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1.
Bioorg Med Chem Lett ; : 129822, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38823728

ABSTRACT

The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.

2.
Adv Sci (Weinh) ; : e2400023, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828688

ABSTRACT

The factors driving glioma progression remain poorly understood. Here, the epigenetic regulator TRIM24 is identified as a driver of glioma progression, where TRIM24 overexpression promotes HRasV12 anaplastic astrocytoma (AA) progression into epithelioid GBM (Ep-GBM)-like tumors. Co-transfection of TRIM24 with HRasV12 also induces Ep-GBM-like transformation of human neural stem cells (hNSCs) with tumor protein p53 gene (TP53) knockdown. Furthermore, TRIM24 is highly expressed in clinical Ep-GBM specimens. Using single-cell RNA-sequencing (scRNA-Seq), the authors show that TRIM24 overexpression impacts both intratumoral heterogeneity and the tumor microenvironment. Mechanically, HRasV12 activates phosphorylated adaptor for RNA export (PHAX) and upregulates U3 small nucleolar RNAs (U3 snoRNAs) to recruit Ku-dependent DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Overexpressed TRIM24 is also recruited by PHAX to U3 snoRNAs, thereby facilitating DNA-PKcs phosphorylation of TRIM24 at S767/768 residues. Phosphorylated TRIM24 induces epigenome and transcription factor network reprogramming and promotes Ep-GBM-like transformation. Targeting DNA-PKcs with the small molecule inhibitor NU7441 synergizes with temozolomide to reduce Ep-GBM tumorigenicity and prolong animal survival. These findings provide new insights into the epigenetic regulation of Ep-GBM-like transformation and suggest a potential therapeutic strategy for patients with Ep-GBM.

3.
Adv Clin Exp Med ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860714

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on clinical outcomes. Anion gap (AG)/albumin corrected anion gap (ACAG) are used to assess acid-base balance status and help identify the severity of metabolic acidosis. OBJECTIVES: To explore the association of AG and ACAG with the risk of AKI in AIS patients admitted to the intensive care unit (ICU). MATERIAL AND METHODS: Data of AIS patients in this retrospective cohort study were extracted from the electronic ICU (eICU) databases (2014-2015). The outcome was the occurrence of AKI after ICU admission. The covariates included demographic data, vital signs, comorbidities, laboratory parameters, and medication use. The association of AG and ACAG levels with AKI risk in AIS patients was evaluated using univariate and multivariate logistic regression models with odds ratios (ORs) and 95% confidence intervals (95% CIs). The predictive performance of AG and ACAG for the risk of AKI in AIS patients was assessed with the area under the curve (AUC). To further explore the association of AG and ACAG levels with AKI risk, subgroup analyses were performed according to comorbidities. RESULTS: Of the 1,260 AIS patients, 546 (43%) developed AKI. Elevated AG (OR = 1.73, 95% CI: 1.32-2.29) and ACAG (OR = 1.57, 95% CI: 1.21-2.04) were associated with the risk of AKI in AIS patients. The AUC of ACAG was superior to AG for predicting the risk of AKI (0.581 vs 0.558; p = 0.024). Elevated ACAG levels were associated with the risk of AKI in AIS patients without ischemic heart disease (OR = 1.60, 95% CI: 1.19-2.15), diabetes (OR = 1.58, 95% CI: 1.19-2.10) and hypertension (OR = 1.69, 95% CI: 1.24-2.30). CONCLUSIONS: Albumin corrected anion gap was a better predictor than AG for AKI risk in AIS patients, which may help clinicians identify high-risk patients for AKI.

5.
Vet Res Forum ; 15(4): 171-179, 2024.
Article in English | MEDLINE | ID: mdl-38770198

ABSTRACT

Rhipicephalus sanguineus, a repulsive obligate blood feeder, is a three-host tick inflicting tremendous damage. Blood-sucking initiates tick-pathogen-host interactions along with alterations in the expression levels of numerous bioactive ingredients. Key molecules regulating blood meals were identified using the transcriptomic approach. A total number of 744 transcripts showed statistically significantly differential expression including 309 significantly upregulated transcripts and 435 significantly downregulated transcripts in semiengorged female ticks compared to unfed ticks, all collected in 2021. The top 10 differentially upregulated transcripts with explicit functional annotations included turripeptide OL55-like protein, valine tRNA ligase-like protein and ice-structuring glycoprotein-like protein. The top 10 differentially down-regulated transcripts were uncharacterized proteins. Gene Ontology (GO) enrichment analysis revealed four associated terms in the cellular component category and 16 in the molecular function category among the top 20 terms. Differentially expressed genes (DEGs) were enriched in GO terms ID 0000323 (lytic vacuole) and ID 0005773 (vacuole). The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included metabolism, cellular processes, organismal systems and human diseases. The DEGs were enriched in the KEGG term ID: ko-04142 (lysosome pathway) associated with intracellular digestion in the tick midgut epithelium. Molecular markers annotated via comparative transcriptomic profiling were expected to be candidate markers for the purpose of tick control.

