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1.
Adv Sci (Weinh) ; : e2400451, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828672

ABSTRACT

Wound infections pose a major healthcare issue, affecting the well-being of millions of patients worldwide. Effective intervention and on-site detection are important in wound management. However, current approaches are hindered by time-consuming analysis and a lack of technology for real-time monitoring and prompt therapy delivery. In this study, a smart wound patch system (SWPS) designed for wireless closed-loop and in-situ wound management is presented. The SWPS integrates a microfluidic structure, an organic electrochemical transistor (OECT) based sensor, an electrical stimulation module, and a miniaturized flexible printed circuit board (FPCB). The OECT incorporates a bacteria-responsive DNA hydrogel-coated gate for continuous monitoring of bacterial virulence at wound sites. Real-time detection of OECT readings and on-demand delivery of electrical cues to accelerate wound healing is facilitated by a mobile phone application linked with an FPCB containing low-power electronics equipped with parallel sensing and stimulation circuitry. In this proof-of-concept study, the functionality of the SWPS is validated and its application both in vitro and in vivo is demonstrated. This proposed system expands the arsenal of tools available for effective wound management and enables personalized treatment.

2.
Anal Methods ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829181

ABSTRACT

The level of sulfur dioxide (SO2) and viscosity in mitochondria play vital roles in various physiological and pathological processes. Abnormalities in mitochondrial SO2 and viscosity are closely associated with numerous biological diseases. It is of great significance to develop novel fluorescence probes for simultaneous detection of SO2 and viscosity within mitochondria. Herein, we have developed a water-soluble, mitochondrial-targeted and near-infrared fluorescent probe, CMBT, for the simultaneous detection of SO2 and viscosity. The probe CMBT incorporates benzothiazolium salt as a mitochondrial targeting moiety and 7-diethylaminocoumarin as a rotor for viscosity detection, respectively. Based on the prompt reaction between nucleophilic HSO3-/SO32- and the backbone of the benzothiazolium salt derivative, probe CMBT displayed high sensitivity and selectivity toward SO2 with a limit of detection as low as 0.17 µM. As viscosity increased, the twisted intramolecular charge transfer (TICT) process was restricted, resulting in fluorescence emission enhancement at 690 nm. Moreover, probe CMBT demonstrated exceptional mitochondrial targeting ability and was successfully employed to image variations of SO2 and viscosity in living cells and mice. The work highlights the great potential of the probe as a convenient tool for revealing the relationship between SO2 and viscosity in biological systems.

3.
Mol Neurobiol ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829513

ABSTRACT

Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1ß, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4+) and calcitonin gene-related peptide-positive (CGRP+) neurons, rather than neurofilament 200-positive (NF200+) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1ß and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain.

4.
Ren Fail ; 46(1): 2338484, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38832469

ABSTRACT

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.


Subject(s)
Acute Kidney Injury , Bibliometrics , COVID-19 , Pandemics , SARS-CoV-2 , Humans , COVID-19/complications , COVID-19/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Coronavirus Infections/epidemiology , Coronavirus Infections/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/complications , Italy/epidemiology , Betacoronavirus , China/epidemiology , Global Health
6.
Front Cell Infect Microbiol ; 14: 1363276, 2024.
Article in English | MEDLINE | ID: mdl-38707511

ABSTRACT

Introduction: Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD. Methods: To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses. Results: The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism. Discussion: Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.


Subject(s)
Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Renal Insufficiency, Chronic , Gastrointestinal Microbiome/genetics , Humans , RNA, Ribosomal, 16S/genetics , Renal Insufficiency, Chronic/microbiology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Feces/microbiology , Phylogeny , Faecalibacterium prausnitzii/genetics , Biodiversity , Dysbiosis/microbiology
7.
Heliyon ; 10(10): e31293, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813155

