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1.
Diabetes Metab Syndr Obes ; 17: 2607-2617, 2024.
Article in English | MEDLINE | ID: mdl-38953012

ABSTRACT

Background: Lower extremity peripheral artery disease (LEAD) is a significant chronic complication of type 2 diabetes mellitus (T2DM) that significantly contributes to disability and mortality. The subtle presentation of LEAD symptoms often leads to underrecognition and misdiagnosis. Therefore, identifying simple and effective evaluation indicators is essential for the early detection and management of LEAD. Insulin resistance is closely associated with diabetes and its complications. However, the specific relationship between insulin resistance-measured by the triglyceride-glucose (TyG) index-and obesity indicators in relation to LEAD remains unclear. Objective: This study aims to investigate the association between the TyG index and its combination with obesity indicators in participants with T2DM and LEAD. Methods: We performed a univariate analysis on 3176 T2DM patients to identify risk factors for LEAD. Patients were then divided into quartiles based on the TyG index combined with various obesity indicators. The chi-square test was used to compare the prevalence of LEAD across these groups. Logistic regression analysis was conducted to examine the association between the TyG index, in combination with different obesity indicators, and the occurrence of LEAD. Finally, we assessed the predictive ability of the TyG index combined with obesity indicators for LEAD by comparing the area under the ROC curve (AUC). Results: The study included 3176 T2DM patients (1691 males and 1485 females) with a mean age of 56.16±10.60 years. Among them, 106 individuals had LEAD. The prevalence of LEAD varied significantly across quartiles of the TyG index, TyG-WC, and TyG-WHR (Q4 > Q3 > Q2 > Q1; P < 0.05). Multiple logistic regression analysis showed that the TyG index, TyG-WC, and TyG-WHR were positively associated with the risk of LEAD in T2DM patients. ROC curve analysis identified the best cutoff values for predicting LEAD: 9.8059 for the TyG index (sensitivity: 49.1%, specificity: 67.9%, AUC: 0.583), 808.8397 for TyG-WC (sensitivity: 70.8%, specificity: 47.8%, AUC: 0.603), and 8.8543 for TyG-WHR (sensitivity: 75.5%, specificity: 44.6%, AUC: 0.607). Conclusion: In T2DM patients, the TyG index, TyG-WHR, and TyG-WC are positively associated with the occurrence of LEAD. TyG-WHR and TyG-WC exhibit a stronger correlation with LEAD compared to the TyG index alone, indicating their superior diagnostic value.

2.
Adv Sci (Weinh) ; : e2403158, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38953329

ABSTRACT

In situ cancer vaccination is an attractive strategy that stimulates protective antitumor immunity. Cytotoxic T lymphocytes (CTLs) are major mediators of the adaptive immune defenses, with critical roles in antitumor immune response and establishing immune memory, and are consequently extremely important for in situ vaccines to generate systemic and lasting antitumor efficacy. However, the dense extracellular matrix and hypoxia in solid tumors severely impede the infiltration and function of CTLs, ultimately compromising the efficacy of in situ cancer vaccines. To address this issue, a robust in situ cancer vaccine, Au@MnO2 nanoparticles (AMOPs), based on a gold nanoparticle core coated with a manganese dioxide shell is developed. The AMOPs modulated the unfavorable tumor microenvironment (TME) to restore CTLs infiltration and function and efficiently induced immunogenic cell death. The Mn2+-mediated stimulator of the interferon genes pathway can be activated to further augment the therapeutic efficacy of the AMOPs. Thus, the AMOPs vaccine successfully elicited long-lasting antitumor immunity to considerably inhibit primary, recurrent, and metastatic tumors. This study not only highlights the importance of revitalizing CTLs efficacy against solid tumors but also makes progress toward overcoming TME barriers for sustained antitumor immunity.