7.
World J Gastrointest Oncol ; 16(5): 1787-1795, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38764817

ABSTRACT

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

9.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2197-2209, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812235

ABSTRACT

This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.


Subject(s)
Acute Lung Injury , Drugs, Chinese Herbal , Molecular Docking Simulation , Network Pharmacology , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Mice , Rats , Male , Protein Interaction Maps , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Rats, Sprague-Dawley , Humans
10.
Comput Biol Med ; 176: 108498, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38744011

ABSTRACT

With advancements in science and technology, the depth of human research on COVID-19 is increasing, making the investigation of medical images a focal point. Image segmentation, a crucial step preceding image processing, holds significance in the realm of medical image analysis. Traditional threshold image segmentation proves to be less efficient, posing challenges in selecting an appropriate threshold value. In response to these issues, this paper introduces Inner-based multi-strategy particle swarm optimization (IPSOsono) for conducting numerical experiments and enhancing threshold image segmentation in COVID-19 medical images. A novel dynamic oscillatory weight, derived from the PSO variant for single-objective numerical optimization (PSOsono) is incorporated. Simultaneously, the historical optimal positions of individuals in the particle swarm undergo random updates, diminishing the likelihood of algorithm stagnation and local optima. Moreover, an inner selection learning mechanism is proposed in the update of optimal positions, dynamically refining the global optimal solution. In the CEC 2013 benchmark test, PSOsono demonstrates a certain advantage in optimization capability compared to algorithms proposed in recent years, proving the effectiveness and feasibility of PSOsono. In the Minimum Cross Entropy threshold segmentation experiments for COVID-19, PSOsono exhibits a more prominent segmentation capability compared to other algorithms, showing good generalization across 6 CT images and further validating the practicality of the algorithm.


Subject(s)
Algorithms , COVID-19 , SARS-CoV-2 , COVID-19/diagnostic imaging , Humans , Image Processing, Computer-Assisted/methods , Machine Learning
11.
J Autism Dev Disord ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819702

ABSTRACT

PURPOSE: School is an important developmental setting for children. Adverse childhood experiences (ACEs) are linked to overall lower educational attainment and are more prevalent in children with Autism Spectrum Disorder (ASD) than in their neurotypical peers. The aim of this study is to test the association between ACEs and school outcomes among autistic children and whether mental health conditions explain this association. METHODS: We combined 2016-2021 data from the National Surveys of Children's Health for children, ages 6-17, identified by parents as having ASD (N = 4,997), to examine the relationship between ACEs and school outcomes (grade progression, school attendance, and engagement). We analyzed depression and anxiety variables to investigate the extent to which mental health can explain the relationships between ACEs and school outcomes. RESULTS: ACEs were significantly associated with school outcomes. With increased ACEs, autistic children experienced a significant decrease in the odds of school attendance, grade progression and school engagement (p < .05). Furthermore, although depression and anxiety symptoms were significantly associated with school outcomes, they cannot explain away the enduring, strong relationship between ACEs and level of grade progression, engagement, and school success index. CONCLUSION: Our findings suggest ACEs predict school success among autistic children, with mental health conditions appearing to mediate the relationship between ACEs and key factors in school success. Efforts should be made to proactively identify and address the impact of ACEs and associated mental health conditions among autistic students.

12.
RSC Med Chem ; 15(4): 1198-1209, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38665835

ABSTRACT

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

13.
Bioorg Med Chem ; 105: 117716, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38608329

ABSTRACT

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.


Subject(s)
Cell Survival , Cyclohexylamines , Drug Design , Ferroptosis , Human Umbilical Vein Endothelial Cells , Piperazines , Humans , Ferroptosis/drug effects , Piperazines/pharmacology , Piperazines/chemical synthesis , Piperazines/chemistry , Human Umbilical Vein Endothelial Cells/drug effects , Structure-Activity Relationship , Cyclohexylamines/pharmacology , Cyclohexylamines/chemistry , Cyclohexylamines/chemical synthesis , Cell Survival/drug effects , Molecular Structure , Phenylenediamines/pharmacology , Phenylenediamines/chemistry , Phenylenediamines/chemical synthesis , Dose-Response Relationship, Drug , Reactive Oxygen Species/metabolism , Ferrous Compounds/pharmacology , Ferrous Compounds/chemistry , Ferrous Compounds/chemical synthesis , Membrane Potential, Mitochondrial/drug effects
14.
Zhen Ci Yan Jiu ; 49(4): 434-440, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38649213

