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1.
ACS Nano ; 18(34): 23104-23116, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39146318

RÉSUMÉ

Degradation and interference of the nucleic acid probes in complex biological environments like cytoplasm or body fluid can cause obvious false-positive signals and inefficient bioregulation in biosensing and biomedicine. To solve this problem, here, we proposed a universal strategy, termed L-DNA assembly mirror-image box-based environment resistance (L-AMBER), to protect nucleic acid probes from degradation and maintain their responsive activity in complex biological environments. Strand displacement reaction (SDR), aptamer, or DNAzyme-based D-DNA probes were encapsulated into an L-DNA box by using an L-D-L block DNA carrier strand to construct different kinds of L-AMBER probes. We proved that the L-DNA box could effectively protect the encapsulated D-DNA probes by shielding the interference of complex biological environments and only allowing small target molecules to enter for recognition. Compared with the D-AMBER probes, the L-AMBER probes can realize DNase I-assisted amplification detection of biological samples, low false-positive bioimaging, and highly efficient miRNA silence in living cells. Therefore, L-AMBER provided a universal and effective strategy for enhancing the resistance to environmental interference of nucleic acid probes in biosensing and biomedicine applications.


Sujet(s)
ADN , Humains , ADN/composition chimique , ADN/génétique , Techniques de biocapteur , microARN/génétique , microARN/analyse , Deoxyribonuclease I/métabolisme , ADN catalytique/composition chimique , ADN catalytique/métabolisme , Sondes d'acide nucléique/composition chimique , Cellules HeLa , Sondes d'ADN/composition chimique
2.
J Colloid Interface Sci ; 677(Pt B): 101-110, 2024 Aug 12.
Article de Anglais | MEDLINE | ID: mdl-39137559

RÉSUMÉ

Sodium-selenium (Na-Se) batteries are promising energy storage systems with high energy density, high safety, and low cost. However, the huge volume change of selenium, the dissolution shuttle of polyselenides, and low selenium loading need to be solved. Herein, Cu nanoparticles decorated MXene nanosheets composite (MXene/Cu) are synthesized by etching Ti3AlC2 using a molten salt etching strategy. The Se-loaded MXene/Cu (Se@MXene/Cu) electrode delivers superior electrochemical performance even with a high Se loading of ∼74.3 wt%, owing to the synergistic effect of the two-dimensional (2D) confined structure and catalytic role of the unique MXene/Cu host. Specifically, the obtained electrode provides a reversible capacity of 587.3 mAh/g at 0.2 A/g, a discharge capacity as high as 511.3 mAh/g at a high rate of 50 A/g, and still maintains a capacity of 471.9 mAh/g even after 5000 cycles based on the mass of Se@MXene/Cu. With such excellent electrochemical kinetic properties, this study highlights the importance of designing various MXene-based composites with synergistic effects of 2D confined structure and Cu catalytic center for the development of high-performance alkali metal-chalcogen battery systems.

3.
Plant Cell ; 2024 Aug 21.
Article de Anglais | MEDLINE | ID: mdl-39167833

RÉSUMÉ

Autoluminescent plants have been genetically modified to express the fungal bioluminescence pathway (FBP). However, a bottleneck in precursor production has limited the brightness of these luminescent plants. Here, we demonstrate the effectiveness of utilizing a computational model to guide a multiplex five-gene-silencing strategy by an artificial microRNA array to enhance caffeic acid and hispidin levels in plants. By combining loss-of-function-directed metabolic flux with a tyrosine-derived caffeic acid pathway, we achieved substantially enhanced bioluminescence levels. We successfully generated eFBP2 plants that emit considerably brighter bioluminescence for naked-eye reading by integrating all validated DNA modules. Our analysis revealed that the luminous energy conversion efficiency of the eFBP2 plants is currently very low, suggesting that luminescence intensity can be improved in future iterations. These findings highlight the potential to enhance plant luminescence through the integration of biological and information technologies.

4.
Biosensors (Basel) ; 14(5)2024 May 08.
Article de Anglais | MEDLINE | ID: mdl-38785710

RÉSUMÉ

The rise of DNA nanotechnology has driven the development of DNA-based molecular machines, which are capable of performing specific operations and tasks at the nanoscale. Benefitting from the programmability of DNA molecules and the predictability of DNA hybridization and strand displacement, DNA-based molecular machines can be designed with various structures and dynamic behaviors and have been implemented for wide applications in the field of biosensing due to their unique advantages. This review summarizes the reported controlling mechanisms of DNA-based molecular machines and introduces biosensing applications of DNA-based molecular machines in amplified detection, multiplex detection, real-time monitoring, spatial recognition detection, and single-molecule detection of biomarkers. The challenges and future directions of DNA-based molecular machines in biosensing are also discussed.