3.
Article in English | MEDLINE | ID: mdl-38904896

ABSTRACT

Antibiotic substitutes have become a research focus due to restrictions on antibiotic usage. Among the antibiotic substitutes on the market, probiotics have been extensively researched and used. However, the mechanism by which probiotics replace antibiotics remains unclear. In this study, we aimed to investigate this mechanism by comparing the effects of probiotics and antibiotics on broiler growth performance and intestinal microbiota composition. Results shown that both probiotics and antibiotics increased daily weight gain and reduced feed conversion rate in broilers. Analysis of ileum and cecum microorganisms via 16S rRNA gene sequencing revealed that both interventions decreased intestinal microbial diversity. Moreover, the abundance of Bacteroides increased in the mature ileum, while that of Erysipelatoclostridium decreased in the cecum in response to both probiotics and antibiotics. The main metabolites of probiotics and antibiotics in the intestine were found to be organic acids, amino acids, and sugars, which might play comparable roles in growth performance. Furthermore, disaccharides and trisaccharides may be essential components in the ileum that enable probiotics to replace antibiotics. These findings provide important insights into the mechanisms underlying the use of probiotics as antibiotic substitutes in broiler breeding.

4.
Pediatr Infect Dis J ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717173

ABSTRACT

BACKGROUND: Early identification of high-risk groups of children with sepsis is beneficial to reduce sepsis mortality. This article used artificial intelligence (AI) technology to predict the risk of death effectively and quickly in children with sepsis in the pediatric intensive care unit (PICU). STUDY DESIGN: This retrospective observational study was conducted in the PICUs of the First Affiliated Hospital of Sun Yat-sen University from December 2016 to June 2019 and Shenzhen Children's Hospital from January 2019 to July 2020. The children were divided into a death group and a survival group. Different machine language (ML) models were used to predict the risk of death in children with sepsis. RESULTS: A total of 671 children with sepsis were enrolled. The accuracy (ACC) of the artificial neural network model was better than that of support vector machine, logical regression analysis, Bayesian, K nearest neighbor method and decision tree models, with a training set ACC of 0.99 and a test set ACC of 0.96. CONCLUSIONS: The AI model can be used to predict the risk of death due to sepsis in children in the PICU, and the artificial neural network model is better than other AI models in predicting mortality risk.

5.
Biomater Adv ; 161: 213895, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38795474

ABSTRACT

Ischemic stroke, a cerebrovascular disease caused by arterial occlusion in the brain, can lead to brain impairment and even death. Stem cell therapies have shown positive advantages to treat ischemic stroke because of their extended time window, but the cell viability is poor when transplanted into the brain directly. Therefore, a new hydrogel GelMA-T was developed by introducing taurine on GelMA to transplant neural stem cells. The GelMA-T displayed the desired photocuring ability, micropore structure, and cytocompatibility. Its compressive modulus was more similar to neural tissue compared to that of GelMA. The GelMA-T could protect SH-SY5Y cells from injury induced by OGD/R. Furthermore, the NE-4C cells showed better proliferation performance in GelMA-T than that in GelMA during both 2D and 3D cultures. All results demonstrate that GelMA-T possesses a neuroprotective effect for ischemia/reperfusion injury against ischemic stroke and plays a positive role in promoting NSC proliferation. The novel hydrogel is anticipated to function as cell vehicles for the transplantation of neural stem cells into the stroke cavity, aiming to treat ischemic stroke.


Subject(s)
Cell Proliferation , Hydrogels , Neural Stem Cells , Neuroprotective Agents , Taurine , Neural Stem Cells/drug effects , Neural Stem Cells/transplantation , Taurine/pharmacology , Cell Proliferation/drug effects , Neuroprotective Agents/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Animals , Cell Survival/drug effects
6.
J Ovarian Res ; 17(1): 29, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38302986

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a frequent and complicated endocrine disease that remains a major reason for infertility. Bushenhuoluo Decotion (BSHLD) has been validated to exhibit curative effects on PCOS. This study was aimed to explore the potential mechanism underlying the therapeutic action of BSHLD. METHODS: PCOS rat model was induced by dehydroepiandrosterone (DHEA). Serum hormone and cytokines levels and ovarian pathological alterations were measured to assess ovarian function. Exosomes (Exos) were identified by Transmission electron microscopy and Nanoparticle Tracking Analysis. RT-qPCR, Western blotting, immunohistochemical staining, and immunofluorescence staining were performed to detect molecule expressions. Proliferation and pyroptosis of granulosa cells (GCs) were evaluated by CCK-8 and flow cytometry, respectively. The binding relationship between miR-30a-5p and suppressor of cytokine signaling 3 (SOCS3) was verified by dual luciferase reporter and RIP assays. RESULTS: BSHLD treatment improved serum hormone abnormality, insulin sensitivity, and ovarian morphologic changes of PCOS rats. Moreover, BSHLD treatment restrained the excessive autophagy and pyroptosis in ovarian tissues of PCOS rats. Moreover, BSHLD reduced the expression of miR-30a-5p in serum, serum-derived Exos, and ovarian tissues, thus inhibiting autophagy and NLRP3-mediated pyroptosis in GCs. Mechanistically, SOCS3 was proved as a target of miR-30a-5p and could activate mTOR/P70S6K pathway to repress autophagy. The inhibitory effect of miR-30a-5p deficiency on autophagy and pyroptosis of GCs was attenuated by rapamycin. CONCLUSION: Collectively, BSHLD suppressed autophagy and pyroptosis to improve POCS by regulating exosomal miR-30a-5p/SOCS3/mTOR signaling.