ABSTRACT

Background: Several studies have shown that bedside lung ultrasound findings in postanaesthesia care units (PACUs) and intensive care units (ICUs) correlate with postoperative pulmonary complications(PPCs) after noncardiac major surgery. However, it remains unclear whether lung ultrasound findings can be used as early predictors of PPCs in patients undergoing cardiac surgery. The main aim of our study was to evaluate the relationship between early postoperative point-of-care lung ultrasound findings and PPCs after cardiac surgery. Methods: Two board-certified physicians performed a point-of-care pulmonary ultrasound on cardiac surgery patients approximately 2 h after the patient was admitted to the ICU. Pulmonary complications occurring within 30 days postoperatively were recorded. Logistic regression modeling was used to analyze the relationship between lung ultrasound findings and PPCs. Results: PPCs occurred in 61 (30.9 %) of the 197 patients. Lung ultrasound scores(LUS), number of lung consolidation(NLC), and depth of pleural effusion(DPE) were more significant in patients who developed PPCs (P < 0.001). According to the multivariate analysis, NLC≥3(aOR 2.71,95%CI 1.14-6.44; p = 0.024)and DPE >0.95(aOR 3.79,95%CI 1.60-8.99; p = 0.002) were found to be independently associated with PPCs during this study. Conclusions: Our study demonstrated that DPE >0.95 and NLC ≥3 were associated with PPCs after cardiac surgery based on bedside lung ultrasound findings in the ICU. When these signs manifest perioperatively, the surgeon should be alerted and the necessary steps should be taken, especially if they present simultaneously.

8.
Article in English | MEDLINE | ID: mdl-38758667

ABSTRACT

OBJECTIVE: Synthesizing and evaluating inconsistent medical evidence is essential in evidence-based medicine. This study aimed to employ ChatGPT as a sophisticated scientific reasoning engine to identify conflicting clinical evidence and summarize unresolved questions to inform further research. MATERIALS AND METHODS: We evaluated ChatGPT's effectiveness in identifying conflicting evidence and investigated its principles of logical reasoning. An automated framework was developed to generate a PubMed dataset focused on controversial clinical topics. ChatGPT analyzed this dataset to identify consensus and controversy, and to formulate unsolved research questions. Expert evaluations were conducted 1) on the consensus and controversy for factual consistency, comprehensiveness, and potential harm and, 2) on the research questions for relevance, innovation, clarity, and specificity. RESULTS: The gpt-4-1106-preview model achieved a 90% recall rate in detecting inconsistent claim pairs within a ternary assertions setup. Notably, without explicit reasoning prompts, ChatGPT provided sound reasoning for the assertions between claims and hypotheses, based on an analysis grounded in relevance, specificity, and certainty. ChatGPT's conclusions of consensus and controversies in clinical literature were comprehensive and factually consistent. The research questions proposed by ChatGPT received high expert ratings. DISCUSSION: Our experiment implies that, in evaluating the relationship between evidence and claims, ChatGPT considered more detailed information beyond a straightforward assessment of sentimental orientation. This ability to process intricate information and conduct scientific reasoning regarding sentiment is noteworthy, particularly as this pattern emerged without explicit guidance or directives in prompts, highlighting ChatGPT's inherent logical reasoning capabilities. CONCLUSION: This study demonstrated ChatGPT's capacity to evaluate and interpret scientific claims. Such proficiency can be generalized to broader clinical research literature. ChatGPT effectively aids in facilitating clinical studies by proposing unresolved challenges based on analysis of existing studies. However, caution is advised as ChatGPT's outputs are inferences drawn from the input literature and could be harmful to clinical practice.