Sujet(s)
Techniques de biocapteur , ADN , Nanotechnologie , Hybridation d'acides nucléiques , Humains
5.
J Colloid Interface Sci ; 663: 801-809, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38442521

RÉSUMÉ

Sodium-selenium (Na-Se) batteries have gained attention due to their high energy density and power density, resulting from the liquid-liquid reaction at the interface in the dimethoxyethane electrolyte. Nevertheless, the pronounced shuttle effect of polyselenides causes low coulomb efficiency and inadequate cycling stability for Na-Se batteries. Herein, the iron nanoparticles surface modified accordion-like Ti3C2Tx MXene (MXene/Fe) synthesized via the molten salt etching is utilized as the host of Se species for high-performance Na-Se battery cathode. Benefiting from the layered structure and chemical adsorption of accordion-like MXene, the shuttle effect of the cathode is effectively inhibited. Simultaneously, electrochemical kinetics is boosted due to the catalytic effect of Fe nanoparticles, which facilitate the transformation of polyselenide from long-chain to short-chain, contributing to pseudocapacitive capacity. Consequently, the Se-based cathode delivers a steady capacity of 575.0 mA h g-1 at 0.2 A/g, and even a high capacity of 500 mAh/g at 50 A/g based on the mass of Se@MXene/Fe electrode, indicating the ultrafast Na+ ion storage. Most notably, this structure demonstrated remarkable long-term cycling stability for 5000 cycles with a high capacity retention of 97.4 %. The electrochemical energy storage mechanism is further revealed by in situ Raman. Herein, the confinement-catalysis structure shines light on inhibiting shuttling and facilitating ultrafast ion storage.

6.
Gut Microbes ; 16(1): 2310894, 2024.
Article de Anglais | MEDLINE | ID: mdl-38312103

RÉSUMÉ

Gut microbiota and related metabolites are both crucial factors that significantly influence how individuals with Crohn's disease respond to immunotherapy. However, little is known about the interplay among gut microbiota, metabolites, Crohn's disease, and the response to anti-α4ß7-integrin in current studies. Our research utilized 2,4,6-trinitrobenzene sulfonic acid to induce colitis based on the humanized immune system mouse model and employed a combination of whole-genome shotgun metagenomics and non-targeted metabolomics to investigate immunotherapy responses. Additionally, clinical cases with Crohn's disease initiating anti-α4ß7-integrin therapy were evaluated comprehensively. Particularly, 16S-rDNA gene high-throughput sequencing and targeted bile acid metabolomics were conducted at weeks 0, 14, and 54. We found that anti-α4ß7-integrin therapy has shown significant potential for mitigating disease phenotypes in remission-achieving colitis mice. Microbial profiles demonstrated that not only microbial composition but also microbially encoded metabolic pathways could predict immunotherapy responses. Metabonomic signatures revealed that bile acid metabolism alteration, especially elevated secondary bile acids, was a determinant of immunotherapy responses. Especially, the remission mice significantly enriched the proportion of the beneficial Lactobacillus and Clostridium genera, which were correlated with increased gastrointestinal levels of BAs involving lithocholic acid and deoxycholic acid. Moreover, most of the omics features observed in colitis mice were replicated in clinical cases. Notably, anti-α4ß7 integrin provided sustained therapeutic benefits in clinical remitters during follow-up, and long-lasting remission was linked to persistent changes in the microbial-related bile acids. In conclusion, gut microbiota-mediated bile acid metabolism alteration could play a crucial role in regulating immunotherapy responses to anti-α4ß7-integrin in Crohn's disease. Therefore, the identification of prognostic microbial signals facilitates the advancement of targeted probiotics that activate anti-inflammatory bile acid metabolic pathways, thereby improving immunotherapy responses. The integrated multi-omics established in our research provide valuable insights into potential mechanisms that impact treatment responses in complex diseases.