ABSTRACT

There are the differences in the location of some acupoints between textbooks Meridians and Acupoints and Acupuncture and Moxibustion. Both of the textbooks are in the category of the "14th Five-Year Plan". The differences in acupoint location have brought some confusion for students, full-time teachers and researchers in the field of traditional Chinese medicine. In the paper, based on GB/T 12346-2021: Nomenclature and Location of Meridian Points, published in2021, and in reference with GB/T 12346-2006: Nomenclature and Location of Acupuncture Points, published in 2006, the discrepancy in the acupoint location was systematically collated in the aspects of the expression style and layout, text expression and potential difference of location between these two textbooks, published by China Press of Traditional Chinese Medicine, People's Medical Publishing House and China Science Publishing. Based on the historical evolution and the academic controversy of acupoint positioning, the reasons of the differences in acupoint location were analyzed, the potential influences on the teaching, examination, competition and research of Chinese medicine acupuncture were explored, and the suggestions for solution were proposed.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Meridians , Moxibustion , Humans , Moxibustion/history , China , Acupuncture/education , Acupuncture/history , Medicine, Chinese Traditional
15.
Chin Med Sci J ; 39(1): 74-78, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38623049

ABSTRACT

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.


Subject(s)
Dermatitis, Atopic , Macular Edema , Retinal Detachment , Retinal Vasculitis , Male , Humans , Young Adult , Adult , Retinal Detachment/etiology , Retinal Detachment/surgery , Retinal Detachment/diagnosis , Dermatitis, Atopic/complications , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/surgery , Retinal Vasculitis/drug therapy , Retinal Vasculitis/complications , Retinal Vasculitis/surgery , Macular Edema/etiology , Macular Edema/complications , Scleral Buckling/adverse effects , Retrospective Studies
16.
J Clin Invest ; 134(11)2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662454

ABSTRACT

Widespread alterations in RNA alternative splicing (AS) have been identified in adult gliomas. However, their regulatory mechanism, biological significance, and therapeutic potential remain largely elusive. Here, using a computational approach with both bulk and single-cell RNA-Seq, we uncover a prognostic AS signature linked with neural developmental hierarchies. Using advanced iPSC glioma models driven by glioma driver mutations, we show that this AS signature could be enhanced by EGFRvIII and inhibited by in situ IDH1 mutation. Functional validations of 2 isoform switching events in CERS5 and MPZL1 show regulations of sphingolipid metabolism and SHP2 signaling, respectively. Analysis of upstream RNA binding proteins reveals PTBP1 as a key regulator of the AS signature where targeting of PTBP1 suppresses tumor growth and promotes the expression of a neuron marker TUJ1 in glioma stem-like cells. Overall, our data highlights the role of AS in affecting glioma malignancy and heterogeneity and its potential as a therapeutic vulnerability for treating adult gliomas.


Subject(s)
Alternative Splicing , Glioma , Polypyrimidine Tract-Binding Protein , Glioma/genetics , Glioma/pathology , Glioma/metabolism , Glioma/therapy , Humans , Polypyrimidine Tract-Binding Protein/genetics , Polypyrimidine Tract-Binding Protein/metabolism , Animals , Mice , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/therapy , Adult , Induced Pluripotent Stem Cells/metabolism , Cell Line, Tumor , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism
17.
Toxicol Lett ; 396: 81-93, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38670245

ABSTRACT

PURPOSE: Uremic cardiomyopathy (UCM) is the leading cause of chronic kidney disease (CKD) related mortality. Uremic toxins including indoxyl sulfate (IS) play important role during the progression of UCM. This study was to explore the underlying mechanism of IS related myocardial injury. METHODS: UCM rat model was established through five-sixths nephrectomy to evaluate its effects on blood pressure, cardiac impairment, and histological changes using echocardiography and histological analysis. Additionally, IS was administered to neonatal rat cardiomyocytes (NRCMs) and the human cardiomyocyte cell line AC16. DHE staining and peroxide-sensitive dye 2',7'-dichlorofluorescein diacetate (H2DCFDA) was conducted to assess the reactive oxygen species (ROS) production. Cardiomyocyte hypertrophy was estimated using wheat germ agglutinin (WGA) staining and immunofluorescence. Aryl hydrocarbon receptor (AhR) translocation was observed by immunofluorescence. The activation of AhR was evaluated by immunoblotting of cytochrome P450 1 s (CYP1s) and quantitative real-time PCR (RT-PCR) analysis of AHRR and PTGS2. Additionally, the pro-oxidative and pro-hypertrophic effects were evaluated using the AhR inhibitor CH-223191, the CYP1s inhibitor Alizarin and the ROS scavenger N-Acetylcysteine (NAC). RESULTS: UCM rat model was successfully established, and cardiac hypertrophy, accompanied by increased blood pressure, and myocardial fibrosis. Further research confirmed the activation of the AhR pathway in UCM rats including AhR translocation and downstream protein CYP1s expression, accompanied with increasing ROS production detected by DHE staining. In vitro experiment demonstrated a translocation of AhR triggered by IS, leading to significant increase of downstream gene expression. Subsequently study indicated a close relationship between the production of ROS and the activation of AhR/CYP1s, which was effectively blocked by applying AhR inhibitor, CYP1s inhibitor and siRNA against AhR. Moreover, the inhibition of AhR/CYP1s/ROS pathway collectively blocked the pro-hypertrophic effect of IS-mediated cardiomyopathy. CONCLUSION: This study provides evidence that the AhR/CYP1s pathway is activated in UCM rats, and this activation is correlated with the uremic toxin IS. In vitro studies indicate that IS can stimulate the AhR translocation in cardiomyocyte, triggering to the production of intracellular ROS via CYP1s. This process leads to prolonged oxidative stress stimulation and thus contributes to the progression of uremic toxin-mediated cardiomyopathy.


