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1.
JMIR Med Inform ; 12: e62757, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38838306

ABSTRACT

[This corrects the article DOI: 10.2196/44892.].

3.
Article in English | MEDLINE | ID: mdl-38843427

ABSTRACT

Objective: To study the intervention effects of the health education and health promotion (PRECEDE-PROCEED) model on the health behaviors and quality of life of obese children and their parents. Methods: 524 patients who attended our pediatric obesity clinic from January to December 2021 were selected and divided into two groups: the control group (n = 262) and the test group (n = 262). The control group was guided by conventional weight reduction instruction, while the test group implemented the PRECEDE-PROCEED model. Based on this model, interventions were developed following the 9 links of the model, with tendency factors, contributing factors, and reinforcing factors as the core and 6 aspects of health behaviors were focused upon, and were followed up for 12 months. A home-made questionnaire scale was used to assess the subjects at their initial visit and one year after the intervention. Results: After the intervention, the awareness rate of obesity-related knowledge, support rate of attitude toward improving childhood obesity, awareness rate of disease harm caused by obesity, and formation rate of controlling childhood obesity behavior had significantly improved among the parents of the test group compared to the control group, with significant differences between the two groups (P < .05). Conclusion: The PRECEDE-PROCEED model can transform the way parents of obese children apply health education at home, improving health behaviors and quality of life.

5.
Am J Transl Res ; 16(4): 1219-1227, 2024.
Article in English | MEDLINE | ID: mdl-38715832

ABSTRACT

OBJECTIVE: We aimed to assess the impact of integrated nursing and psychological intervention on pain intensity and patient satisfaction in individuals with urinary calculi. METHODS: This retrospective study included 94 urological patients from the Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, between January 2020 and June 2022. Participants were divided into a control group (n=48), receiving routine nursing and psychological intervention, and a study group (n=46), receiving integrated nursing and psychological intervention. We compared pain intensity, pain relief rate, patient satisfaction, Numeric Rating Scale (NRS) score, Pittsburgh Sleep Quality Index (PSQI) score, Self-rating Depression Scale (SDS) score, Self-rating Anxiety Scale (SAS) score, and quality of life scores between the groups. RESULTS: The study group had shorter hospital stays and lower hospitalization costs than the control group (both P < 0.05). Pain relief and satisfaction rates were higher in the study group (both P < 0.05). Post-intervention, both groups showed significant reductions in NRS, PSQI, SDS, and SAS scores, with greater reductions in the study group (all P < 0.05). Quality of life scores increased in both groups, more so in the SG (P < 0.05). The study group also had fewer adverse events (P < 0.05). Both groups showed decreased serum creatinine and blood urea nitrogen levels post-intervention, with a more significant decline in the study group (P < 0.05). Education, marital status, and occupation were major factors influencing outcomes in urinary calculi patients. CONCLUSION: Integrated nursing and psychological intervention significantly alleviates pain, improves emotional well-being, enhances sleep quality, increases overall life quality, and contributes to high patient satisfaction among urinary calculi patients.

6.
Clin Exp Med ; 24(1): 112, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795162

ABSTRACT

Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Cytochrome P450 Family 4 , Extracellular Traps , Liver Neoplasms , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Liver Neoplasms/secondary , Liver Neoplasms/genetics , Cytochrome P450 Family 4/genetics , Cytochrome P450 Family 4/metabolism , Prognosis , Extracellular Traps/metabolism , Biomarkers, Tumor/genetics , Nomograms , Gene Expression Profiling , Male , Female , Gene Expression Regulation, Neoplastic , Neutrophils/metabolism
7.
Theor Appl Genet ; 137(6): 123, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722407