Subject(s)
Drugs, Chinese Herbal , MicroRNAs , Plant Extracts , Polycystic Ovary Syndrome , Animals , Female , Humans , Rats , Autophagy , Hormones , MicroRNAs/genetics , MicroRNAs/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Polycystic Ovary Syndrome/pathology , Pyroptosis , Suppressor of Cytokine Signaling 3 Protein/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism , TOR Serine-Threonine Kinases/metabolism , Plant Extracts/therapeutic use , Drugs, Chinese Herbal/therapeutic use
7.
iScience ; 27(2): 108779, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38292420

ABSTRACT

Immune escape is identified as one of the reasons for the poor prognosis of colorectal cancer (CRC) patients. Circular RNAs are considered to promote tumor progression by mediating tumor immune escape. We discovered that higher expression of circYAP1 was associated with a worse prognosis of CRC patients. Functional experiments in vitro and in vivo showed that circYAP1 upregulation inhibited the cytotoxicity of CD8+ T cells by upregulating programmed death ligand-1 (PD-L1). Mechanistically, we found that circYAP1 directly binds to the YAP1 protein to prevent its phosphorylation, enhancing proportion of YAP1 protein in the nucleus, and that YAP1 interacts with TCF4 to target the PD-L1 promoter and initiate PD-L1 transcription in CRC cells. Taken together, circYAP1 promotes CRC immune escape and tumor progression by activating the YAP1/TCF4-PD-L1 axis and may provide a new strategy for combination immunotherapy of CRC patients.

8.
Cell Signal ; 114: 110967, 2024 02.
Article in English | MEDLINE | ID: mdl-37949382

ABSTRACT

BACKGROUND: Multiple PDZ Domain Crumbs Cell Polarity Complex Component (MPDZ) is involved in a few human cancers. However, the features and potential mechanisms of MPDZ in progression of colorectal cancer (CRC) remains unknown. METHODS: The prognostic role of MPDZ in CRC was determined by Kaplan-Meier and univariate regression analysis. Enrichment analysis was performed to characterize crucial pathways of MPDZ. Immune infiltration and immunotherapeutic outcome were further evaluated. CCK8, EDU, transwell, and wound healing assay were used to assess the influence of MPDZ on pernicious performance of CRC cells. CD8+ T cells and CRC cells were co-cultured to explore the effect of MPDZ on the tumor microenvironment. qRT-PCR, western blot, immunoprecipitation (IP), and methylated RNA immunoprecipitation (me-RIP) were implemented in seeking for the potential mechanisms of MPDZ in CRC. RESULTS: CRC patients with elevated MPDZ expression suffered from significantly worse prognosis. Enrichment analysis revealed that MPDZ involved in pathways related to metastasis and cell cycle in CRC. In addition, MPDZ expression were related to several immunoinhibitors and had the ability to predict immunotherapy response. Finally, in vitro assays demonstrated that MPDZ knockdown inhibited migration, invasion and immune evasion of CRC cells. Mechanistically, MPDZ knockdown enhanced YAP1 phosphorylation by increased LATS1 expression. Moreover, m6A-MPDZ mRNA may be recognized and degraded by m6A recognition protein YTHDF2. CONCLUSIONS: MPDZ was critical for CRC development and could be a promising candidate for the treatment of CRC patients.


