upregulating expression of M1 -related surface receptor proteins and signature M1 -marker genes and by downregulating signature M2 -marker gene expression, which depends on Toll-like receptor 4 and p38 mitogen-activated protein kinase/nuclear factor κB pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14-mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution.


Subject(s)
Antigens, Surface/genetics , Calgranulin A/genetics , Inflammation/genetics , Intercellular Signaling Peptides and Proteins/genetics , Milk Proteins/genetics , Toll-Like Receptor 4/genetics , Animals , Apoptosis/genetics , Cell Polarity/genetics , Humans , Inflammation/metabolism , Inflammation/pathology , Macrophages/metabolism , Macrophages/pathology , Mice , NF-kappa B/genetics , Phagocytosis/genetics , Receptor for Advanced Glycation End Products/genetics , Signal Transduction , Thymocytes/metabolism , Thymocytes/pathology , p38 Mitogen-Activated Protein Kinases/genetics
4.
Int Ophthalmol ; 41(7): 2315-2328, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34117964

ABSTRACT

PURPOSE: To review the published literature on indications and outcomes of DSAEK/DSEK and DMEK for the treatment of failed penetrating keratoplasty. DESIGN: This is a systematic review and single-arm meta-analysis. METHODS: Literature searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Prospective and retrospective studies reporting DSAEK/DSEK or DMEK after failed penetrating keratoplasty were included. Primary outcome measures are graft survival and detachment rates, as well as postoperative visual outcomes. RESULTS: A total of 25 studies with 970 patients/989 eyes were included, comprising 735 patients with 746 eyes which underwent DSAEK/DSEK surgery and 235 patients with 243 eyes which underwent DMEK surgery, all of them following a previously failed PK. There were no randomized controlled studies. In all of the DSAEK-PK studies, the graft failure rate was 18% (10%, 26%), the detachment rate was 15% (9%, 22%) and the rejection rate was 7% (3%, 12%) by the time of the last follow-up. And in all of the DMEK-PK studies, the graft failure rate was 14% (4%, 27%), the detachment rate was 42% (28%, 56%) and the rejection rate was 7% (2%, 16%). The mean visual acuity of the DSAEK-PK and DMEK-PK groups is 0.65 ± 0.18 and 0.43 ± 0.23 logMAR, respectively, at 6 months postoperatively. CONCLUSIONS: Endothelial keratoplasty for treatment of failed penetrating keratoplasty led to improved vision and graft clarity in most recipients. Though graft survival rates and rejection rates were comparable between the two groups, the DMEK-PK group showed better visual outcomes with higher detachment rate.


Subject(s)
Corneal Diseases , Descemet Stripping Endothelial Keratoplasty , Corneal Diseases/surgery , Endothelium, Corneal , Graft Survival , Humans , Keratoplasty, Penetrating , Prospective Studies , Retrospective Studies
5.
Int J Clin Pharm ; 46(1): 14-25, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37294475

ABSTRACT

BACKGROUND: Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid consumption in patients after total hip or knee arthroplasty. AIM: This systematic review and meta-analysis aimed to analyze pain control, opioid consumption, and associated adverse events of perioperative administration of duloxetine after total hip or knee arthroplasty. METHOD: After being registered with PROSPERO (CRD42022323202), the databases of MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception until March 20, 2023, for randomized controlled trials (RCTs). Primary outcomes were the visual Analog Scale (VAS) pain scores at rest (rVAS) and upon ambulation (aVAS). Secondary outcomes were postoperative opioid consumption quantified as oral morphine milligram equivalents (MMEs) and adverse effects of duloxetine. RESULTS: Nine RCTs with 806 cases were included. Duloxetine was associated with lower VAS scores at different times after surgery (24 h, two weeks, and ≥ 3 months). Compared to placebo, perioperative daily duloxetine use significantly reduced daily opioid MMEs at 24 h (standard mean deviation [SMD] -0.71, 95% confidence interval [95% CI] -1.19 to -0.24, P = 0.003), three days (SMD -1.10, 95% CI -1.70 to -0.50, P = 0.0003), and one week (SMD -1.18, 95% CI -1.99 to -0.38, P = 0.004) after surgery. The duloxetine group had a significantly lower rate of nausea (odds ratio 0.62, 95% CI [0.41 to 0.94], P = 0.02) and a higher rate of drowsiness and somnolence (odds ratio 1.87, 95% CI [1.13 to 3.07], P = 0.01) compared to the placebo group. No significant differences were observed in the rates of other adverse events. CONCLUSION:  Perioperative duloxetine significantly decreased postoperative pain and opioid consumption with good safety profiles. Further high quality designed and well-controlled randomized trials are warranted.


