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1.
Adv Sci (Weinh) ; : e2401667, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627981

RESUMO

Constructing heterojunctions with vacancies has garnered substantial attention in the field of piezo-photocatalysis. However, the presence of interfacial vacancies can serve as charge-trapping sites, leading to the localization of electrons and hindering interfacial charge transfer. Herein, dual oxygen vacancies in the NiFe-layered double hydroxide and Bi2MoO6- x induced interfacial bonds have been designed for the piezo-photocatalytic N2 oxidation to NO3 -. Fortunately, it achieves sensational nitric acid production rates (7.23 mg g-1 h-1) in the absence of cocatalysts and sacrificial agents, which is 6.03 times of pure Bi2MoO6 that under ultrasound and light illumination. Theoretical and experimental results indicate that interfacial bonds act as "charge bridge" and "strain center" to break the carrier local effect and negative effects with piezocatalysis and photocatalysis for promoting exciton dissociation and charge transfer. Moreover, the strong electronic interaction of the interfacial bond induces internal reconstruction under ultrasound for promoting the local polarization and adsorption of N2, which accelerates the fracture of the N≡N bonds and reduces the activation energy of the reaction. The research not only establishes a novel approach for optimizing the combined effects of piezo-catalysis and photocatalysis, but also achieves equilibrium between the synergistic impacts of vacancies and heterojunctions.

2.
Analyst ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629585

RESUMO

Non-targeted analysis of high-resolution mass spectrometry (MS) can identify thousands of compounds, which also gives a huge challenge to their quantification. The aim of this study is to investigate the impact of mass spectrometry ionization efficiency on various compounds in food at different solvent ratios and to develop a predictive model for mass spectrometry ionization efficiency to enable non-targeted quantitative prediction of unknown compounds. This study covered 70 compounds in 14 different mobile phase ratio environments in positive ion mode to analyze the rules of the matrix effect. With the organic phase ratio from low to high, most compounds changed by 1.0 log units in log IE. The addition of formic acid enhanced the signal but also promoted the matrix effect, which often occurred in compounds with strong ionization capacity. It was speculated that the matrix effect was mainly in the form of competitive charge and charged droplet' gasification sites during MS detection. Subsequently, we present a log IE prediction method built using the COSMO-RS software and the artificial neural network (ANN) algorithm to address this difficulty and overcome the shortcomings of previous models, which always ignore the matrix effect. This model was developed following the principles of QSAR modeling recommended by the Organization for Economic Cooperation and Development (OECD). Furthermore, we validated this approach by predicting the log IE of 70 compounds, including those not involved in the log IE model development. The results presented demonstrate that the method we put forward has an excellent prediction accuracy for log IE (R2pred = 0.880), which means that it has the potential to predict the log IE of new compounds without authentic standards.

3.
Adv Mater ; : e2401772, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38634168

RESUMO

High-performance covalent organic framework (COF) fibers are demanded for an efficient capturing of blue osmotic power because of their excellent durability, simple integration, and large scalability. However, the scalable production of COF fibers is still very challenging due to the poor solubility and fragile structure of COFs. Herein, for the first time, we report that COF dispersions can be continuously processed into macroscopic, meter-long, and pure COF fibers using a wet spinning approach. The two presented COF fibers can be directly used for capturing of osmotic energy, avoiding the production of composite materials that require other additives and face challenges such as phase separation and environmental issues induced by the additives. A COF fiber exhibited power densities of 70.2 and 185.3 W m-2 at 50-fold and 500-fold salt gradients, respectively. These values outperform those of most reported systems, which indicates the high potential of COF fibers for capturing of blue osmotic energy. This article is protected by copyright. All rights reserved.

4.
Clin Microbiol Rev ; : e0016123, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634634

RESUMO

SUMMARYLincosamides constitute an important class of antibiotics used against a wide range of pathogens, including methicillin-resistant Staphylococcus aureus. However, due to the misuse of lincosamide and co-selection pressure, the resistance to lincosamide has become a serious concern. It is urgently needed to carefully understand the phenomenon and mechanism of lincosamide resistance to effectively prevent and control lincosamide resistance. To date, six mobile lincosamide resistance classes, including lnu, cfr, erm, vga, lsa, and sal, have been identified. These lincosamide resistance genes are frequently found on mobile genetic elements (MGEs), such as plasmids, transposons, integrative and conjugative elements, genomic islands, and prophages. Additionally, MGEs harbor the genes that confer resistance not only to antimicrobial agents of other classes but also to metals and biocides. The ultimate purpose of discovering and summarizing bacterial resistance is to prevent, control, and combat resistance effectively. This review highlights four promising strategies, including chemical modification of antibiotics, the development of antimicrobial peptides, the initiation of bacterial self-destruct program, and antimicrobial stewardship, to fight against resistance and safeguard global health.