ABSTRACT

KEY MESSAGE: BrBCAT1 encoding a branched-chain amino acid aminotransferase was responsible for the glossy trait, which was verified by allelic mutants in Chinese cabbage. The glossy characteristic, thanks to the epicuticular wax crystal deficiency, is an excellent commodity character for leafy vegetables. Herein, two allelic glossy green mutants, wdm11 and wdm12, were isolated from an ethyl methane sulfonate (EMS)-mutagenized population of Chinese cabbage, and the mutant phenotype was recessive inherited. Cryo-SEM detected that epicuticular wax crystal in the mutant leaves was virtually absent. MutMap and Kompetitive allele-specific PCR analyses demonstrated that BraA06g006950.3C (BrBCAT1), homologous to AtBCAT1, encoding a branched-chain amino acid aminotransferase was the candidate gene. A SNP (G to A) on the fourth exon of BrBCAT1 in wdm11 caused the 233rd amino acid to change from glycine (G) to aspartic acid (D). A SNP (G to A) on the second exon of BrBCAT1 in wdm12 led to the 112th amino acid change from glycine (G) to arginine (R). Both of the allelic mutants had genetic structural variation in the candidate gene, which indicated that the mutant phenotype was triggered by the BrBCAT1 mutation. The expression levels of BrBCAT1 and genes related to fatty acid chain extension were decreased significantly in the mutant compared to the wild-type, which might result in epicuticular wax crystal deficiency in the mutants. Our findings proved that the mutation of BrBCAT1 induced the glossy phenotype and provided a valuable gene resource for commodity character improvement in Chinese cabbage.


Subject(s)
Alleles , Brassica , Mutation , Phenotype , Waxes , Brassica/genetics , Waxes/chemistry , Waxes/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Polymorphism, Single Nucleotide , Plant Leaves/genetics , Transaminases/genetics
8.
Int J Pharm ; 659: 124202, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38705247

ABSTRACT

Photodynamic therapy (PDT) shows great potential in precision tumor treatment. However, its efficacy is inhibited by the antioxidant defense capacities of tumor cells. To address this challenge, a near-infrared light-controlled nanosystem (UCNPs@mSiO2@Azo@ZnPc&BBM, PB@UA) was developed using emission-switchable upconversion nanoparticles (UCNPs) to independently and precisely control the release of berbamine (BBM) and activation of photosensitizer for enhanced PDT in deep tissues. Firstly, BBM release was triggered by exciting PB@UA at 980 nm. The BBM could inhibit the activities of antioxidant enzymes and disrupt calcium ion regulation, making the tumor cells more susceptible to ROS-induced cell death in the following PDT treatment. The PDT was initiated by irradiating the photosensitizers of ZnPc on PB@UA at 808 nm and achieved a tumor inhibition rate of 80.91 % in vivo, which is significantly higher than that of unique PDT (31.78 %) or BBM (11.29 %) treatment and demonstrates the potential of our strategy for improved cancer treatment.

9.
Heliyon ; 10(7): e28490, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38590858

ABSTRACT

Background: High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and aggressive histological subtype of epithelial ovarian cancer. Around 80% of individuals will experience a recurrence within five years because of resistance to chemotherapy, despite initially responding well to platinum-based treatment. Biomarkers associated with chemoresistance are desperately needed in clinical practice. Methods: We jointly analyzed the transcriptomic profiles of single-cell and bulk datasets of HGSOC to identify cell types associated with chemoresistance. Copy number variation (CNV) inference was performed to identify malignant cells. We subsequently analyzed the expression of candidate biomarkers and their relationship with patients' prognosis. The enrichment analysis and potential biological function of candidate biomarkers were explored. Then, we validated the candidate biomarker using in vitro experiments. Results: We identified 8871 malignant epithelial cells in a single-cell RNA sequencing dataset, of which 861 cells were associated with chemoresistance. Among these malignant epithelial cells, FBXO2 (F-box protein 2) is highly expressed in cells related to chemoresistance. Moreover, FBXO2 expression was found to be higher in epithelial cells from chemoresistance samples compared to those from chemosensitivity samples in a separate single-cell RNA sequencing dataset. Patients exhibiting elevated levels of FBXO2 experienced poorer outcomes in terms of both overall survival (OS) and progression-free survival (PFS). FBXO2 could impact chemoresistance by influencing the PI3K-Akt signaling pathway, focal adhesion, and ECM-receptor interactions and regulating tumorigenesis. The 50% maximum inhibitory concentration (IC50) of cisplatin decreased in A2780 and SKOV3 ovarian carcinoma cell lines with silenced FBXO2 during an in vitro experiment. Conclusions: We determined that FBXO2 is a potential biomarker linked to chemoresistance in HGSOC by combining single-cell RNA-seq and bulk RNA-seq dataset. Our results suggest that FBXO2 could serve as a valuable prognostic marker and potential target for drug development in HGSOC.