Subject(s)
Analgesics, Opioid , Arthroplasty, Replacement, Hip , Humans , Analgesics, Opioid/adverse effects , Duloxetine Hydrochloride/adverse effects , Arthroplasty, Replacement, Hip/adverse effects , Randomized Controlled Trials as Topic , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology
6.
Pest Manag Sci ; 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39183634

ABSTRACT

BACKGROUND: Rice bakanae disease (RBD) has longstanding challenges impacted rice production, which is predominantly induced by Fusarium fujikuroi Nirenberg. Early diagnosis of F. fujikuroi is important to control RBD and improve quality and quantity of rice production. This study presents a novel on-site diagnosis platform combined with CRISPR/LbCas12a and LAMP to detect F. fujikuroi. RESULTS: LAMP amplification of TEF1-α, a characteristic gene of F. fujikuroi were performed, followed with trans-cleavage reaction of LbCas12a, cleaving the single-stranded DNA reporter, which is modified by the terminal fluorophore and quencher groups, producing fluorescence signal. The platform was confirmed with high specificity and sensitivity (LOD <1 aM). Furthermore, we designed a lateral flow strip experiment based on the trans-cleavage activity of LbCas12a, which was identified with similar sensitivity and specificity to the fluorescence detection method. CONCLUSION: In summary, this study achieved a platform with remarkable sensitivity and specificity for F. fujikuroi detection and provide potential for on-site and ultrasensitive diagnostic tools for RBD. © 2024 Society of Chemical Industry.

7.
Sci Total Environ ; 917: 170547, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38296097

ABSTRACT

Microplastics (MPs) transfer from the environment to living organisms is a nonignorable global problem. As a complete metamorphosis insect, the larvae and adult Culex quinquefasciatus mosquito live in aquatic and terrestrial environments, respectively, where they easily access MPs. However, little is known about mosquitoes' potential role in MPs accumulation throughout ecosystems. Therefore, we conducted a study with different MPs particle sizes (0.1/1/10 µm) and concentrations (0.5/5/50 µg/mL) on Cx. quinquefasciatus to address this issue. Once exposed at the young larval stage, MPs could accompany the mosquitoes their entire life. The fluorescence signals of MPs in the larvae were mainly located in the intestines. Its intensity increased (from 3.72 × 106 AU to 5.45 × 107 AU) as the concentrations of MPs increases. The fluorescence signals of MPs were also detected in the blood and skin tissues of mice bitten by adult mosquitoes with MPs containing in their bodies. Mosquitos exposed to MPs showed longer larval pupation and eclosion time as well as lower adult body weight. In addition, MPs significantly reduced the lethal effect of pyrethroid insecticides (97.77 % vs. 48.88 %, p < 0.05) with 15.1 % removal of the deltamethrin concentration. After MPs exposure, the relative abundance of the Cx. quinquefasciatus gut microbiome, such as Wolbachia spp., Elizabethkingia spp., and Asaia spp., changed as the MPs size and concentration changes. Mosquitoes provide a new pathway for MPs accumulation and transfer to higher-level living organisms. Moreover, MPs significantly reduce the control effect of deltamethrin, providing new guidelines for mosquito insecticide application in MPs contamination circumstances.