Subject(s)
CD8-Positive T-Lymphocytes , Colorectal Neoplasms , Humans , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Colorectal Neoplasms/pathology , Membrane Proteins/metabolism , Phosphorylation , Transcription Factors/metabolism , Tumor Microenvironment , YAP-Signaling Proteins/metabolism
9.
Ann Med ; 55(2): 2281659, 2023.
Article in English | MEDLINE | ID: mdl-38039548

ABSTRACT

PURPOSE: Individual genetic background can play an essential role in determining the development of esophageal squamous cell carcinoma (ESCC). PTPN13 and CHEK2 play important roles in the pathogenesis of ESCC. This case-control study aimed to analyze the association between gene polymorphisms and ESCC susceptibility. METHODS: DNA was extracted from the peripheral blood of patients. The Agena MassARRAY platform was used for the genotyping. Statistical analysis was conducted using the chi-squared test or Fisher's exact test, logistic regression analysis, and stratification analysis. RESULTS: The 'G' allele of rs989902 (PTPN13) and the 'T' allele of rs738722 (CHEK2) were both associated with an increased risk of ESCC (rs989902: OR = 1.23, 95% CI = 1.02-1.47, p = 0.028; rs738722: OR = 1.28, 95% CI = 1.06-1.55, p = 0.011). Stratification analysis showed that SNPs (rs989902 and rs738722) were notably correlated with an increased risk of ESCC after stratification for age, sex, smoking, and drinking status. In addition, rs738722 might be associated with lower stage, while rs989902 had a lower risk of metastasis. CONCLUSION: Our findings display that PTPN13 rs989902 and CHEK2 rs738722 are associated with an increased risk of ESCC in the Chinese Han population.


Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Carcinoma, Squamous Cell/genetics , Genetic Predisposition to Disease , Case-Control Studies , Polymorphism, Single Nucleotide , China/epidemiology , Genotype , Checkpoint Kinase 2/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 13/genetics
10.
Cerebrovasc Dis ; 2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38154454

ABSTRACT

OBJECTIVE: This study aimed to investigate whether Functional Electrical Stimulation (FES) and Transcranial Direct Current Stimulation (tDCS) enhanced the effect of Occupational Therapy (OT) on post-stroke limb functional recovery and quality of life, using direct and network meta-analysis. METHODS: A computerized search was conducted in databases such as Medline, Web of Science, Embase, CNKI (China National Knowledge Infrastructure), Wanfang Data, and VIP Information for prospective randomized controlled trials on OT, FES, and tDCS for improving post-stroke limb motor function and quality of life, with the search cutoff date of July 1, 2023. RESULTS: Following the screening process, a total of 8 research articles were incorporated, encompassing 358 participants. Among these, 177 individuals underwent OT exclusively, while 181 individuals underwent a combined regimen of OT alongside electromagnetic therapy. In terms of the intervention methods, the control group received OT treatment only, while the experimental group employed tDCS in 5 studies and FES in 3 studies. Within these investigations, Fugl-Meyer Assessment (FMA) scores were reported in 8 studies. The aggregated mean difference (MD) for FMA scores was 5.08 (95% CI: 2.46, 7.71), with a specific MD of 2.77 (95% CI: 1.46, 4.09) for the tDCS subgroup and 9.04 (95% CI: 5.34, 12.73) for the FES subgroup. Notably, FES combined with OT exhibited significant advantages in enhancing FMA scores when compared to the combination of tDCS and OT. Furthermore, four studies provided data on modified Barthel Index (MBI) scores, yielding a collective MD of 7.20 (95% CI: 4.44, 9.95). CONCLUSION: In patients with stroke, both FES combined with OT and tDCS combined with OT exhibit substantial enhancements in limb function and quality of life compared to OT alone. Notably, FES combined with OT yields superior clinical benefits when compared to the amalgamation of tDCS and OT.

11.
Commun Biol ; 6(1): 1268, 2023 12 14.
Article in English | MEDLINE | ID: mdl-38097699

ABSTRACT

Recent developments in single-cell technology have enabled the exploration of cellular heterogeneity at an unprecedented level, providing invaluable insights into various fields, including medicine and disease research. Cell type annotation is an essential step in its omics research. The mainstream approach is to utilize well-annotated single-cell data to supervised learning for cell type annotation of new singlecell data. However, existing methods lack good generalization and robustness in cell annotation tasks, partially due to difficulties in dealing with technical differences between datasets, as well as not considering the heterogeneous associations of genes in regulatory mechanism levels. Here, we propose the scPML model, which utilizes various gene signaling pathway data to partition the genetic features of cells, thus characterizing different interaction maps between cells. Extensive experiments demonstrate that scPML performs better in cell type annotation and detection of unknown cell types from different species, platforms, and tissues.