10.
Medicine (Baltimore) ; 103(16): e37796, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38640283

ABSTRACT

BACKGROUND: Asthma ranks among the most prevalent non-communicable diseases worldwide. Previous studies have elucidated the significant role of the immune system in its pathophysiology. Nevertheless, the immune-related mechanisms underlying asthma are complex and still inadequately understood. Thus, our objective was to investigate novel key biomarkers and immune infiltration characteristics associated with asthma by employing integrated bioinformatics tools. METHODS: In this study, we conducted a weighted gene co-expression network analysis (WGCNA) to identify key modules and genes potentially implicated in asthma. Functional annotation of these key modules and genes was carried out through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, we constructed a protein-protein interaction (PPI) network using the STRING database to identify 10 hub genes. Furthermore, we evaluated the relative proportion of immune cells in bronchial epithelial cell samples from 20 healthy individuals and 88 asthmatic patients using CIBERSORT. Finally, we validated the hub genes and explored their correlation with immune infiltration. RESULTS: Furthermore, 20 gene expression modules and 10 hub genes were identified herein. Among them, complement component 3 (C3), prostaglandin I2 receptor (PTGIR), parathyroid hormone-like hormone (PTHLH), and C-X3-C motif chemokine ligand 1 (CX3CL1) were closely correlated with the infiltration of immune cells. They may be novel candidate biomarkers or therapeutic targets for asthma. Furthermore, B cells memory, and plasma cells might play an important role in immune cell infiltration after asthma. CONCLUSIONS: C3, PTGIR, CX3CL1, and PTHLH have important clinical diagnostic values and are correlated with infiltration of multiple immune cell types in asthma. These hub genes, B cells memory, and plasma cells may become important biological targets for therapeutic asthma drug screening and drug design.


Subject(s)
Asthma , Epithelial Cells , Humans , Asthma/genetics , Biomarkers , Computational Biology , Databases, Factual , Gene Regulatory Networks
11.
Nanoscale ; 16(17): 8479-8494, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38590261

ABSTRACT

Catalytic generation of toxic hydroxyl radicals (˙OH) from hydrogen peroxide (H2O2) is an effective strategy for tumor treatment in chemodynamic therapy (CDT). However, the intrinsic features of the microenvironment in solid tumors, characterized by limited H2O2 and overexpressed glutathione (GSH), severely impede the accumulation of intracellular ˙OH, posing significant challenges. To circumvent these critical issues, in this work, a CaO2-based multifunctional nanocomposite with a surface coating of Cu2+ and L-buthionine sulfoximine (BSO) (named CaO2@Cu-BSO) is designed for enhanced CDT. Taking advantage of the weakly acidic environment of the tumor, the nanocomposite gradually disintegrates, and the exposed CaO2 nanoparticles subsequently decompose to produce H2O2, alleviating the insufficient supply of endogenous H2O2 in the tumor microenvironment (TME). Furthermore, Cu2+ detached from the surface of CaO2 is reduced by H2O2 and GSH to Cu+ and ROS. Then, Cu+ catalyzes H2O2 to generate highly cytotoxic ˙OH and Cu2+, forming a cyclic catalysis effect for effective CDT. Meanwhile, GSH is depleted by Cu2+ ions to eliminate possible ˙OH scavenging. In addition, the decomposition of CaO2 by TME releases a large amount of free Ca2+, resulting in the accumulation and overload of Ca2+ and mitochondrial damage in tumor cells, further improving CDT efficacy and accelerating tumor apoptosis. Besides, BSO, a molecular inhibitor, decreases GSH production by blocking γ-glutamyl cysteine synthetase. Together, this strategy allows for enhanced CDT efficiency via a ROS storm generation strategy in tumor therapy. The experimental results confirm and demonstrate the satisfactory tumor inhibition effect both in vitro and in vivo.