Subject(s)
Culex , Insect Bites and Stings , Insecticides , Nitriles , Pyrethrins , Animals , Mice , Microplastics , Plastics , Ecosystem , Insecticides/toxicity , Larva , Mammals , Mosquito Control
8.
J Cancer ; 15(8): 2412-2423, 2024.
Article in English | MEDLINE | ID: mdl-38495498

ABSTRACT

Background: Lung cancer and oesophageal cancer are prevalent malignancies with rising incidence and mortality worldwide. While some environmental and behavioural risk factors for these cancers are established, the contribution of genetic factors to their pathogenesis remains incompletely defined. This study aimed to interrogate the intricate genetic relationship between lung cancer and oesophageal cancer and their potential comorbidity. Methods: We utilised linkage disequilibrium score regression (LDSC) to analyse the genetic correlation between oesophageal carcinoma and lung carcinoma. We then employed several approaches, including pleiotropic analysis under the composite null hypothesis (PLACO), multi-marker analysis of genomic annotation (MAGMA), cis-expression quantitative trait loci (eQTL) analysis, and a pan-cancer assessment to identify pleiotropic loci and genes. Finally, we performed bidirectional Mendelian randomisation (MR) to evaluate the causal relationship between these malignancies. Results: LDSC revealed a significant genetic correlation between oesophageal carcinoma and lung carcinoma. Further analysis identified shared gene loci including PGBD1, ZNF323, and WNK1 using PLACO. MAGMA identified enriched pathways and 9 pleiotropic genes including HIST1H1B, HIST1H4L, and HIST1H2BL. eQTL analysis integrating oesophageal, lung, and blood tissues revealed 26 shared genes including TERT, NKAPL, RAD52, BTN3A2, GABBR1, CLPTM1L, and TRIM27. A pan-cancer exploration of the identified genes was undertaken. MR analysis showed no evidence for a bidirectional causal relationship between oesophageal carcinoma and lung carcinoma. Conclusions: This study provides salient insights into the intricate genetic links between lung carcinoma and oesophageal carcinoma. Utilising multiple approaches for genetic correlation, locus and gene analysis, and causal assessment, we identify shared genetic susceptibilities and regulatory mechanisms. These findings reveal new leads and targets to further elucidate the genetic basis of lung and oesophageal carcinoma, aiding development of preventive and therapeutic strategies.

9.
Mol Plant ; 16(3): 571-587, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36681864

ABSTRACT

Alkali stress is a major constraint for crop production in many regions of saline-alkali land. However, little is known about the mechanisms through which wheat responds to alkali stress. In this study, we identified a calcium ion-binding protein from wheat, TaCCD1, which is critical for regulating the plasma membrane (PM) H+-ATPase-mediated alkali stress response. PM H+-ATPase activity is closely related to alkali tolerance in the wheat variety Shanrong 4 (SR4). We found that two D-clade type 2C protein phosphatases, TaPP2C.D1 and TaPP2C.D8 (TaPP2C.D1/8), negatively modulate alkali stress tolerance by dephosphorylating the penultimate threonine residue (Thr926) of TaHA2 and thereby inhibiting PM H+-ATPase activity. Alkali stress induces the expression of TaCCD1 in SR4, and TaCCD1 interacts with TaSAUR215, an early auxin-responsive protein. These responses are both dependent on calcium signaling triggered by alkali stress. TaCCD1 enhances the inhibitory effect of TaSAUR215 on TaPP2C.D1/8 activity, thereby promoting the activity of the PM H+-ATPase TaHA2 and alkali stress tolerance in wheat. Functional and genetic analyses verified the effects of these genes in response to alkali stress, indicating that TaPP2C.D1/8 function downstream of TaSAUR215 and TaCCD1. Collectively, this study uncovers a new signaling pathway that regulates wheat responses to alkali stress, in which Ca2+-dependent TaCCD1 cooperates with TaSAUR215 to enhance PM H+-ATPase activity and alkali stress tolerance by inhibiting TaPP2C.D1/8-mediated dephosphorylation of PM H+-ATPase TaHA2 in wheat.