Sujet(s)
Colite , Maladie de Crohn , Microbiome gastro-intestinal , Animaux , Souris , Maladie de Crohn/traitement médicamenteux , Multi-omique , Intégrines/génétique , Intégrines/usage thérapeutique , Colite/induit chimiquement , Colite/thérapie , Acides et sels biliaires/usage thérapeutique , Immunothérapie
7.
Rev Esp Enferm Dig ; 2024 Jan 11.
Article de Anglais | MEDLINE | ID: mdl-38205697

RÉSUMÉ

Background Pyoderma gangrenosum (PG) is a rare extraintestinal manifestation of inflammatory bowel disease. In recent years, the use of biologics in PG has been on the rise and has shown promising results. The surgical treatment of PG remains a topic of debate, with limited reports on the use of postoperative biologic therapy. Case reprt: This case report describes a 52-year-old woman who presented with multiple skin ulcers, pus discharge, and bloody diarrhea. The patient was diagnosed with PG with ulcerative colitis based on medical history, ulcer appearance, histopathology, treatment response, and the presence of ulcerative colitis. Surgical intervention was performed to repair the ulcers and amputate the fourth finger and fourth toe of both feet. Additionally, infliximab induction therapy was initiated two weeks after the surgery. The patient's intestinal symptoms demonstrated improvement, and after 10 months of treatment, the lesions were completely healed with no recurrence of skin ulcers. Conclusions This case report highlights a rare instance of successful treatment for PG with ulcerative colitis through a combination of surgery and postoperative infliximab.

8.
Transl Oncol ; 40: 101842, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38035446

RÉSUMÉ

OBJECTIVE: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases. METHODS: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC. RESULTS: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression. CONCLUSION: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

10.
Gut Microbes ; 15(1): 2232143, 2023.
Article de Anglais | MEDLINE | ID: mdl-37431863

RÉSUMÉ

The gut microbiota and bile acid metabolism are key determinants of the response of inflammatory bowel disease to biologic therapy. However, the molecular mechanisms underlying the interactions between the response to anti-α4ß7-integrin therapy and the gut microbiota and bile acid metabolism remain unknown. In this research, we investigated the role of gut microbiota-related bile acid metabolism on the response to anti-α4ß7-integrin therapy in a humanized immune system mouse model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid. We found that anti-α4ß7-integrin significantly mitigated intestinal inflammation, pathological symptoms, and gut barrier disruption in remission-achieving colitis mice. Whole-genome shotgun metagenomic sequencing demonstrated that employing baseline microbiome profiles to predict remission and the treatment response was a promising strategy. Antibiotic-mediated gut microbiota depletion and fecal microbiome transplantation revealed that the baseline gut microbiota contained common microbes with anti-inflammatory effects and reduced mucosal barrier damage, improving the treatment response. Targeted metabolomics analysis illustrated that bile acids associated with microbial diversity were involved in colitis remission. Furthermore, the activation effects of the microbiome and bile acids on FXR and TGR5 were evaluated in colitis mice and Caco-2 cells. The findings revealed that the production of gastrointestinal bile acids, particularly CDCA and LCA, further directly promoted the stimulation of FXR and TGR5, significantly improving gut barrier function and suppressing the inflammatory process. Taken together, gut microbiota-related bile acid metabolism-FXR/TGR5 axis may be a potential mechanism for impacting the response to anti-α4ß7-integrin in experimental colitis. Thus, our research provides novel insights into the treatment response in inflammatory bowel disease.


Sujet(s)
Colite , Microbiome gastro-intestinal , Maladies inflammatoires intestinales , Animaux , Souris , Humains , Cellules Caco-2 , Colite/induit chimiquement , Colite/traitement médicamenteux , Acides et sels biliaires , Intégrines
12.
World J Gastroenterol ; 29(22): 3422-3439, 2023 Jun 14.
Article de Anglais | MEDLINE | ID: mdl-37389234