Subject(s)
Calcium , Copper , Glutathione , Hydrogen Peroxide , Nanocomposites , Tumor Microenvironment , Nanocomposites/chemistry , Nanocomposites/therapeutic use , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Glutathione/metabolism , Glutathione/chemistry , Animals , Humans , Mice , Calcium/metabolism , Calcium/chemistry , Copper/chemistry , Copper/pharmacology , Tumor Microenvironment/drug effects , Cell Line, Tumor , Buthionine Sulfoximine/pharmacology , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Reactive Oxygen Species/metabolism , Hydroxyl Radical/metabolism , Hydroxyl Radical/chemistry , Mice, Inbred BALB C
12.
Toxicology ; 504: 153796, 2024 May.
Article in English | MEDLINE | ID: mdl-38582279

ABSTRACT

As a broad-spectrum and efficient insecticide, beta-Cypermethrin (ß-CYP) poses a health risk to pregnancy. It matters the mechanisms of maternal exposure to ß-CYP for impacting reproductive health. The placenta, a transient organ pivotal for maternal-fetal communication during pregnancy, plays a crucial role in embryonic development. The effect of ß-CYP exposure on the placenta and its underlying molecular mechanisms remain obscure. The objective of this study was to investigate the effect of ß-CYP exposure on placental development and the function of trophoblast, as well as the underlying mechanisms through CD-1 mouse model (1, 10, 20 mg/kg.bw) and in vitro HTR-8/SVneo cell model (12.5, 25, 50, 100 µM). We found slower weight gain and reduced uterine wet weight in pregnant mice with maternal exposure to ß-CYP during pregnancy, as well as adverse pregnancy outcomes such as uterine bleeding and embryo resorption. The abnormal placental development in response to ß-CYP was noticed, including imbalanced placental structure and disrupted labyrinthine vascular development. Trophoblasts, pivotal in placental development and vascular remodeling, displayed abnormal differentiation under ß-CYP exposure. This aberration was characterized by thickened trophoblast layers in the labyrinthine zone, accompanied by mitochondrial and endoplasmic reticulum swelling within trophoblasts. Further researches on human chorionic trophoblast cell lines revealed that ß-CYP exposure induced apoptosis in HTR-8/SVneo cells. This induction resulted in a notable decrease in migration and invasion abilities, coupled with oxidative stress and the inhibition of the Notch signaling pathway. N-acetylcysteine (an antioxidant) partially restored the impaired Notch signaling pathway in HTR-8/SVneo cells, and mitigated cellular functional damage attributed to ß-CYP exposure. Collectively, exposure to ß-CYP induced oxidative stress and then led to inhibition of the Notch signaling pathway and dysfunction of trophoblast cells, ultimately resulted in abnormal placenta and pregnancy. These findings indicate Reactive Oxygen Species as potential intervention targets to mitigate ß-CYP toxicity. The comprehensive elucidation contributes to our understanding of ß-CYP biosafety and offers an experimental basis for preventing and managing its reproductive toxicity.


Subject(s)
Insecticides , Oxidative Stress , Pyrethrins , Trophoblasts , Pyrethrins/toxicity , Female , Pregnancy , Trophoblasts/drug effects , Trophoblasts/pathology , Trophoblasts/metabolism , Oxidative Stress/drug effects , Animals , Mice , Insecticides/toxicity , Humans , Maternal Exposure/adverse effects , Placentation/drug effects , Cell Line , Placenta/drug effects , Placenta/pathology , Placenta/metabolism , Apoptosis/drug effects
13.
Neural Netw ; 174: 106222, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38442490

ABSTRACT

Recent years have witnessed increasing interest in the few-shot knowledge graph completion due to its potential to augment the coverage of few-shot relations in knowledge graphs. Existing methods often use the one-hop neighbors of the entity to enhance its embedding and match the query instance and support set at the instance level. However, such methods cannot handle inter-neighbor interaction, local entity matching and the varying significance of feature dimensions. To bridge this gap, we propose the Multi-Level Attention-enhanced matching Network (MuLAN) for few-shot knowledge graph completion. In MuLAN, a multi-head self-attention neighbor encoder is designed to capture the inter-neighbor interaction and learn the entity embeddings. Then, entity-level attention and instance-level attention are responsible for matching the query instance and support set from the local and global perspectives, respectively, while feature-level attention is utilized to calculate the weights of the feature dimensions. Furthermore, we design a consistency constraint to ensure the support instance embeddings are close to each other. Extensive experiments based on two well-known datasets (i.e., NELL-One and Wiki-One) demonstrate significant advantages of MuLAN over 11 state-of-the-art competitors. Compared to the best-performing baseline, MuLAN achieves 14.5% higher MRR and 13.3% higher Hits@K on average.