Subject(s)
Medicine , Single-Cell Gene Expression Analysis , Signal Transduction , Technology
12.
BMC Cancer ; 23(1): 1169, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38031100

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors, influenced by several genetic loci in its clinical phenotypes. The aim of this study was to determine the relationship between the MMP8 gene polymorphism and CRC risk in the Chinese Han population. METHOD: This study recruited 688 CRC patients and 690 healthy controls. The relationship between MMP8 polymorphism and CRC susceptibility was assessed by calculating the odds ratio (OR) and 95% confidence interval (CI) after stratifying by age, gender, body mass index (BMI), smoking, and alcohol consumption under a multi-genetic model. RESULTS: MMP8 rs3740938 was associated with increased CRC predisposition (p = 0.016, OR = 1.24, 95% CI: 1.04-1.48), and this association was detected particularly in subjects aged > 60 years, females, people with BMI > 24 kg/m2, smokers, and drinkers. Moreover, rs3740938 was found to be associated with the pathological type of rectal cancer. CONCLUSIONS: Our results first displayed that rs3740938 in MMP8 was a risk factor for CRC predisposition. This finding may provide a new biological perspective for understanding the role of the MMP8 gene in CRC pathogenesis.


Subject(s)
Colorectal Neoplasms , Genetic Predisposition to Disease , Female , Humans , Genotype , Matrix Metalloproteinase 8/genetics , Polymorphism, Single Nucleotide , Risk Factors , Colorectal Neoplasms/genetics , Case-Control Studies
13.
J Med Internet Res ; 25: e44895, 2023 10 12.
Article in English | MEDLINE | ID: mdl-37824198

ABSTRACT

BACKGROUND: Machine learning is a potentially effective method for identifying and predicting the time of the onset of stroke. However, the value of applying machine learning in this field remains controversial and debatable. OBJECTIVE: We aimed to assess the value of applying machine learning in predicting the time of stroke onset. METHODS: PubMed, Web of Science, Embase, and Cochrane were comprehensively searched. The C index and sensitivity with 95% CI were used as effect sizes. The risk of bias was evaluated using PROBAST (Prediction Model Risk of Bias Assessment Tool), and meta-analysis was conducted using R (version 4.2.0; R Core Team). RESULTS: Thirteen eligible studies were included in the meta-analysis involving 55 machine learning models with 41 models in the training set and 14 in the validation set. The overall C index was 0.800 (95% CI 0.773-0.826) in the training set and 0.781 (95% CI 0.709-0.852) in the validation set. The sensitivity and specificity were 0.76 (95% CI 0.73-0.80) and 0.79 (95% CI 0.74-0.82) in the training set and 0.81 (95% CI 0.68-0.90) and 0.83 (95% CI 0.73-0.89) in the validation set, respectively. Subgroup analysis revealed that the accuracy of machine learning in predicting the time of stroke onset within 4.5 hours was optimal (training: 0.80, 95% CI 0.77-0.83; validation: 0.79, 95% CI 0.71-0.86). CONCLUSIONS: Machine learning has ideal performance in identifying the time of stroke onset. More reasonable image segmentation and texture extraction methods in radiomics should be used to promote the value of applying machine learning in diverse ethnic backgrounds. TRIAL REGISTRATION: PROSPERO CRD42022358898; https://www.crd.york.ac.uk/Prospero/display_record.php?RecordID=358898.


Subject(s)
Ethnicity , Stroke , Humans , Machine Learning , Patients , PubMed , Stroke/diagnosis
14.
J Cardiovasc Pharmacol ; 82(5): 389-399, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37851150