9.
Cancer Immunol Immunother ; 73(7): 131, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748299

ABSTRACT

PURPOSE: The variable responses to immunotherapy observed in gastric cancer (GC) patients can be attributed to the intricate nature of the tumor microenvironment. Glutathione (GSH) metabolism significantly influences the initiation and progression of gastric cancer. Consequently, targeting GSH metabolism holds promise for improving the effectiveness of Immune checkpoints inhibitors (ICIs). METHODS: We investigated 16 genes related to GSH metabolism, sourced from the MSigDB database, using pan-cancer datasets from TCGA. The most representative prognosis-related gene was identified for further analysis. ScRNA-sequencing analysis was used to explore the tumor heterogeneity of GC, and the results were confirmed by  Multiplex immunohistochemistry (mIHC). RESULTS: Through DEGs, LASSO, univariate and multivariate Cox regression analyses, and survival analysis, we identified GGT5 as the hub gene in GSH metabolism with the potential to promote GC. Combining CIBERSORT, ssGSEA, and scRNA analysis, we constructed the immune architecture of GC. The subpopulations of T cells were isolated, revealing a strong association between GGT5 and memory CD8+ T cells. Furthermore, specimens from 10 GC patients receiving immunotherapy were collected. mIHC was used to assess the expression levels of GGT5 and memory CD8+ T cell markers. Our results established a positive correlation between GGT5 expression, the enrichment of memory CD8+ T cells, and a suboptimal response to immunotherapy. CONCLUSIONS: Our study identifies GGT5, a hub gene in GSH metabolism, as a potential therapeutic target for inhibiting the response to immunotherapy in GC patients. These findings offer new insights into strategies for optimizing immunotherapy of GC.


Subject(s)
CD8-Positive T-Lymphocytes , Glutathione , Immunotherapy , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/immunology , Stomach Neoplasms/metabolism , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Glutathione/metabolism , Immunotherapy/methods , Tumor Microenvironment/immunology , Prognosis , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Female , Biomarkers, Tumor/metabolism , Male , gamma-Glutamyltransferase/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology
10.
Mol Cancer ; 23(1): 102, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755678

ABSTRACT

Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.


Subject(s)
Drug Resistance, Neoplasm , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , RNA, Circular , TOR Serine-Threonine Kinases , Triple Negative Breast Neoplasms , Humans , RNA, Circular/genetics , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Drug Resistance, Neoplasm/genetics , Animals , Female , Mice , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Neoplasm Metastasis , Tripartite Motif Proteins/metabolism , Tripartite Motif Proteins/genetics , Signal Transduction , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Prognosis
11.
J Hazard Mater ; 473: 134587, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38772107

ABSTRACT

One of the factors influencing the behavior of arsenic (As) in environment is microbial-mediated As transformation. However, the detailed regulatory role of gene expression on the changes of root exudation, rhizosphere microorganisms, and soil As occurrence forms remains unclear. In this study, we evidence that loss-of-function of OsSAUR2 gene, a member of the SMALL AUXIN-UP RNA family in rice, results in significantly higher As uptake in roots but greatly lower As accumulation in grains via affecting the expression of OsLsi1, OsLsi2 in roots and OsABCC1 in stems. Further, the alteration of OsSAUR2 expression extensively affects the metabolomic of root exudation, and thereby leading to the variations in the composition of rhizosphere microbial communities in rice. The microbial community in the rhizosphere of Ossaur2 plants strongly immobilizes the occurrence forms of As in soil. Interestingly, Homovanillic acid (HA) and 3-Coumaric acid (CA), two differential metabolites screened from root exudation, can facilitate soil iron reduction, enhance As bioavailability, and stimulate As uptake and accumulation in rice. These findings add our further understanding in the relationship of OsSAUR2 expression with the release of root exudation and rhizosphere microbial assembly under As stress in rice, and provide potential rice genetic resources and root exudation in phytoremediation of As-contaminated paddy soil.