Subject(s)
Cardiomyopathies , Indican , Myocytes, Cardiac , Rats, Sprague-Dawley , Reactive Oxygen Species , Receptors, Aryl Hydrocarbon , Signal Transduction , Uremia , Animals , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/genetics , Reactive Oxygen Species/metabolism , Uremia/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Indican/toxicity , Humans , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Rats , Male , Cell Line , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Oxidative Stress , Disease Models, Animal , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology
18.
Front Immunol ; 15: 1379853, 2024.
Article in English | MEDLINE | ID: mdl-38650937

ABSTRACT

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.


Subject(s)
Phenotype , Animals , Mice , Tumor Microenvironment/immunology , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Macrophages/immunology , Cell Proliferation , Cell Line, Tumor , Mice, Inbred C57BL , Apoptosis , Phagocytosis , Cell Movement/immunology
19.
Materials (Basel) ; 17(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38612214

ABSTRACT

The present investigation endeavors to explore the influence of rare earth elements on the strength and plasticity characteristics of low-carbon microalloyed steel under tensile loading conditions. The findings from the conducted tensile tests indicate that the incorporation of rare earths leads to a notable enhancement in the yield strength, ultimate tensile strength, and ductility properties of the steel. A comparative analysis of the microstructures reveals that the presence of rare earths significantly refines and optimizes the microstructure of the microalloyed steel. This optimization is manifested through a reduction in grain size, diminution of inclusion sizes, and a concomitant rise in their number density. Moreover, the addition of rare earths is observed to foster an increase in the volumetric fraction of carbides within the steel matrix. These multifaceted microstructural alterations collectively contribute to a substantial strengthening of the microalloyed steel. Furthermore, it is elucidated that the synergistic interaction between rare earth elements and both carbon (C) and niobium (Nb) in the steel matrix augments the extent of the Lüders strain region during the tensile deformation of specimens. This phenomenon is accompanied by the effective modification of inclusions by the rare earths, which serves to mitigate stress concentrations at the interfaces between the inclusions and the surrounding matrix. This article systematically evaluates the modification mechanism of rare earth microalloying, which provides a basis for broadening the application of rare earth microalloying in microalloyed steel.

20.
Risk Manag Healthc Policy ; 17: 843-853, 2024.
Article in English | MEDLINE | ID: mdl-38617594

ABSTRACT

Purpose: The purpose of the study was to determine the status of spiritual needs and influencing factors of postoperative breast cancer (BC) women undergoing chemotherapy. Participants and Methods: This study is a cross-sectional study. A total of 173 participants completed a general information questionnaire and a Chinese version of the Spiritual Needs Scale at the Guangxi Medical University Cancer Hospital. Data were collected by purposive sampling from December 2022 to April 2023. Data were analyzed by descriptive statistics, independent t-test, ANOVA, non-parametric test, and logistic regression analysis. Results: The spiritual needs of postoperative BC women undergoing chemotherapy were at a high level (84.20 ± 12.86). The need for "hope and peace" was considered paramount and the need for a "relationship with transcendence" was considered the least important. Significant differences were found in the following: spiritual needs total score (P=0.040) and "hope and peace" (P=0.021) in education level; "love and connection" in disease stage (P=0.021); "meaning and purpose" in education level (P=0.013), household income (P=0.012), and payment method (P=0.015); "relationship with transcendence" in religion (P<0.001); and "acceptance of dying" in marital status (P=0.023). The level of education was the influencing factor of spiritual needs (OR=1.50, P=0.005), especially for "hope and peace" (OR=1.50, P=0.012). Conclusion: The spiritual need of postoperative BC Chinese women undergoing chemotherapy is at a high level and should receive more attention. In clinical work, nurses should fully assess the spiritual needs of patients and meet their specific needs. Results may help nurses to develop targeted and comprehensive spiritual intervention strategies according to the characteristics of patients.

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