Subject(s)
Arabidopsis , Arabidopsis/metabolism , Cell Membrane/metabolism , Phosphoprotein Phosphatases/genetics , Proton-Translocating ATPases/genetics , Proton-Translocating ATPases/metabolism , Triticum/genetics , Triticum/metabolism , Intracellular Signaling Peptides and Proteins/metabolism
10.
Parasit Vectors ; 15(1): 353, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36182902

ABSTRACT

BACKGROUND: Both Culex quinquefasciatus and Cx. pipiens molestus are sibling species within Cx. pipiens complex. Even though they are hard to distinguish morphologically, they have different physiological behaviors. However, the molecular mechanisms underlying these differences remain poorly understood. METHODS: Transcriptome sequencing was conducted on antennae of two sibling species. The identification of the differentially expressed genes (DEGs) was performed by the software DESeq2. Database for Annotation, Visualization and Integrated Discovery was used to perform GO pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed with Cytoscape software. The hub genes were screened by the CytoHubba plugin and Degree algorithms. The identified genes were verified by quantitative real-time PCR. RESULTS: Most annotated transcripts (14,687/16,005) were expressed in both sibling species. Among 15 identified odorant-related DEGs, OBP10 was expressed 17.17 fold higher in Cx. pipiens molestus than Cx. quinquefasciatus. Eighteen resistance-related DEGs were identified, including 15 from CYP gene family and three from acetylcholinesterase, in which CYP4d1 was 86.59 fold more highly expressed in C. quinquefasciatus. Three reproductive DEGs were indentified with the expression from 5.01 to 6.55 fold. Among eight vision-related DEGs, retinoic acid receptor RXR-gamma in Cx. pipiens molestus group was more expressed with 214.08 fold. Among the 30 hub genes, there are 10 olfactory-related DEGs, 16 resistance-related DEGs, and four vision-related DEGs, with the highest score hub genes being OBP lush (6041148), CYP4C21 (6044704), and Rdh12 (6043932). The RT-qPCR results were consistent with the transcriptomic data with the correlation coefficient R = 0.78. CONCLUSION: The study provided clues that antennae might play special roles in reproduction, drug resistance, and vision, not only the traditional olfactory function. OBP lush, CYP4C21, and Rdh12 may be key hints to the potential molecular mechanisms behind the two sibling species' biological differences.


Subject(s)
Culex , Acetylcholinesterase , Animals , Culex/physiology , RNA-Seq , Receptors, Retinoic Acid/genetics
11.
Infect Drug Resist ; 15: 223-232, 2022.
Article in English | MEDLINE | ID: mdl-35115791

ABSTRACT

PURPOSE: To elucidate the contribution of a transferable plasmid harboring the bla NDM-1 gene in an Escherichia coli clinical isolate to the spread of resistance determinants. METHODS: Nine extended-spectrum ß-lactamase-producing E. coli were collected from diarrhea samples from a pediatric patient and genetic linkage was investigated through enterobacteriaceae repetitive intragenic consensus polymerase chain reaction (PCR). Bacterial species were identified by 16s rRNA sequencing, susceptibility testing with the use of a BD PhoenixTM-100 Automated Microbiology System, and assessment of virulence genes by PCR. The transferability of bla NDM-1 in E. coli strain TCM3e1 was confirmed by conjugation experiments. Complete sequencing of E. coli strain TCM3e1 was determined with the PacBio and Illumina NovaSeq platforms and the characteristics were analyzed with bioinformatics software. RESULTS: The results showed that all nine E. coli strains were the same clone. E. coli strain TCM3e1 was resistant to 12 antimicrobial agents and carried the virulence gene EAST-1. Conjugation transfer analysis showed that bla NDM-1 was carried on a self-transmissible plasmid. Two copies of the bla NDM-1 gene were present on an IncC plasmid and some resistance genes with two or three copies were located downstream of the bla NDM-1 gene and formed a tandem repeat fragment (bla DNM-1-bleo-sul1- aadA17- dfrA12). CONCLUSION: A transmissible plasmid harboring two copies of the bla NDM-1 gene, including clonal dispersions of the bla NDM-1 gene, was identified in clinical isolates. These findings emphasized the necessity of surveillance of the plasmid-borne bla NDM-1 to prevent dissemination.