5.
World J Gastroenterol ; 30(10): 1405-1419, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596488

RESUMO

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology. Alkaline sphingomyelinase (alk-SMase) is specifically expressed by intestinal epithelial cells, and has been reported to play an anti-inflammatory role. However, the underlying mechanism is still unclear. AIM: To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were administered 3% DSS drinking water, and disease activity index was determined to evaluate the status of colitis. Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran, and bacterial translocation was evaluated by measuring serum lipopolysaccharide. Intestinal epithelial cell ultrastructure was observed by electron microscopy. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA, respectively. Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels. RESULTS: Compared to wild-type (WT) mice, inflammation and intestinal permeability in alk-SMase knockout (KO) mice were more severe beginning 4 d after DSS induction. The mRNA and protein levels of intestinal barrier proteins, including zonula occludens-1, occludin, claudin-3, claudin-5, claudin-8, mucin 2, and secretory immunoglobulin A, were significantly reduced on 4 d after DSS treatment. Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells. Furthermore, by day 4, mitochondria appeared swollen and degenerated. Additionally, compared to WT mice, serum malondialdehyde levels in KO mice were higher, and the antioxidant capacity was significantly lower. The expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment. mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased. Finally, colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone, which is an Nrf2 activator. CONCLUSION: Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.


Assuntos
Colite Ulcerativa , Colite , Doença de Niemann-Pick Tipo A , Camundongos , Animais , Antioxidantes/uso terapêutico , Sulfato de Dextrana/toxicidade , Doença de Niemann-Pick Tipo A/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Colite/tratamento farmacológico , Colo , Colite Ulcerativa/tratamento farmacológico , Mucosa Intestinal , Anti-Inflamatórios/uso terapêutico , Camundongos Knockout , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
6.
Front Cell Infect Microbiol ; 14: 1372779, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596652

RESUMO

Aflatoxins (AFs) are produced by fungi such as Aspergillus flavus and A. parasiticus and are one of the most toxic mycotoxins found in agricultural products and food. Aflatoxin contamination, which requires the control of A. flavus, remains problematic because of the lack of effective strategies and the exploration of new compounds that can inhibit A. flavus growth and mycotoxin production is urgently required to alleviate potential deleterious effects. Acetohydroxy acid synthase (AHAS) and dihydroxy acid dehydratase are important enzymes in the biosynthetic pathways of branched-chain amino acids (BCAAs), including isoleucine, leucine, and valine. Enzymes involved in BCAA biosynthesis are present in bacteria, plants, and fungi, but not in mammals, and are therefore, attractive targets for antimicrobial and herbicide development. In this study, we characterized AflaILVB/G/I and AflaILVD, which encode the catalytic and regulatory subunits of AHAS and dihydroxy acid dehydratase, from the pathogenic fungus Aspergillus flavus. The AflaILVB/G/I and AflaILVD deletion mutant grew slower and produced smaller colonies than the wild-type strain when grown on glucose minimal medium, potato dextrose agar, and yeast extract medium for three days at 28°C, and disruption of AflaILVB/G/I caused a significant reduction in conidia production when grown on all kinds of media. Cellular stress assays determined that all strains were sensitive to H2O2. Importantly, the pathogenicity and aflatoxin production were affected when AflaILVB/G/I and AflaILVD were knocked out, particularly AflaILVB/G/I. A series of genes that encoded enzymes involved in aflatoxin synthesis were downregulated, meaning that the knockout of AflaILVB/G/I influenced aflatoxin synthesis in A. flavus strain WT. Collectively, our results demonstrate the potential value of antifungals targeting AflaILVB/G/I in A. flavus.