RÉSUMÉ

BACKGROUND: Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes, which can progress to cirrhosis. AIM: To evaluate the effect and mechanism of action annexin (Anx)A1 in liver fibrosis and how this could be targeted therapeutically. METHODS: CCl4 (20%) and active N-terminal peptide of AnxA1 (Ac2-26) and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2) were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice, and to detect expression of inflammatory factors, collagen deposition, and the role of the Wnt/ß-catenin pathway in hepatic fibrosis. RESULTS: Compared with the control group, AnxA1, transforming growth factor (TGF)-ß1, interleukin (IL)-1ß and IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased, which promoted collagen deposition and expression of α-smooth muscle actin (α-SMA), collagen type I and connective tissue growth factor (CTGF), and increased progressively with time. CCl4 induced an increase in TGF-ß1, IL-1ß and IL-6 in liver tissue of AnxA1 knockout mice, and the degree of liver inflammation and fibrosis and expression of α-SMA, collagen I and CTGF were significantly increased compared with in wild-type mice. After treatment with Ac2-26, expression of liver inflammatory factors, degree of collagen deposition and expression of a-SMA, collagen I and CTGF were decreased compared with before treatment. Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26. AnxA1 downregulated expression of the Wnt/ß-catenin pathway in CCl4-induced hepatic fibrosis. In vitro, lipopolysaccharide (LPS) induced hepatocyte and hepatic stellate cell (HSC) expression of AnxA1. Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation, decreased expression of α-SMA, collagen I and CTGF in HSCs, and inhibited expression of the Wnt/ß-catenin pathway after HSC activation. These therapeutic effects were inhibited by Boc2. CONCLUSION: AnxA1 inhibited liver fibrosis in mice, and its mechanism may be related to inhibition of HSC Wnt/ß-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.


Sujet(s)
Annexine A1 , bêta-Caténine , Animaux , Souris , Annexine A1/génétique , Cellules étoilées du foie , Interleukine-6 , Lipopolysaccharides , Macrophages , Cirrhose du foie/induit chimiquement , Collagène de type I
13.
Int Immunopharmacol ; 119: 110137, 2023 Jun.
Article de Anglais | MEDLINE | ID: mdl-37126984

RÉSUMÉ

Extracellular vesicles (EVs) exhibit pivotal functions in cancer via intercellular communication through shuttling microRNA (miRNA) and protein. Therefore, we aim to elucidate the function of EVs containing miR-143-3p derived from M2 macrophages in colorectal cancer (CRC). EVs derived from M2 macrophages were isolated and characterized. Expression changes in miR-143-3p were calculated in the EVs. The effects of M2 macrophage-derived EV carrying miR-143-3p on cell biological processes and in vivo tumorigenic ability concerning ZC3H12A were examined. EVs derived from M2 macrophages could stimulate the aggressive tumor biology of CRC cells. Meanwhile, in vivo results showed that M2 macrophage-derived EVs facilitated tumor growth and epithelial-mesenchymal transition. M2 macrophage-secreted EVs could transfer miR-143-3p to CRC cells, in which miR-143-3p bound to the 3'UTR of ZC3H12A and inhibited its expression, leading to elevation of the expression of transcription factor C/EBPß. Overall, M2 macrophage-derived EV miR-143-3p inhibits ZC3H12A gene and increases C/EBPß expression to facilitate the development of CRC, which provides novel targets for the molecular treatment of CRC.


Sujet(s)
Tumeurs colorectales , Vésicules extracellulaires , microARN , Humains , Macrophages/métabolisme , microARN/génétique , microARN/métabolisme , Vésicules extracellulaires/métabolisme , Transition épithélio-mésenchymateuse , Tumeurs colorectales/anatomopathologie , Ribonucléases , Facteurs de transcription/métabolisme
14.
Int J Colorectal Dis ; 38(1): 82, 2023 Mar 27.
Article de Anglais | MEDLINE | ID: mdl-36971914

RÉSUMÉ

PURPOSE: There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of combination therapy and infliximab (IFX) monotherapy in CD patients. METHODS: We identified randomized controlled trials (RCTs) in CD patients who were given IFX-containing combination therapy versus IFX monotherapy. Induction and maintenance of clinical remission were the efficacy outcomes, while adverse events were the safety outcomes. The surface under cumulative ranking (SUCRA) probabilities was used to assess ranking in the network meta-analysis. RESULTS: In total, 15 RCTs with 1586 CD patients were included in this study. There was no statistical difference between different combination therapies in induction and maintenance of remission. In terms of inducing clinical remission, IFX + EN (SUCRA: 0.91) ranked highest; in terms of maintaining clinical remission, IFX + AZA (SUCRA: 0.85) ranked highest. There was no treatment that was significantly safer than the others. In terms of any adverse events, serious adverse events, serious infections, and infusion/injection-site reactions, IFX + AZA (SUCRA: 0.36, 0.12, 0.19, and 0.24) was ranked lowest for all risks; while IFX + MTX (SUCRA: 0.34, 0.06, 0.13, 0.08, 0.34, and 0.08) was rated lowest for risk of abdominal pain, arthralgia, headache, nausea, pyrexia, and upper respiratory tract infection. CONCLUSION: Indirect comparisons suggested that efficacy and safety of different combination treatments are comparable in CD patients. For maintenance therapies, IFX + AZA was ranked highest for clinical remission and lowest for adverse events. Further head-to-head trials are required.