ABSTRACT

ABSTRACT: This study aimed to determine whether endoplasmic reticulum (ER) stress is involved in impaired autophagy after myocardial ischemia/reperfusion (M-I/R) and elucidate the underlying mechanisms. The expression levels of stimulator of interferon gene (STING) and interferon regulatory transcription factor 3 (IRF3) phosphorylation increased in M-I/R heart tissues and hypoxia-treated/reoxygenation-treated H9c2 cells. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) significantly suppressed the stimulation of STING-IRF3 transcription and alleviated cardiac dysfunction caused by M-I/R injury. In addition, 4-PBA reversed ischemia-induced/reperfusion-induced autophagic flux dysfunction, as demonstrated by a decrease in p 62 and LC3 levels. Similarly, the protective effect of STING deficiency on myocardial cell damage was achieved by the recovery of autophagic flux. Conversely, the protective effect of 4-PBA against hypoxia/reoxygenation injury in cardiomyocytes was offset by STING overexpression, wherein the activated STING-IRF3 pathway promoted the expression of Rubicon (a negatively-regulated autophagic molecule) by binding to the Rubicon promoter. Rubicon ablation effectively counteracts the adverse effects of STING overexpression in cardiomyocytes. The data showed that STING-IRF3 signaling of ER stress receptors is particularly important in the progression of physiological M-I/R caused by the inhibition of autophagic flow in vivo and in vitro.


Subject(s)
Apoptosis , Myocardial Ischemia , Humans , Signal Transduction , Myocytes, Cardiac , Myocardial Ischemia/metabolism , Autophagy , Hypoxia/metabolism , Ischemia/metabolism , Endoplasmic Reticulum Stress , Reperfusion , Interferons/metabolism , Interferons/pharmacology , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon Regulatory Factor-3/pharmacology
15.
Research (Wash D C) ; 6: 0189, 2023.
Article in English | MEDLINE | ID: mdl-37727321

ABSTRACT

Offensive language detection has received important attention and plays a crucial role in promoting healthy communication on social platforms, as well as promoting the safe deployment of large language models. Training data is the basis for developing detectors; however, the available offense-related dataset in Chinese is severely limited in terms of data scale and coverage when compared to English resources. This significantly affects the accuracy of Chinese offensive language detectors in practical applications, especially when dealing with hard cases or out-of-domain samples. To alleviate the limitations posed by available datasets, we introduce AugCOLD (Augmented Chinese Offensive Language Dataset), a large-scale unsupervised dataset containing 1 million samples gathered by data crawling and model generation. Furthermore, we employ a multiteacher distillation framework to enhance detection performance with unsupervised data. That is, we build multiple teachers with publicly accessible datasets and use them to assign soft labels to AugCOLD. The soft labels serve as a bridge for knowledge to be distilled from both AugCOLD and multiteacher to the student network, i.e., the final offensive detector. We conduct experiments on multiple public test sets and our well-designed hard tests, demonstrating that our proposal can effectively improve the generalization and robustness of the offensive language detector.

16.
Biochem Biophys Res Commun ; 680: 127-134, 2023 11 05.
Article in English | MEDLINE | ID: mdl-37738902

ABSTRACT

Homeodomain (HD)-containing proteins are typically recognized as transcription factors. Engrailed 2 (EN2) is an HD-containing protein that is highly expressed in various types of cancers, however, the mechanism underlying the biological function of EN2 is not fully understood. Here, we report a transcription-independent function of EN2 in addition to its role as a transcription factor. EN2 expression leads to the activation of multiple signaling pathways mediated by phosphorylation cascades. A phosphoproteomic analysis revealed that the phosphorylation status of numerous protein sites was altered after EN2 is expressed. Notably, EN2 was shown to interact with a myriad of proteins implicated in phosphorylation signaling cascades, as determined by immunoprecipitation-mass spectrometry (IP-MS). We validated the interaction between EN2 and B55α, the regulatory subunit of the PP2A-B55α complex, and confirmed that the phosphatase activity of the complex was suppressed by EN2 binding. To target EN2-induced malignancy, two kinds of small molecules were utilized to inhibit the EN2-activated NF-κB and AKT signaling pathways. A clear synergistic effect was observed when the activation of the two pathways was simultaneously blocked. Collectively, the data show that EN2 functions in a transcription-independent manner in addition to its role as a transcription factor. This finding may have therapeutic implications in treating esophageal squamous cell carcinoma (ESCC).