Assuntos
Aflatoxinas , Aspergillus flavus , Animais , Aspergillus flavus/genética , Virulência , Peróxido de Hidrogênio/metabolismo , Hidroliases , Mamíferos
7.
Surg Infect (Larchmt) ; 25(3): 247-252, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38588519

RESUMO

Background: The prevalence of community-onset infections of extended spectrum ß-lactamase (ESBL)-producing strains has increased globally, yet surveillance and resistance in patients with oral and maxillofacial surgery site infections is less investigated. Patients and Methods: A retrospective cohort study was performed to investigate risk factors and resistance of ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumonia (ESBL-KP) among community-onset patients with oral and maxillofacial surgery during January 2010 to December 2016. Demographic features, predisposing factors, clinical outcomes, and antibiotic agent costs were analyzed. Antimicrobial susceptibility testing of nine antimicrobial agents against ESBL-KP and ESBL-EC were measured. Results: Among 2,183 cultures from infection sites in patients with oral and maxillofacial surgery site (45 cases [2.06%]) were confirmed with community-onset ESBL-KP (24; 1.10%) or ESBL-EC (21; 0.96%) infection. Multivariable analysis showed the independent risk factors for ESBL-producing bacterial infection were prior history of hospitalization (adjusted odds ratio [aOR], 10.984; 95% confidence interval [CI], 5.965-59.879; p = 0.025) and malignant condition (aOR, 3.373; 95% CI 2.947-7.634; p = 0.024). Based on antimicrobial susceptibility testing, 57.8% ESBL-KP and ESBL-EC were found receiving inappropriate antimicrobial therapy, and antibiotic agent costs were higher than non-ESBL-producing bacterial infections ($493.8 ± $367.3 vs. $304.1 ± $334.7; p = 0.031). Conclusions: Infections caused by ESBL-KP and ESBL-EC among patients in sites with oral and maxillofacial surgery are associated with prior history of hospitalization and malignant conditions. Prompt detection and appropriate antibiotic administration for community-onset infections of ESBLs are necessary for such populations.


Assuntos
Infecções por Escherichia coli , Infecções por Klebsiella , Pneumonia , Humanos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Estudos Retrospectivos , beta-Lactamases , Escherichia coli , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fatores de Risco , Klebsiella , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia
8.
Exp Ther Med ; 27(5): 213, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590560

RESUMO

Steroid-induced osteonecrosis of the femoral head (ONFH) is a serious complication caused by long-term or excessive use of glucocorticoids. The present study aimed to ascertain the effects of tripartite motif-containing protein 21 (TRIM21) on the process of steroid-induced ONFH and its hidden action mechanism. TRIM21 expression in dexamethasone (Dex)-treated mouse MC3T3-E1 preosteoblast cells was examined using reverse transcription-quantitative PCR and western blotting. The Cell Counting Kit-8 (CCK-8) method and lactate dehydrogenase release assay were used to respectively measure cell viability and injury. Flow cytometry analysis was used to assay cell apoptosis. Caspase 3 activity was evaluated using a specific assay, while alkaline phosphatase and Alizarin red S staining were used to evaluate osteogenesis. 2,7-dichloro-dihydrofluorescein diacetate fluorescence probe was used to estimate reactive oxygen species generation. Specific assay kits were used to appraise oxidative stress levels. In addition, the expression of apoptosis-, osteogenic differentiation- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling-associated proteins was assessed using western blotting. In Nrf2 inhibitor (ML385)-pretreated MC3T3-E1 cells exposed to Dex, cell apoptosis, osteogenesis and oxidative stress were detected again as aforementioned. Results revealed that TRIM21 expression was raised in Dex-induced MC3T3-E1 cells and TRIM21 deletion improved the viability and osteogenic differentiation, whereas it hampered the oxidative stress and apoptosis in MC3T3-E1 cells with Dex induction. In addition, silencing of TRIM21 activated Keap1/Nrf2 signaling. Moreover, ML385 partially abrogated the effects of TRIM21 depletion on the oxidative stress, apoptosis and osteogenic differentiation in MC3T3-E1 cells exposed to Dex. In conclusion, TRIM21 silencing might activate Keap1/Nrf2 signaling to protect against steroid-induced ONFH.

9.
Br J Cancer ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594370

RESUMO

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.