Sujet(s)
Maladie de Crohn , Humains , Infliximab/effets indésirables , Maladie de Crohn/traitement médicamenteux , Immunosuppresseurs/usage thérapeutique , Méta-analyse en réseau , Induction de rémission
15.
ChemSusChem ; 16(9): e202202212, 2023 May 05.
Article de Anglais | MEDLINE | ID: mdl-36693800

RÉSUMÉ

Photoelectrocatalysis (PEC) is regarded as a promising and sustainable process for removal of organic contaminants from wastewater. Meanwhile, enzymatic catalysis also provides an effective way to carry out polluted environment remediation under mild conditions. In this study, a biophotoelectrocatalytic (BPEC) system is designed to remove 4-nitrophenol (4-NP) based on a combination of PEC and enzymatic catalysis. The developed BPEC system is constructed with a Ag3 PO4 /BiVO4 photoanode and a horseradish peroxidase (HRP)-loaded carbon cloth (CC) cathode. On the photoanode, the construction of a direct Z-scheme Ag3 PO4 /BiVO4 heterojunction enhanced the separation efficiency of photogenerated carriers, which promoted the PEC degradation of 4-NP under visible light irradiation. After HRP was immobilized on the cathode, the degradation efficiency of 4-NP reached 97.1 % after 60 min PEC treatment. The result could be ascribed to the HRP-catalyzed oxidation reaction via in situ-generated H2 O2 from the CC cathode during the PEC process. Moreover, the possible degradation pathways of 4-NP in such a BPEC system are also discussed.

16.
Angew Chem Int Ed Engl ; 62(10): e202215387, 2023 03 01.
Article de Anglais | MEDLINE | ID: mdl-36479802

RÉSUMÉ

Cell-specific aptamers offer a powerful tool to study membrane receptors at the single-molecule level. Most target receptors of aptamers are highly expressed on the cell surface, but difficult to analyze in situ because of dense distribution and fast velocity. Therefore, we herein propose a random sampling-based analysis strategy termed ligand dilution analysis (LDA) for easily implemented aptamer-based receptor study. Receptor density on the cell surface can be calculated based on a regression model. By using a synergistic ligand dilution design, colocalization and differentiation of aptamer and monoclonal antibody (mAb) binding on a single receptor can be realized. Once this is accomplished, precise binding site and detailed aptamer-receptor binding mode can be further determined using molecular docking and molecular dynamics simulation. The ligand dilution strategy also sets the stage for an aptamer-based dynamics analysis of two- and three-dimensional motion and fluctuation of highly expressed receptors on the live cell membrane.


Sujet(s)
Aptamères nucléotidiques , Ligands , Simulation de docking moléculaire , Aptamères nucléotidiques/composition chimique , Sites de fixation , Liaison aux protéines , Technique SELEX
17.
Foods ; 11(8)2022 Apr 10.
Article de Anglais | MEDLINE | ID: mdl-35454677

RÉSUMÉ

Highland barley has a different composition and structure to other crops. It has higher contents of total polyphenol (TPC), total flavonoid (TFC) and ß-glucan, which can be supplemented to improve the nutrition of wheat-flour-based food. In this study, the flours of three different grain-colored highland barley varieties Beiqing 6 (BQ), Dulihuang (DLH), and Heilaoya (HLY), were added to Jimai60 (JM, a wheat variety with medium gluten) wheat flour at different substitution levels to investigate their effects on the unextractable polymeric protein (UPP) content, micro-structure, rheological properties and mixing properties of dough, and the color, texture, flavor, and in vitro digestion of Chinese steam bread (CSB). The results showed that the moderate substitution of highland barley (20%) increased the UPP%, optimized the micro-structure of gluten, and improved its rheological properties by increasing dough viscoelasticity. The CSBs made from the composite flours exhibited a similar specific volume, cohesiveness, springiness and resilience to wheat CSB, while the firmness of composite CSBs (particularly JM-HLY-20) was delayed during storage. Importantly, the addition of highland barley increased the contents of TPC, TFC and ß-glucan, but decreased the in vitro starch digestibility of CSBs. A sensory evaluation showed that JM-HLY CSB was the most preferable. Taken together, highland barley can be used as a fine supplement to food products, with health-promoting properties.