12.
Animals (Basel) ; 14(10)2024 May 13.
Article in English | MEDLINE | ID: mdl-38791671

ABSTRACT

In Hymenoptera, the monophyly of Evaniomorpha has been the focus of debate among different scholars. In this study, we sequenced two mitochondrial genomes of Dendrocerus (Hymenoptera: Megaspilidae) to analyze the mitochondrial genomic features of Dendrocerus and provide new molecular data for phylogenetic studies of Evaniomorpha. The mitogenome sizes of D. bellus and D. anisodontus were 15,445 bp and 15,373 bp, respectively, with the trnG of D. bellus missing. The nucleotide composition was significantly biased toward adenine and thymine, with A + T contents of 81.2% (D. bellus) and 82.4% (D. anisodontus). Using Ceraphron sp. (Ceraphronidae) as reference, the Ka/Ks values of NAD4L and NAD6 in D. anisodontus were both greater than one, indicating that non-synonymous mutations are favored by Darwinian selection, which is rare in other hymenopteran species. Compared with Ceraphon sp. gene order, nine operations were identified in D. anisodontus, including four reversals, four TDRLs (tandem duplication random losses) and one transposition, or four reversals and five TDRLs. Phylogenetic analysis of 40 mitochondrial genomes showed that Evaniomorpha was not a monophyletic group, which was also supported by the PBD values. Ceraphronoidea is a monophyletic group and is a sister to Aulacidae + Gasteruptiidae. Based on the conserved region of the newly sequenced mitochondrial genomes, a pair of specific primers MegaF/MegaR was designed for sequencing the COX1 genes in Megaspilidae and a 60% rate of success was achieved in the genus Dendrocerus.

13.
Accid Anal Prev ; 203: 107621, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38729056

ABSTRACT

The emerging connected vehicle (CV) technologies facilitate the development of integrated advanced driver assistance systems (ADASs), with which various functions are coordinated in a comprehensive framework. However, challenges arise in enabling drivers to perceive important information with minimal distractions when multiple messages are simultaneously provided by integrated ADASs. To this end, this study introduces three types of human-machine interfaces (HMIs) for an integrated ADAS: 1) three messages using a visual display only, 2) four messages using a visual display only, and 3) three messages using visual plus auditory displays. Meanwhile, the differences in driving performance across three HMI types are examined to investigate the impacts of information quantity and display formats on driving behaviors. Additionally, variations in drivers' responses to the three HMI types are examined. Driving behaviors of 51 drivers with respect to three HMI types are investigated in eight field testing scenarios. These scenarios include warnings for rear-end collision, lateral collision, forward collision, lane-change, and curve speed, as well as notifications for emergency events downstream, the specified speed limit, and car-following behaviors. Results indicate that, compared to a visual display only, presenting three messages through visual and auditory displays enhances driving performance in four typical scenarios. Compared to the presentation of three messages, a visual display offering four messages improves driving performance in rear-end collision warning scenarios but diminishes the performance in lane-change scenarios. Additionally, the relationship between information quantity and display formats shown on HMIs and driving performance can be moderated by drivers' gender, occupation, driving experience, annual driving distance, and safety attitudes. Findings are indicative to designers in automotive industries in developing HMIs for future CVs.


Subject(s)
Accidents, Traffic , Automobile Driving , Humans , Automobile Driving/psychology , Male , Female , Adult , Accidents, Traffic/prevention & control , Young Adult , User-Computer Interface , Man-Machine Systems , Automobiles , Middle Aged , Data Display
14.
J Agric Food Chem ; 72(21): 12130-12145, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38748495

ABSTRACT

Colorectal cancer (CRC) is a common malignant tumor that occurs in the colon. Gut microbiota is a complex ecosystem that plays an important role in the pathogenesis of CRC. Our previous studies showed that the soluble dietary fiber of foxtail millet (FMB-SDF) exhibited significant antitumor activity in vitro. The present study evaluated the anticancer potential of FMB-SDF in the azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced mouse CRC models. The results showed that FMB-SDF could significantly alleviate colon cancer symptoms in mice. Further, we found that FMB-SDF consumption significantly altered gut microbiota diversity and the overall structure and regulated the abundance of some microorganisms in CRC mice. Meanwhile, KEGG pathway enrichment showed that FMB-SDF can also alleviate the occurrence of colon cancer in mice by regulating certain cancer-related signaling pathways. In conclusion, our findings may provide a novel approach for the prevention and biotherapy of CRC.