12.
ACS Appl Mater Interfaces ; 13(4): 4894-4904, 2021 Feb 03.
Article in English | MEDLINE | ID: mdl-33486955

ABSTRACT

Chemical and physical properties of nanobio interface substantially affect the conformational transitions of adjacent biomolecules. Previous studies have reported the chiral effect and charge effect of nanobio interface on the misfolding, aggregation, and fibrillation of amyloid protein. However, the isomeric effect of nanobio interface on protein/peptides amyloidosis is still unclear. Here, three isomeric nanobio interfaces were designed and fabricated based on the same sized gold nanoclusters (AuNCs) modified with 4-mercaptobenzoic acid (p-MBA), 3-mercaptobenzoic acid (m-MBA), and 2-mercaptobenzoic acid (o-MBA). Then three isomeric AuNCs were employed as models to explore the isomeric effect on the misfolding, aggregation, and fibrillation of Aß40 at nanobio interfaces. Site-specific replacement experiments on the basis of theoretical analysis revealed the possible mechanism of Aß40 interacting with isomeric ligands of AuNCs at the nanobio interfaces. The distance and orientation of -COOH group from the surface of AuNCs can affect the electrostatic interaction between isomeric ligands and the positively charged residues (R5, K16, and K28) of Aß40, which may affect the inhibition efficiency of isomeric AuNCs on protein amyloidosis. Actually, the amyloid fibrillation kinetics results together with atomic force microscope (AFM) images, dynamic light scattering (DLS) results and circular dichroism (CD) spectra indeed proved that all the three isomeric AuNCs could inhibit the misfolding, aggregation and fibrillation of Aß40 in a dose-dependent manner, and the inhibition efficiency was definitely different from each other. The inhibition efficiency of o-MBA-AuNCs was higher than that of m-MBA-AuNCs and p-MBA-AuNCs at the same dosage. These results provide an insight for isomeric effect at nanobio interfaces, and open an avenue for structure-based nanodrug design target Alzheimer's disease (AD) and even other protein conformational diseases.


Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Amyloid/antagonists & inhibitors , Benzoates/pharmacology , Gold/pharmacology , Peptide Fragments/antagonists & inhibitors , Protein Aggregates/drug effects , Salicylates/pharmacology , Sulfhydryl Compounds/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid/chemistry , Amyloid/metabolism , Amyloid/ultrastructure , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Benzoates/chemistry , Gold/chemistry , Humans , Isomerism , Metal Nanoparticles/chemistry , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Protein Folding/drug effects , Salicylates/chemistry , Sulfhydryl Compounds/chemistry
13.
Bioengineered ; 12(1): 196-207, 2021 12.
Article in English | MEDLINE | ID: mdl-33315502

