1.FLT3 ligand regulates expansion of regulatory T-cells induced by regulatory dendritic cells isolated from gut-associated lymphoid tissues through the Notch pathway.
Na LI ; Jingwei MAO ; Haiying TANG ; Xiaoyan TAN ; Jian BI ; Hao WU ; Xiuli CHEN ; Yingde WANG
Chinese Medical Journal 2025;138(13):1595-1606
BACKGROUND:
Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process.
METHODS:
DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice.
RESULTS:
CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice.
CONCLUSION
The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals
;
T-Lymphocytes, Regulatory/immunology*
;
Dendritic Cells/immunology*
;
Mice
;
Mice, Inbred BALB C
;
Membrane Proteins/metabolism*
;
Receptors, Notch/metabolism*
;
Lymphoid Tissue/metabolism*
;
Signal Transduction/physiology*
;
Coculture Techniques
;
Flow Cytometry
2.Near-infrared excited graphene oxide/silver nitrate/chitosan coating for improving antibacterial properties of titanium implants.
Yifan WANG ; Yingde XU ; Xuefeng ZHANG ; Jingyu LIU ; Jintong HAN ; Shengli ZHU ; Yanqin LIANG ; Shuilin WU ; Zhenduo CUI ; Weijia LÜ ; Zhaoyang LI
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(8):937-944
OBJECTIVE:
To design and construct a graphene oxide (GO)/silver nitrate (Ag3PO4)/chitosan (CS) composite coating for rapidly killing bacteria and preventing postoperative infection in implant surgery.
METHODS:
GO/Ag3PO4 composites were prepared by ion exchange method, and CS and GO/Ag3PO4 composites were deposited on medical titanium (Ti) sheets successively. The morphology, physical image, photothermal and photocatalytic ability, antibacterial ability, and adhesion to the matrix of the materials were characterized.
RESULTS:
The GO/Ag3PO4 composites were successfully prepared by ion exchange method and the heterogeneous structure of GO/Ag3PO4 was proved by morphology phase test. The heterogeneous structure formed by Ag3PO4 and GO reduced the band gap from 1.79 eV to 1.39 eV which could be excited by 808 nm near-infrared light. The photothermal and photocatalytic experiments proved that the GO/Ag3PO4/CS coating had excellent photothermal and photodynamic properties. In vitro antibacterial experiments showed that the antibacterial rate of the GO/Ag3PO4/CS composite coating against Staphylococcus aureus reached 99.81% after 20 minutes irradiation with 808 nm near-infrared light. At the same time, the composite coating had excellent light stability, which could provide stable and sustained antibacterial effect.
CONCLUSION
GO/Ag3PO4/CS coating can be excited by 808 nm near infrared light to produce reactive oxygen species, which has excellent antibacterial activity under light.
Chitosan
;
Silver Nitrate
;
Titanium
;
Anti-Bacterial Agents/pharmacology*
;
Coloring Agents
3.Analysis of intestinal flora in patients with chronic rhinosinusitis based on highthroughput sequencing.
Jiayu HUANG ; Liping WANG ; Xiaoqin WU ; Huanjun CHEN ; Xiuli FU ; Shaohua CHEN ; Tao LIU
Journal of Southern Medical University 2020;40(9):1319-1324
OBJECTIVE:
To investigate the changes in diversity, relative abundance and distribution of intestinal flora in patients with chronic rhinosinusitis and nasal polyps (CRSwNP) using high-throughput sequencing technology identify the intestinal flora significantly related to pathogenesis and progression of CRSwNP.
METHODS:
Ten patients with CRSwNP hospitalized in the Department of Otolaryngology-Head and Neck Surgery of Guangdong Provincial People's Hospital were selected as the case group with 10 healthy volunteers recruited in the same period as the control group. Fecal genomic DNA extraction kit was used to extract the DNA in the fecal samples, and the DNA fragment length was measured and quantified. The V3 and V4 highly variable regions of the 16S rDNA gene of prokaryotes were amplified followed by library construction, Illumina MiSeq sequencing, sequence alignment and species identification analysis. The relative abundance, diversity and distribution characteristics of the intestinal flora were analyzed, and the relevant metabolic pathways were predicted.
RESULTS:
Compared with the control group, the patients with CRSwNP had significant changes in the overall structure of the intestinal flora, highlighted by increased abundance of Saccharopolyspora and decreased contents of , , and . Among the metabolic pathways predicted to be associated with CRSwNP, 9 showed significant changes in patients with CRSwNP as compared with the control group ( < 0.05).
CONCLUSIONS
Patients with CRSwNP have significant changes in the structural characteristics of intestinal flora related with multiple metabolic pathways, and these changes may play an important role in the development of chronic rhinosinusitis.
4.Value of early application of different doses of amino acids in parenteral nutrition among preterm infants.
Zhi-Juan LIU ; Guo-Sheng LIU ; Yong-Ge CHEN ; Hui-Li ZHANG ; Xue-Fen WU
Chinese Journal of Contemporary Pediatrics 2015;17(1):53-57
OBJECTIVETo study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants.
METHODSThis study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied.
RESULTSThe maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05).
CONCLUSIONSParenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.
Amino Acids ; administration & dosage ; Birth Weight ; Blood Urea Nitrogen ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Nutritional Status ; Parenteral Nutrition ; adverse effects
5.Metabolism and efficacy study of ~(125)I-anti-AFP administrated by interventional route for primary liver cancer
Kehe CHEN ; Yingde WU ; Zhihui LIU
China Oncology 2000;0(06):-
Purpose:To study the characteristics of biological distribution in vivo and therapeutic efficacy of 125 I-anti-alpha-fetoprotein(AFP) antibody when administrated by the hepatic artery , and discussion of multi-modal therapy by transcatheter arterial chemoembolization(TACE) and immunization therapy. Methods:21 patients with moderately and advanced primary liver cancer (PLC) were treated by 125 I-anti -alpha-fetoprotein which was administered via hepatic artery, together with TACE and CD3AK cell by intravenous infusion to,detect the pharmacokinetic parameters and metabolism for 125 I-anti-AFP in vivo, and observe the efficacy of multi-modal treatment. Results:The radioactivity half-life time of ?phase (T 1/2 ?) and ? phase ( T 1/2 ?) for 125 I-anti-AFP antibodies was 1.85?1.79 and 156.46?65 hr,respectively; half-excretion time from urine was 94 hr, radiation intensity measured at body surface of organ suggested that the accumulated radioactivity was stronger and longer in the liver was than other organ.TPECT for tumour:liver ratio was 2.1?0.6. The efficacy for the treated group and the control group was respectively 61.9%(13/21) and 25.0%(5/20),the one-year cumulative survival rate of the treated group and the control group was also 61.9% and 25.0%.Conclusions: 125 I-anti-AFP via hepatic artery was able to concentrate electively in the tumour ,thereby bringing about a continuous internal irradiation for the tumour.This combined treatment is an effective method for PLC.

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