10.
Adv Sci (Weinh) ; : e2308986, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588510

RESUMO

Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high-expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand-receptor pair. The inhibition of Mdk/Lrp1 activates the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune-cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for materials-designed strategies that target osteoimmune modulation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38591199

RESUMO

OBJECTIVE: To explore the mechanism of KLF15 on the biological activity and autophagy of gastric cancer cells based on the PI3K/Akt/mTOR signaling pathway. MATERIAL AND METHODS: The gastric cancer AGS cells were divided into the Con group, pcDNANC group, pcDNA-KLF15 group, LY294002 group and IGF-1 group. RT-PCR was used to detect the expression of KLF15 in human gastric mucosal cells and gastric cancer cells; MTT method to detect cell proliferation; Transwell method to detect cell invasion; flow cytometry to detect cell apoptosis; Western blotting to detect PI3K, Akt, mTOR in cells, LC3, Beclin1, p62 protein expression.P<0.05 was used to indicate statistical significance. RESULTS: Compared with the human gastric mucosal cell line GES-1 cells, the expression of KLF15 in human gastric cancer cell lines MKN-28, MFC, SCG-7901 and AGS cells was significantly decreased, And the expression of KLF15 in AGS cells, was the lowest (P=0.006). Compared with the Con group, The expression of KLF15 in the cells of the PCDNA-KLF15 group was significantly increased (P=0.018); There was no significant difference in the expression of KLF15 between the Con group and the PCDNA-NC group (P=0.225). Compared with the Con group, the proliferation and invasion abilities of the cells in the pcDNA-KLF15 group were significantly reduced, And the apoptosis ability was significantly increased (P=0.019). The ratio of LC3II/LC31 and the expression of Beclin1 Protein in the control group were significantly higher than those in the Con group (P=0.017). CONCLUSION: Overexpression of KLF15 can inhibit the proliferation and invasion of Gastric cancer cells and promote cell apoptosis and autophagy, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR signaling pathway.

12.
Ergonomics ; : 1-20, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592045

RESUMO

Studies have demonstrated two-stage takeover systems' feasibility and advantages. However, existing cognitive models mainly focus on simulating drivers' performance in single-stage takeover systems, with limited insights into cognitive modelling of effects of monitoring requests (MRs) within two-stage takeover systems. This study constructed a cognitive computational model for two-stage takeover systems based on queueing network-adaptive control of thought rational (QN-ACTR) architecture. Our model aims to capture variations in drivers' attention allocation and takeover performance resulting from different MR experiences. Five components, representing distinct cognitive processes, were designed to closely align with drivers' behavioural patterns. This model was validated through an experiment using metrics such as percentage time in road-centre and takeover time. Results revealed significant concordance between the model predictions and experimental data, with R-squared ≥ 0.76, RMSE ≤ 0.41, and MAPE ≤ 15%. The findings of this work extended beyond the two-stage takeover system investigation to include human factor modelling.


To provide insights into modelling the effects of monitoring requests in two-stage takeover systems, a cognitive computational model was developed to simulate driver behaviour. An experiment was conducted to validate the model's predictive performance. The quantisation relation between warning signals and driver performance can be calculated through the proposed model.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38592427

RESUMO

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.

14.
Arch Pharm Res ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592582

RESUMO

Sarcopenia is a multifactorial condition characterized by loss of muscle mass. It poses significant health risks in older adults worldwide. Both pharmacological and non-pharmacological approaches are reported to address this disease. Certain dietary patterns, such as adequate energy intake and essential amino acids, have shown positive outcomes in preserving muscle function. Various medications, including myostatin inhibitors, growth hormones, and activin type II receptor inhibitors, have been evaluated for their effectiveness in managing sarcopenia. However, it is important to consider the variable efficacy and potential side effects associated with these treatments. There are currently no drugs approved by the Food and Drug Administration for sarcopenia. The ongoing research aims to develop more effective strategies in the future. Our review of research on disease mechanisms and drug development will be a valuable contribution to future research endeavors.