Subject(s)
Knowledge , Pattern Recognition, Automated , Learning
14.
Oncol Rep ; 51(4)2024 04.
Article in English | MEDLINE | ID: mdl-38456540

ABSTRACT

Cancer metastasis is the primary cause of cancer deaths. Metastasis involves the spread of cancer cells from the primary tumors to other body parts, commonly through lymphatic and vascular pathways. Key aspects include the high mutation rate and the capability of metastatic cells to form invasive tumors even without a large initial tumor mass. Particular emphasis is given to early metastasis, occurring in initial cancer stages and often leading to misdiagnosis, which adversely affects survival and prognosis. The present review highlighted the need for improved understanding and detection methods for early metastasis, which has not been effectively identified clinically. The present review demonstrated the clinicopathological and molecular characteristics of early­onset metastatic types of cancer, noting factors such as age, race, tumor size and location as well as the histological and pathological grade as significant predictors. In conclusion, the present review underscored the importance of early detection and management of metastatic types of cancer and called for improved predictive models, including advanced techniques such as nomograms and machine learning, so as to enhance patient outcomes, acknowledging the challenges and limitations of the current research as well as the necessity for further studies.


Subject(s)
Neoplasms , Nomograms , Humans , Neoplasm Staging , Prognosis , Neoplasms/diagnosis , Neoplasms/genetics
15.
Heliyon ; 10(5): e27071, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38463784

ABSTRACT

Background: Lung cancer metastasis to the brain presents significant clinical challenges. Therefore, elucidating its underlying mechanisms and characterizing its transcriptomic landscape is essential for developing therapeutic interventions. Methods: We analyzed two distinct single-cell RNA sequencing datasets of lung cancer metastasis to analyze the evolutionary trajectory of brain metastatic tumors. In addition, a systematic comparison of cell-cell interaction between tumor cells and lymphocytes was conducted within primary and brain metastatic tumors. Results: The brain metastatic tumors showed greater transcriptomic changes (reflected by a higher pseudotime) than tumors in the lymph nodes and primary tumors. Furthermore, our investigation has not only revealed specific shared ligand-receptor pairs in both mLN and mBrain, exemplified by the interaction between SPP1 and CD99 in T cells, but has also unveiled a diverse array of ligand-receptor pairs exclusive to the mBrain. Notably, this includes distinctive pairs such as APP and IL1 observed specifically in myeloid cells. Conclusion: The distinct microenvironment in the brain may influence the observed transcriptomic changes in tumors, emphasizing the significance of the specific environment in determining tumor behavior and therapeutic response.

16.
J Adv Nurs ; 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38258627

ABSTRACT

AIMS: To describe the changes in moderate-to-late preterm infants' (MLPIs) growth during 12 months of corrected age (CA) and to examine the predictive role of NICU-related stress, postpartum depression trajectory and family coping ability on the physical developmental trajectory of MLPIs. DESIGN: A prospective longitudinal study. METHODS: There were 237 mother-infant dyads with at least two follow-up data records included. General characteristics and NICU-related stress were recorded from medical records at baseline. Infants' physical growth was measured at 40 weeks, 1, 3, 6, 9 and 12 months CA during outpatient follow-up. Maternal postpartum depressive symptoms and family coping ability were assessed by questionnaires at 1, 3, 6, 9 and 12 months CA and 1 month CA respectively. We investigated the modifiable factors inside and outside of NICU on the trajectories of physical growth in the first year in MLPIs, mainly by using latent growth curve models with time-varying covariates. RESULTS: The curved trajectories of weight, length and head circumference in the first year in MLPIs demonstrated gradually slowed growth rates and these infants were above the WHO growth standards for the same age and sex. The latent growth curve models indicated that more NICU-related stress was negatively associated with the weight and length at 40 weeks CA, and family coping ability (parent-child relationship) at 1 month CA was associated with the growth rate of weight. Besides, more NICU-related stress predicted faster length growth rate. The infants of mothers who were in the group of high-level postpartum depression trajectory had a slower growth rate of head circumference. CONCLUSIONS: Our study identified the modifiable factors along the care continuum influencing the trajectory of MLPIs' physical growth. Nurses should receive more training about infant stress measurement and family-centred care to work in partnership with parents so that MLPIs can reach their full developmental potential. Also, multidisciplinary interventions including stress reduction strategies, close psychological monitoring and education improving parent-infant relationships should be further developed to achieve optimizing growth in the first year of MLPIs. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: It is recommended that nurses pay attention to the long-term physical growth status of MLPIs, and closely support their families. Quantifying NICU-related stress and developing reduction strategies should be the priority for clinical staff during hospitalization. After discharge, persistent screening of depressive symptoms, psychological intervention and education about the parent-child relationship need to be included in the follow-up visits. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. The study only included patients who were research participants.