Subject(s)
Bacteria , Colorectal Neoplasms , Dietary Fiber , Gastrointestinal Microbiome , Setaria Plant , Animals , Gastrointestinal Microbiome/drug effects , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/metabolism , Mice , Setaria Plant/chemistry , Dietary Fiber/metabolism , Dietary Fiber/pharmacology , Humans , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics , Bacteria/drug effects , Bacteria/metabolism , Male , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Extracts/chemistry , Azoxymethane , Mice, Inbred C57BL
15.
J Mater Chem B ; 12(21): 5157-5161, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38715545

ABSTRACT

The ability to detect and visualize cellular events and associated biological analytes is essential for the understanding of their physiological and pathological functions. Cysteine (Cys) plays a crucial role in biological systems and lysosomal homeostasis. This puts forward higher requirements on the performance of the probe. Herein, we rationally designed a coumarin-based probe for the reversible, specific, sensitive, and rapid detection of Cys based on pH regulating reactivity. The obtained probe (ECMA) introduces a morpholine moiety to target lysosomes, and α,ß-unsaturated-ketone with an electron-withdrawing CN group served as a reversible reaction site for Cys. Importantly, ECMA was successfully applied to the real-time monitoring of Cys dynamics in living cells. Furthermore, cell imaging clearly revealed that exogenous Cys could induce the up-regulation of lysosomal ROS, which provided a powerful tool for investigating the relationship between oxidative stress and lysosomal Cys.


Subject(s)
Cysteine , Fluorescent Dyes , Lysosomes , Oxidative Stress , Lysosomes/metabolism , Lysosomes/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Cysteine/chemistry , Cysteine/metabolism , Oxidative Stress/drug effects , Humans , Hydrogen-Ion Concentration , HeLa Cells , Optical Imaging , Molecular Structure , Coumarins/chemistry , Reactive Oxygen Species/metabolism
16.
Biochem Pharmacol ; 225: 116310, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38788960

ABSTRACT

Targeting the DNA damage response (DDR) is a promising strategy in oncotherapy, as most tumor cells are sensitive to excess damage due to their repair defects. Ataxia telangiectasia mutated and RAD3-related protein (ATR) is a damage response signal transduction sensor, and its therapeutic potential in tumor cells needs to be precisely investigated. Herein, we identified a new axis that could be targeted by ATR inhibitors to decrease the DNA-dependent protein kinase catalytic subunit (DNAPKcs), downregulate the expression of the retinoblastoma (RB), and drive G1/S-phase transition. Four-way DNA Holliday junctions (FJs) assembled in this process could trigger S-phase arrest and induce lethal chromosome damage in RB-positive triple-negative breast cancer (TNBC) cells. Furthermore, these unrepaired junctions also exerted toxic effects to RB-deficient TNBC cells when the homologous recombination repair (HRR) was inhibited. This study proposes a precise strategy for treating TNBC by targeting the DDR and extends our understanding of ATR and HJ in tumor treatment.

17.
J Magn Reson Imaging ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722216

ABSTRACT

BACKGROUND: Analysis of left atrial (LA) strain and left atrioventricular coupling index (LACI) have prognostic value in cardiovascular diseases. However, the prognostic value of LA strain and LACI in patients with suspected myocarditis and preserved left ventricular ejection fraction (LVEF) is unclear. PURPOSE: To investigate the prognostic value of LA strain and LACI in patients with suspected myocarditis and preserved LVEF in comparison with conventional MRI outcome predictors. STUDY TYPE: Retrospective. POPULATION: One hundred sixty-five patients with clinically suspected myocarditis and preserved LVEF with available follow-up data. FIELD STRENGTH/SEQUENCE: Steady-state free precession cine and phase-sensitive inversion recovery segmented gradient echo late gadolinium enhancement sequences at 3.0 T. ASSESSMENT: Left ventricular (LV) and LA strain were evaluated using feature tracking. LACI was calculated as the ratio of LA and LV volumes at LV end-diastole. Patients were followed-up with the primary endpoint being major adverse cardiovascular events (MACE). STATISTICAL TESTS: Independent-samples t-test and Mann-Whitney U test to compare patients with and without MACE, receiver operating characteristic (ROC) curve analysis to define high/low risk groups, Kaplan-Meier survival analysis and Cox proportional hazards regression to assess prognosis. A P value of <0.05 was considered statistically significant. RESULTS: The associations of LV strain parameters (including global radial, circumferential, and longitudinal strain) and LACI with MACE were not significant (P = 0.511, 0.108, 0.148, and 0.847, respectively). An optimal LA conduit strain (Ԑe) cutoff value of 10.4% was identified to best classify patients into low- and high-risk groups. Only Ԑe was significantly associated with MACE in both univariable (hazards ratio [HR] 0.936, 95% confidence interval [CI] 0.884-0.991) and multivariable Cox survival analyses (HR 0.937, 95% CI 0.884-0.994). DATA CONCLUSION: LA conduit strain has prognostic value in patients with suspected myocarditis and preserved LVEF, incremental to conventional MRI outcome predictors, whereas LACI was not associated with MACE occurrence. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