15.
Shanghai Kou Qiang Yi Xue ; 33(1): 85-89, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38583031

RESUMO

PURPOSE: To study the relationship between the expression of prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) and the osteogenic activity and oxygen level of alveolar bone. METHODS: The alveolar bones of 56 patients with chronic periodontitis who received dental treatment from March 2021 to March 2023 were collected as the experimental (periodontitis) group, and the healthy alveolar bones of 53 patients who received dental treatment during the same period were selected as the control group. The osteoblasts were cultured by tissue block culture, and modified Kaplow's alkaline phosphatase (ALP) staining was used to identify the cells. COX-2, PGE2 and osteoclastogenesis inhibitory factor (OPG) receptor activator of nuclear factor-κb ligand (RANKL) and other indicators were determined by ELISA. PGE2, COX-2, OPG, internal oxygen level, ALP, RANKL and their correlation were compared between the two groups. Statistical analysis was performed with SPSS 27.0 software package. RESULTS: PGE2, COX-2 and RANKL in periodontitis group were significantly higher than those in the control group, but OPG, internal oxygen level and ALP were significantly lower than those in the control group (P<0.05). PGE2 and COX2 were highly positively correlated with OPG, internal oxygen level and ALP, but were highly positively correlated with RANKL(P<0.05). CONCLUSIONS: The expression of PGE2 and COX-2 is highly negatively correlated with ALP and oxygen levels. Clinical treatment may consider increasing oxygen levels, increasing oxygen partial pressure, and regulating ALP levels by drugs, so as to change the inflammatory condition of periodontitis or other dental diseases.


Assuntos
Dinoprostona , Periodontite , Humanos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Dinoprostona/farmacologia , Osteoblastos/metabolismo , Osteogênese , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo
16.
Front Immunol ; 15: 1331609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558816

RESUMO

In the genesis and progression of cardiovascular diseases involving both innate and adaptive immune responses, inflammation plays a pivotal and dual role. Studies in experimental animals indicate that certain immune responses are protective, while others exacerbate the disease. T-helper (Th) 1 cell immune responses are recognized as key drivers of inflammatory progression in cardiovascular diseases. Consequently, the CD4+CD25+FOXP3+ regulatory T cells (Tregs) are gaining increasing attention for their roles in inflammation and immune regulation. Given the critical role of Tregs in maintaining immune-inflammatory balance and homeostasis, abnormalities in their generation or function might lead to aberrant immune responses, thereby initiating pathological changes. Numerous preclinical studies and clinical trials have unveiled the central role of Tregs in cardiovascular diseases, such as atherosclerosis. Here, we review the roles and mechanisms of Treg subsets in cardiovascular conditions like atherosclerosis, hypertension, myocardial infarction and remodeling, myocarditis, dilated cardiomyopathy, and heart failure. While the precise molecular mechanisms of Tregs in cardiac protection remain elusive, therapeutic strategies targeting Tregs present a promising new direction for the prevention and treatment of cardiovascular diseases.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Infarto do Miocárdio , Animais , Linfócitos T Reguladores , Doenças Cardiovasculares/terapia , Inflamação
17.
Toxicon ; : 107709, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615996

RESUMO

Deoxynivalenol is a widespread feed contaminant that leads to vomit, which results in serious symptom such as increased intestinal permeability and even intestinal mucosal necrosis. Recent studies have reported the role of quercetin in alleviating deoxynivalenol-induced intestinal injury; however, the mechanisms and targets remain unclear. Thus, we aimed to identify the mechanisms of action by using a combination of network pharmacology and molecular docking. We identified 151 quercetin targets, 235 deoxynivalenol targets and 47 porcine intestinal injury targets by searching compound database and PubMed database, among which there were two common targets. The PPI network showed that the key proteins involved are NQO1 and PPAR-γ. The PPI network showed that the key proteins involved were NQO1 and PPARG. GO analysis found that genes were enriched primarily in response to oxidative stress. The PPI network showed that the key proteins involved are NQO1 and PPAR-γ. The genes are enriched primarily in response to oxidative stress. KEGG analysis showed enrichment of the HIF, reactive oxygen species and other signaling pathways. The molecular docking results indicated key binding activity between NQO1-quercetin and PPAR-γ-quercetin. By using network pharmacology, we have revealed the potential molecular mechanisms by which quercetin alleviates deoxynivalenol-induced porcine intestinal injury, which lays the foundation for the development of drugs to treat deoxynivalenol-induced intestinal injury in pigs.