17.
BMC Ophthalmol ; 24(1): 41, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38279089

ABSTRACT

OBJECTIVE: This study aimed to investigate the potential involvement of vasoactive intestinal polypeptide (VIP) in myopia development and its contribution to the mechanism of action of the anti-myopia drug, atropine. METHODS: Thirty-three-week-old guinea pigs were randomly divided into normal control (NC, n = 10), monocularly form-deprived (FDM, n = 10), and FDM treated with 1% atropine (FDM + AT, n = 10) groups. The diopter and axial length were measured at 0, 2, and 4 weeks. Guinea pig eyeballs were removed at week four, fixed, and stained for morphological changes. Immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to evaluate VIP protein and mRNA levels. RESULTS: The FDM group showed an apparent myopic shift compared to the control group. The results of the H&E staining were as follows: the cells of the inner/outer nuclear layers and retinal ganglion cells were disorganized; the choroidal thickness (ChT), blood vessel lumen, and area were decreased; the sclera was thinner, with disordered fibers and increased interfibrillar space. IHC and ISH revealed that VIP's mRNA and protein expressions were significantly up-regulated in the retina of the FDM group. Atropine treatment attenuated FDM-induced myopic shift and fundus changes, considerably reducing VIP's mRNA and protein expressions. CONCLUSIONS: The findings of elevated VIP mRNA and protein levels observed in the FDM group indicate the potential involvement of VIP in the pathogenesis and progression of myopia. The ability of atropine to reduce this phenomenon suggests that this may be one of the molecular mechanisms for atropine to control myopia.


Subject(s)
Myopia , Vasoactive Intestinal Peptide , Animals , Guinea Pigs , Atropine/pharmacology , Myopia/genetics , Retina/metabolism , RNA, Messenger/genetics , Disease Models, Animal
18.
Int Immunopharmacol ; 128: 111494, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38218012