18.
Expert Rev Mol Diagn ; 22(8): i-xiii, 2022 08.
Article de Anglais | MEDLINE | ID: mdl-34877908

RÉSUMÉ

Statement of RetractionWe, the Editors and Publisher of the journal Expert Review of Molecular Diagnostics, have retracted the following article:Sen Hong, Zhenkun Yan, YuMei Song, MiaoMiao Bi & Shiquan Li. Down-regulation of lncRNA FEZF1-AS1 mediates regulatory T cell differentiation and further blocks immune escape in colon cancer. Expert Review of Molecular Diagnostics. 2021. DOI: 10.1080/14737159.2022.2012157Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.

19.
Int J Gen Med ; 14: 9163-9172, 2021.
Article de Anglais | MEDLINE | ID: mdl-34880655

RÉSUMÉ

OBJECTIVE: To analyze the correlation between site rs962917 of the MYO9B gene and inflammatory bowel disease (IBD) in the Guangxi Zhuang nationality population. METHODS: The intestinal mucosa tissue of 153 IBD subjects (Han and Zhuang patients only) in the Guangxi Zhuang autonomous region comprised the case group, and the intestinal mucosa tissue of 155 healthy subjects (Han and Zhuang patients only) in the same region represented the control group. Deoxyribonucleic acid was extracted from the intestinal mucosa tissue of each experimental group, and the MYO9B gene-target fragment containing the single nucleotide polymorphism (SNP) site rs962917 was designed. Finally, polymerase chain reaction products were obtained by amplification, analyzed, and compared using the sequencing results. RESULTS: The results indicated that the genotype frequency of the MYO9B SNP site rs962917 between Crohn's disease (CD) and control groups of Zhuang and Han participants differed significantly (P < 0.05). Furthermore, the genotype frequency of MYO9B site rs962917 differed significantly between the Zhuang and Han population groups (P < 0.05). CONCLUSION: Site rs962917 of the MYO9B gene is related to CD susceptibility and incidence among the Guangxi Zhuang population.

20.
Front Pharmacol ; 12: 734040, 2021.
Article de Anglais | MEDLINE | ID: mdl-34707499

RÉSUMÉ

Objective: To investigate the immunological mechanism of bone marrow-derived mesenchymal stem cells (BM-MSCs) in inflammatory bowel disease (IBD). Methods: Mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were intraperitoneally injected with phosphate-buffered saline, BM-MSCs, BM-MSCs with tumor necrosis factor-induced protein 6 (Tnfaip6) knockdown mediated by RNA interference recombinant adenovirus, and BM-MSCs-infected with control adenovirus or recombinant mouse Tnfaip6. The disease activity index, weight loss, and histological scores were recorded. Serum levels of Tnfaip6 and pro- and anti-inflammatory cytokines, including interleukin (IL)-21, tumor necrosis factor-alpha (TNF-α), IL-10 were measured by enzyme-linked immunosorbent assay. The relative expression levels of these cytokines, B-cell lymphoma 6 (BCL-6) and fork-like transcription factor p3 (Foxp3) in the colon were determined by real-time quantitative PCR (RT-qPCR). BCL-6 and Foxp3 are the master regulators of follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr), respectively. The infiltration of Tfh and Tfr in mesenteric lymph nodes (MLNs) and spleens was analyzed by flow cytometry. Results: Compared to the normal control group, the expression levels of BCL-6 and IL-21 in the colon, Tfh infiltration, and ratios of Tfh/Tfr in the MLNs and spleen, and the serum concentrations of IL-21 and TNF-α increased significantly in the colitis model group (p < 0.05). Intraperitoneal injection of BM-MSCs or Tnfaip6 ameliorated weight loss and clinical and histological severity of colitis, downregulated the expression of BCL-6, IL-21, and TNF-α, upregulated the expression of Foxp3, IL-10, and Tnfaip6 (p < 0.05), increased Tfr and reduced the infiltration of Tfh in the MLNs and spleen, and downregulated the Tfh/Tfr ratio (p < 0.05). On the other hand, BM-MSCs lost the therapeutic effect and immune regulatory functions on Tfh and Tfr after Tnfaip6 knockdown. Conclusion: Tfh increase in the inflamed colon, Tfh decrease and Tfr increase during the colitis remission phase, and the imbalance of the Tfh/Tfr ratio is closely related to the progression of IBD. Tnfaip6 secreted by BM-MSCs alleviates IBD by inhibiting Tfh differentiation, promoting Tfr differentiation, and improving the imbalance of Tfh/Tfr in mice.

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