18.
Orthop Surg ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616159

RESUMO

BACKGROUND: Minimally invasive surgery (MIS) such as minimally invasive chevron osteotomy and Akin osteotomy (MICA) has become popular in the treatment of hallux valgus. However, how to correct three-dimensional deformities in hallux valgus effectively and simply in MICA is still difficult. Special equipment is required in MICA as has been reported before. It is meaningful and necessary to reduce the reliance on special equipment in MICA. METHODS: From January 2021 to July 2022, patients with mild or moderate hallux valgus were treated with a joy-stick assistant three-dimensional modified technique (Joy-stick 3D technique) of MIS. VAS, AOFAS Hallux MTP-IP scores, hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were measured pre- and postoperatively at the last follow-up of at least 6 months. Scores and radiologic angles were compared using paired sample t-test. RESULTS: A total of 36 cases were included. HVA, IMA, and DMAA were (22.3 ± 6.1)°, (14.0 ± 3.2)°, and (8.9 ± 3.2)° preoperatively, and decreased to (7.0 ± 1.8)°, (3.7 ± 1.0)°, and (3.3 ± 1.1)° postoperatively. VAS decreased from 4.3 ± 1.7 to 0.7 ± 0.7. AOFAS Hallux MTP-IP scores improved from 68.6 ± 7.6 to 92.9 ± 6.1. Comparing mild and moderate cases, though HVA, IMA, and DMAA were significantly different preoperatively, the angles became statistically similar after surgery. CONCLUSIONS: A joy-stick assistant three-dimensional modified technique is proposed to control the three-dimensional position of the metatarsal head and to reduce dependence on special tools. Mild and moderate hallux valgus deformities are effectively corrected using Joy-stick 3D technique.

19.
Am J Gastroenterol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619136

RESUMO

OBJECTIVES: Fully covered self-expandable metal stents (FCSEMS) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the two groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared to the control group (16.7% vs. 30.0%, p = 0.030). The proximal and distal migration rates were similar in the two groups (2.2% vs. 5.6%, p=0.205; 14.4% vs. 22.2%, p=0.070). Notably, none of the patients (0/8) who received two or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the two groups. CONCLUSIONS: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.

20.
Int Immunopharmacol ; 132: 111780, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38603853

RESUMO

BACKGROUND: Glycopeptide antibiotic vancomycin is a bactericidal antibiotic available for the infection to Staphylococcus aureus (SA), however, SA has a strong adaptive capacity and thereby acquires resistance to vancomycin. This study aims to illuminate the possible molecular mechanism of vancomycin resistance of SA based on the 16S rRNA sequencing data and microarray profiling data. METHODS: 16S rRNA sequencing data of control samples and urinary tract infection samples were retrieved from the EMBL-EBI (European Molecular Biology Laboratory - European Bioinformatics Institute) database. Correlation of gut flora and clinical indicators was evaluated. The possible targets regulated by SA were predicted by microarray profiling and subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. CXCL10 gene knockout and overexpression were introduced to evaluate the effect of CXCL10 on the virulence of SA and the resistance to vancomycin. SA strains were co-cultured with urethral epithelial cells in vitro. The presence of SA virulence factors was detected using PCR. Biofilm formation of SA strains was assessed using the microtiter plate method. Furthermore, the antibiotic sensitivity of SA strains was evaluated through vancomycin testing. RESULTS: Gut flora and its species abundance had significant difference between urinary tract infection and control samples. SA was significantly differentially expressed in urinary tract infection samples. Resistance of SA to vancomycin mainly linked to the D-alanine metabolism pathway. SA may participate in the occurrence of urinary tract infection by upregulating CXCL10. In addition, CXCL10 mainly affected the SA resistance to vancomycin through the TLR signaling pathway. In vitro experimental results further confirmed that the overexpression of CXCL10 in SA increased SA virulence and decreased its susceptibility to vancomycin. In vitro experimental validation demonstrated that the knockout of CXCL10 in urethral epithelial cells enhanced the sensitivity of Staphylococcus aureus (SA) to vancomycin. CONCLUSION: SA upregulates the expression of CXCL10 in urethral epithelial cells, thereby activating the TLR signaling pathway and promoting resistance to glycopeptide antibiotics in SA.

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