18.
Health Data Sci ; 4: 0125, 2024.
Article in English | MEDLINE | ID: mdl-38586197

ABSTRACT

Objective: The aim of this study is to construct a curated bibliographic dataset for a landscape analysis on Health Artificial Intelligence (HAI) research. Data Source: We integrated HAI-related bibliographic records, including publications, open research datasets, patents, research grants, and clinical trials from Medline and Dimensions. Methods: Searching: Relevant documents were identified using Medical Subject Headings (MeSH) and Field of Research (FoR) indexed by 2 bibliographic databases, Medline and Dimensions. Extracting: MeSH terms annotated from the aforementioned bibliographic databases served as the primary information for our processing. For document records lacking MeSH terms, we re-extracted them using the Medical Text Indexer (MTI). Mapping: In order to enhance interoperability, HAI multi-documents were organized using a mapping system incorporating MeSH, FoR, The International Classification of Diseases (ICD-10), and Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). Integrating: All documents were curated based on a pre-defined ontology of health problems and AI technologies from the MeSH hierarchy. Results: We collected 96,332 HAI documents (publications: 75,820, open research datasets: 638, patents: 11,226, grants: 6,113, and clinical trials: 2,535) during 2009 to 2021. On average, 75.12% of the documents were tagged with at least one label related to either health problems or AI technologies (with 92.9% of publications tagged). Summary: This study presents a comprehensive pipeline for processing and curating HAI bibliographic documents following the FAIR (Findable, Accessible, Interoperable, Reusable) standard, offering a valuable multidimensional collection for the community. This dataset serves as a crucial resource for horizontally scanning the funding, research, clinical assessments, and innovations within the HAI field.

19.
Cell Biosci ; 14(1): 51, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643205

ABSTRACT

Pain is a common symptom of many diseases with a high incidence rate. Clinically, drug treatment, as the main method to relieve pain at present, is often accompanied by different degrees of adverse reactions. Therefore, it is urgent to gain a profound understanding of the pain mechanisms in order to develop advantageous analgesic targets. The PD-L1/PD-1 pathway, an important inhibitory molecule in the immune system, has taken part in regulating neuroinflammation and immune response. Accumulating evidence indicates that the PD-L1/PD-1 pathway is aberrantly activated in various pain models. And blocking PD-L1/PD-1 pathway will aggravate pain behaviors. This review aims to summarize the emerging evidence on the role of the PD-L1/PD-1 pathway in alleviating pain and provide an overview of the mechanisms involved in pain resolution, including the regulation of macrophages, microglia, T cells, as well as nociceptor neurons. However, its underlying mechanism still needs to be further elucidated in the future. In conclusion, despite more deep researches are needed, these pioneering studies indicate that PD-L1/PD-1 may be a potential neuroimmune target for pain relief.

20.
Integr Cancer Ther ; 23: 15347354241242110, 2024.
Article in English | MEDLINE | ID: mdl-38567795

ABSTRACT

BACKGROUND: Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID. METHOD: This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis. RESULT: The RR of high-grade diarrhea and all-grade diarrhea were 0.31 (I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 (I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks. CONCLUSION: This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.


Subject(s)
Diarrhea , Humans , Irinotecan/adverse effects , Diarrhea/chemically induced , Diarrhea/prevention & control , Combined Modality Therapy
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