ABSTRACT

BACKGROUND & AIMS: Tumor-associated macrophages (TAMs) are main components of immune cells in tumor microenvironment (TME), and play a crucial role in tumor progression. Tripartite motif-containing protein 65 (TRIM65) has been associated with tumor progression. However, whether TRIM65 regulate the interaction of tumor cell and TAMs in HCC and the underlying mechanisms remain unknown. In this study, we investigated the role of TRIM65 in TME of HCC and explored its underlying mechanisms. METHODS: The relation of TRIM65 expression level with tumor grades, TNM stages, and worse prognosis of HCC patients was evaluated by bioinformatics analysis, as well as immune infiltration level of macrophages. TRIM65 shRNA was transfected into HepG2 cells, and TRIM65 overexpression plasmid was transfected into Huh7 cells, and the effect of TRIM65 on cell growth was examined by EdU assay. The mouse subcutaneous Hep1-6 tumor-bearing model with WT and TRIM65-/- mice was established to study the role of TRIM65 in HCC. Immunohistochemistry staining, Immunofluorescence staining, qRT-PCR and western blot were performed to evaluate the effect of TRIM65 on TAM infiltration, TAM polarization and JAK1/STAT1 signaling pathway. RESULTS: Bioinformatics analysis revealed that TRIM65 was upregulated in 16 types of cancer especially in HCC, and high level of TRIM65 was strongly correlated with higher tumor grades, TNM stages, and worse prognosis of patients with HCC as well as immune infiltration level of macrophages (M0, M1, and M2). Moreover, we observed that TRIM65 shRNA-mediated TRIM65 knockdown significantly inhibited the HepG2 cells growth while TRIM65 overexpression highly increased the Huh7 cells growth in vitro. TRIM65 knockout significantly inhibited the tumor growth as well as macrophages polarization towards M2 but promoted macrophages polarization towards M1 in vivo. Mechanistically, the results demonstrate that TRIM65 knockout promoted macrophage M1 polarization in conditioned medium-stimulated peritoneal macrophages and in tumor tissues by activating JAK1/STAT1 signaling pathway. CONCLUSIONS: Taken together, our study suggests that tumor cells utilize TRIM65-JAK1/STAT1 axis to inhibit macrophage M1 polarization and promote tumor growth, reveals the role of TRIM65 in TAM-targeting tumor immunotherapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Humans , Mice , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Janus Kinase 1/metabolism , Liver Neoplasms/metabolism , RNA, Small Interfering/metabolism , Signal Transduction , STAT1 Transcription Factor/metabolism , Tripartite Motif Proteins/metabolism , Tumor Microenvironment , Tumor-Associated Macrophages/metabolism , Ubiquitin-Protein Ligases/metabolism
19.
Sci China Life Sci ; 67(2): 301-319, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37864082

ABSTRACT

Mitochondrial toxicity induced by therapeutic drugs is a major contributor for cardiotoxicity, posing a serious threat to pharmaceutical industries and patients' lives. However, mitochondrial toxicity testing is not incorporated into routine cardiac safety screening procedures. To accurately model native human cardiomyocytes, we comprehensively evaluated mitochondrial responses of adult human primary cardiomyocytes (hPCMs) to a nucleoside analog, remdesivir (RDV). Comparison of their response to human pluripotent stem cell-derived cardiomyocytes revealed that the latter utilized a mitophagy-based mitochondrial recovery response that was absent in hPCMs. Accordingly, action potential duration was elongated in hPCMs, reflecting clinical incidences of RDV-induced QT prolongation. In a screen for mitochondrial protectants, we identified mitochondrial ROS as a primary mediator of RDV-induced cardiotoxicity. Our study demonstrates the utility of hPCMs in the detection of clinically relevant cardiac toxicities, and offers a framework for hPCM-based high-throughput screening of cardioprotective agents.


Subject(s)
Induced Pluripotent Stem Cells , Myocytes, Cardiac , Humans , Cardiotoxicity/etiology , Cells, Cultured , Toxicity Tests/methods
20.
Medicine (Baltimore) ; 102(50): e36511, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38115268

ABSTRACT

Exercise rehabilitation can improve the prognosis of patients with coronary heart disease. However, a bibliometric analysis of the global exercise rehabilitation for coronary heart disease (CHD) research topic is lacking. This study investigated the development trends and research hotspots in the field of coronary heart disease and exercise rehabilitation. CiteSpace software was used to analyze the literature on exercise therapy for CHD in the Web of Science Core Collection database. We analyzed the data of countries/institutions, journals, authors, keywords, and cited references. A total of 3485 peer-reviewed papers were found, and the number of publications on the topic has steadily increased. The most productive country is the USA (1125), followed by China (477) and England (399). The top 3 active academic institutions are Research Libraries UK (RLUK) (236), Harvard University (152), and the University of California System (118). The most commonly cited journals are Circulation (2596), The most commonly cited references are "Exercise-based cardiac rehabilitation for coronary heart disease" (75), Lavie CJ had published the most papers (48). World Health Organization was the most influential author (334 citations). The research frontier trends in this field are body composition, participation, and function. Research on the effects of physical activity or exercise on patients with CHD is a focus of continuous exploration in this field. This study provides a new scientific perspective for exercise rehabilitation and CHD research and gives researchers valuable information for detecting the current research status, hotspots, and emerging trends for further research.


Subject(s)
Cardiac Rehabilitation , Coronary Disease , Humans , Exercise Therapy , Exercise , Bibliometrics
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