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Phosphorylation , Nerve Tissue Proteins/metabolism , Signal Transduction , Homeodomain Proteins/metabolism , Transcription Factors/metabolism
17.
Arch Microbiol ; 205(10): 337, 2023 Sep 23.
Article in English | MEDLINE | ID: mdl-37740776

ABSTRACT

EmbR, a substrate of pknH in Mycobacterium tuberculosis (Mtb), is related to the ethambutol (EMB) resistance. This study aimed to investigate the relationship between acetylation of pknH and the resistance of EMB mono-resistant Mtb. The EMB mono-resistant Mtb strain was constructed based on the MYCOTB and the Löwenstein-Jensen (LJ) proportion method. The growth kinetics was used to evaluate the bacterial growth. Escherichia coli, as the host of Mtb, was used for cloning and protein purification. Moreover, the immunoprecipitation was performed along with western blot to evaluate the EmbR phosphorylation and pknH acetylation. Each independent experiment was conducted in triplicate. EMB mono-resistant Mtb strain was successfully constructed according to the results of MIC values of 14 anti-Mtb drugs. The EMB resistant (ER) Mtb strain showed faster growth than the wild-type (WT) Mtb strain, and the difference was statistically significant. Moreover, pknH robustly phosphorylates EmbR, and pknH and acetylated pknH protein levels were downregulated in ER strain. The acetylation of pknH may reduce the phosphorylation of EmbR to inhibit the growth of Mtb strain. Enhancing the acetylation of pknH may be a promising method to inhibit the EMB resistance against Mtb.

18.
Gen Hosp Psychiatry ; 84: 47-59, 2023.
Article in English | MEDLINE | ID: mdl-37385139

ABSTRACT

PURPOSE: This meta-analysis was to assess the efficacy of digital psychological interventions to improve physical symptoms (i.e., fatigue, pain, disturbed sleep, and physical well-being) among cancer patients, as well as to evaluate the variables that possibly moderate intervention effects. METHODS: Nine databases were searched for the literature up to February 2023. Two reviewers independently conducted a quality assessment. Effect sizes were reported as the standardized mean difference (Hedge's g) and estimated using a random-effects model. RESULTS: The meta-analysis included 44 randomized clinical trials comprising 7200 adults with cancer. Digital psychological interventions were associated with significant improvements in short-term fatigue (g = -0.33; 95% CI, -0.58 to -0.07) and disturbed sleep (g = -0.36; 95% CI, -0.57 to -0.15), but with non-significant changes in pain (g = -0.23; 95% CI, -0.68 to 0.21) and physical well-being (g = 0.31; 95% CI, -0.18 to 0.80). Additionally, no alleviation in long-term physical symptoms was observed. In subgroup analysis, results suggest that the country significantly moderated the effectiveness of digital psychological interventions in alleviating fatigue. CONCLUSIONS: Digital psychological interventions can be effective for improving short-term fatigue and disturbed sleep in patients with cancer. Clinicians could consider digital psychological interventions as a possible and efficient addition to better manage some of the physical symptoms during and after cancer treatment.


Subject(s)
Neoplasms , Psychosocial Intervention , Adult , Humans , Anxiety/therapy , Neoplasms/complications , Pain , Fatigue/etiology , Fatigue/therapy
19.
Zhen Ci Yan Jiu ; 48(5): 494-9, 2023 May 25.
Article in Chinese | MEDLINE | ID: mdl-37247864

ABSTRACT

OBJECTIVE: To observe the clinical effect and advantages of dynamic and static acupuncture method combined with manual reduction on posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV). METHODS: Ninety patients with PC-BPPV who met the inclusion criteria were randomly divided into manual reduction control group, acupuncture control group and experimental group, with 30 cases in each group. Epley reduction method was used for manual reduction control treatment of patients in the manual reduction control group, until there was no obvious vertigo of patients. Patients in the acupuncture control group received ordinary acupuncture treatment, while patients in the experiment group received dynamic and static acupuncture treatment, both on the basis of manual reduction control treatment. Baihui(GV20) and Yintang(GV24+), Sanyinjiao(SP6), Zhongzhu(TE3), Houxi(SI3) and Waiguan(TE5) on the healthy side, and the vertigo-auditory area and Fengchi(GB20) on the affected side were selected for acupuncture intervention, which was performed once a day, with needles retained for 30 minutes in two acupuncture groups. Every six times was taken as a session and two sessions were required. Dizziness handicap inventory (DHI) scale and visual analogue score (VAS) were used to evaluate the degree of vertigo before, after 1 and 2 sessions of treatment respectively. RESULTS: Compared with those before treatment, the DHI score and VAS score of each group after 1 and 2 sessions of treatment were both significantly decreased (P<0.05). Compared with the acupuncture control group and the manual reduction control group, the DHI score of the experiment group was significantly decreased (P<0.05) after 1 and 2 sessions of treatment. VAS score of the experiment group was significantly decreased compared with that of the manual reduction control group(P<0.05) after 1 and 2 sessions of treatment. The total effective rate of the experiment group was 86.67%, better than those of the acupuncture control group (83.33%, P<0.05) and the manual reduction control group(66.67%, P<0.05). CONCLUSION: The dynamic and static acupuncture method combined with manual reduction effectively improved vertigo symptoms in PC-BPPV with rapid and lasting effects, which is worthy of further clinical promotion and application.