ABSTRACT

It is necessary to explore new molecules for the improvement of precise diagnosis and antitumor therapies in lung cancer. LncRNAs (long non-coding RNAs) play an important role in the regulation of cancer cell malignant behavior and tumor development. In this work, we found that a newly discovered lncRNA, lncRNA PGM5P4-AS1, was lower expressed in lung cancer tissues than adjacent tissues. Then, the lncRNA PGM5P4-AS1 was overexpressed or knocked-down in different lung cancer cells, and its effects on the malignant phenotypes were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, wound healing assay, and transwell assay. The results showed that the overexpression of PGM5P4-AS1 inhibited lung cancer cell proliferation, migration, and invasion activities, while these abilities were prominently promoted by the interference of PGM5P4-AS1. Further, the growth of lung cancer tumors in nude mice was also inhibited by PGM5P4-AS1 overexpression. In mechanism, PGM5P4-AS1 has the binding site of miR-1275 and could positively regulate the expression of LZTS3 via sponging miR-1275. In conclusion, PGM5P4-AS1 could be a potential precise diagnosis and therapeutic target biomarker of lung cancer.


Subject(s)
Lung Neoplasms , MicroRNAs/genetics , RNA, Long Noncoding , Tumor Suppressor Proteins/genetics , Up-Regulation/drug effects , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Leucine Zippers/genetics , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Mice, Nude , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/pharmacology , Tumor Suppressor Proteins/metabolism , Up-Regulation/genetics
14.
Nanoscale ; 12(36): 18834-18843, 2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32895690

ABSTRACT

The misfolding and abnormal amyloid fibrillation of proteins/peptides are associated with more than 20 human diseases. Although dozens of nanoparticles have been investigated for the inhibition effect on the misfolding and fibrillation of pathogenesis-related proteins/peptides, there are few reports on charge effects of nano inhibitors on amyloid fibrillation. Herein, same-sized gold nanoclusters modified with 2-aminoethanethiol hydrochloride (CSH-AuNCs, positively charged in pH 7.4) or 3-mercaptopropionic acid (MPA-AuNCs, negatively charged in pH 7.4) were synthesized and adopted as models to explore the charge effect of nano inhibitors on amylin fibrillation at the nano-bio interface. ThT fluorescence kinetics analysis, AFM images and circular dichroism (CD) spectra showed that electropositive CSH-AuNCs inhibited the misfolding and fibrillation of amylin in a dosage-dependent manner, but electronegative MPA-AuNCs accelerated the misfolding and fibrillation of amylin in a dosage-dependent manner. Moreover, the theoretical and experimental results revealed the interaction mechanism between amylin and ligands of AuNCs at the nano-bio interfaces. Electropositive CSH-AuNCs could be bound to the main nucleating region of amylin via hydrogen bonding and endowed the nanocomplex with more positive net charges (amylin monomer with a positive +26.23 ± 0.80 mV zeta potential), which would inhibit the misfolding and aggregation of amylin via electrostatic repulsion and steric hindrance. In contrast, electronegative MPA-AuNCs could absorb electropositive amylin via strong electrostatic attractions, which accelerated the fibrillation process of amylin via enhancing local concentrations. Moreover, cell experiments showed that both the charged AuNCs had good biocompatibility and electronegetive MPA-AuNCs showed a better protective effect in the amylin-induced cell model than electropositive CSH-AuNCs. These results provide an insight into structure-based nanodrug design for protein conformational diseases.


Subject(s)
Gold , Metal Nanoparticles , Amyloid , Circular Dichroism , Humans , Islet Amyloid Polypeptide
15.
Front Immunol ; 10: 1560, 2019.
Article in English | MEDLINE | ID: mdl-31354717

ABSTRACT

Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis. Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance. However, the biological functions and related molecular bases remain to be elucidated. In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice. Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS. Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4. In addition, these exosomes significantly augmented the proliferation and migration of T lymphocytes. Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice. Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice. Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.


Subject(s)
Chemokines/immunology , Cytokines/immunology , Exosomes/immunology , Sepsis/immunology , Animals , Cecum/immunology , Cell Differentiation/immunology , Disease Models, Animal , Immunomodulation/immunology , Inflammation/immunology , Ligation/methods , Liver/immunology , Lung/immunology , Male , Mice , Mice, Inbred C57BL , Th1 Cells/immunology , Th2 Cells/immunology
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