Subject(s)
Acupuncture Therapy , Benign Paroxysmal Positional Vertigo , Humans , Benign Paroxysmal Positional Vertigo/diagnosis , Benign Paroxysmal Positional Vertigo/therapy , Dizziness , Semicircular Canals
20.
Zhongguo Zhen Jiu ; 43(5): 545-51, 2023 May 12.
Article in Chinese | MEDLINE | ID: mdl-37161808

ABSTRACT

OBJECTIVE: To observe the effects of electroacupuncture at "Siguan" points on behavior, colonic 5-hydroxytryptamine (5-HT) and fecal short-chain fatty acids (SCFAs) in rats with post-stroke depression (PSD), and explore the effect mechanism of electroacupuncture at Siguan points on PSD. METHODS: Fifty SD rats were randomly divided into a sham-operation group, a stroke group, a PSD group, a drug group and an electroacupuncture group, with 10 rats in each one. The stroke model was established by middle cerebral artery occlusion (MCAO) method in the stroke group; except for the sham-operation group, the rats in the other groups were intervened with MCAO combined with solitary and chronic unpredictable mild stress (CUMS) to establish PSD model. In the electroacupuncture group, electroacupuncture was delivered at "Hegu" (LI 4) and "Taichong" (LR 3), with disperse-dense wave, 2 Hz/10 Hz in frequency, for 30 min in each intervention, once daily, for consecutive 21 days. Simultaneously, distilled water (0.01 L•kg-1•d-1) was administrated intragastrically. Fluoxetine solution (2.33 mg•kg-1•d-1) was given by gavage , once a day and for 21 days in the drug group. The same procedure of fixation and gavage with distilled water were adopted in the sham-operation group, the stroke group and the PSD group. Separately, before stroke modeling, after PSD modeling and after 21-day intervention, the consumption of sugar water and the scores of horizontal movement and vertical movement in open-field test were observed. After 21-day intervention, the content of colonic 5-HT was detected by immunohistochemical method, and that of fecal SCFAs was determined by gas chromatography mass spectrometry. RESULTS: After PSD modeling, compared with the stroke group, the sugar water consumption, the horizontal movement scores and vertical movement scores of the open-field test were all reduced in the PSD group, the drug group and the electroacupuncture group (P<0.05). After 21-day intervention, the sugar water consumption and the scores of horizontal movement and vertical movement of the open-field test were increased in the drug group and the electroacupuncture group (P<0.05) when compared with the PSD group; and the horizontal movement score in the electroacupuncture group was lower than that of the drug group (P<0.05). Compared with the sham-operation group, the contents of total fecal SCFAs and acetic acid were lower in the stroke group (P<0.05), and the contents of colonic 5-HT and total fecal SCFAs, acetic acid, propionic acid and butyric acid were reduced in the PSD group (P<0.05). In comparison with the PSD group, the contents of colonic 5-HT and total fecal SCFAs, acetic acid and propionic acid were increased in the drug group and the electroacupuncture group (P<0.05); and the content of colonic 5-HT in the electroacupuncture group was lower than that of the drug group (P<0.05). The level of colonic 5-HT was positively correlated with the contents of total fecal SCFAs and propionic acid (r=0.424, P=0.005; r=0.427, P=0.004). CONCLUSION: Electroacupuncture at "Siguan" points can relieve the depression-like behavior of PSD rats, and its underlying mechanism may be related to the regulation of fecal SCFAs, which affects the release of colonic 5-HT.


Subject(s)
Electroacupuncture , Stroke , Animals , Rats , Rats, Sprague-Dawley , Propionates , Serotonin , Depression/etiology , Depression/therapy , Fatty Acids, Volatile , Stroke/complications , Acetic Acid , Butyric Acid , Water
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