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1.
Int J Biol Sci ; 20(7): 2454-2475, 2024.
Article in English | MEDLINE | ID: mdl-38725854

ABSTRACT

The emergence of Poly (ADP-ribose) polymerase inhibitors (PARPi) has marked the beginning of a precise targeted therapy era for ovarian cancer. However, an increasing number of patients are experiencing primary or acquired resistance to PARPi, severely limiting its clinical application. Deciphering the underlying mechanisms of PARPi resistance and discovering new therapeutic targets is an urgent and critical issue to address. In this study, we observed a close correlation between glycolysis, tumor angiogenesis, and PARPi resistance in ovarian cancer. Furthermore, we discovered that the natural compound Paris saponin VII (PS VII) partially reversed PARPi resistance in ovarian cancer and demonstrated synergistic therapeutic effects when combined with PARPi. Additionally, we found that PS VII potentially hindered glycolysis and angiogenesis in PARPi-resistant ovarian cancer cells by binding and stabilizing the expression of RORα, thus further inhibiting ECM1 and interfering with the VEGFR2/FAK/AKT/GSK3ß signaling pathway. Our research provides new targeted treatment for clinical ovarian cancer therapy and brings new hope to patients with PARPi-resistant ovarian cancer, effectively expanding the application of PARPi in clinical treatment.


Subject(s)
Diosgenin/analogs & derivatives , Glycolysis , Neovascularization, Pathologic , Ovarian Neoplasms , Saponins , Signal Transduction , Vascular Endothelial Growth Factor Receptor-2 , Female , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Saponins/pharmacology , Saponins/therapeutic use , Signal Transduction/drug effects , Glycolysis/drug effects , Cell Line, Tumor , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/metabolism , Drug Resistance, Neoplasm/drug effects , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Animals , Mice, Nude , Mice , Angiogenesis
2.
Cell Metab ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38703762

ABSTRACT

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

3.
ACS Omega ; 9(18): 20214-20222, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38737057

ABSTRACT

Process analytical technology (PAT) has been successfully applied in numerous chemical synthesis cases and is an important tool in pharmaceutical process research and development. PAT brings new methods and opportunities for the real-time monitoring of chemical processes. In multistep synthesis, real-time monitoring of the complex reaction mixtures is a significant challenge but provides an opportunity to enhance reaction understanding and control. In this study, a combined multichannel spectrometer system with both near-infrared and Raman spectroscopy was built, and calibration models were developed to quantify the desired products, intermediates, and impurities in real-time at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating dynamic experiments in both batch and continuous-flow processes. It represents a significant step forward in data-driven, multistep pharmaceutical ingredient synthesis.

4.
Chem Biol Drug Des ; 103(5): e14556, 2024 May.
Article in English | MEDLINE | ID: mdl-38772881

ABSTRACT

Histone deacetylase 6 (HDAC6), as the key regulatory enzyme, plays an important role in the development of the nervous system. More and more studies indicate that HDAC6 has become a promising therapeutic target for CNS diseases. Herein we designed and synthesized a series of novel HDAC6 inhibitors with benzothiadiazinyl systems as cap groups and evaluated their activity in vitro and in vivo. Among them, compound 3 exhibited superior selective inhibitory activity against HDAC6 (IC50 = 5.1 nM, about 30-fold selectivity over HDAC1). The results of docking showed that compound 3 can interact well with the key amino acid residues of HDAC6. Compound 3 showed lower cytotoxicity (20 µM to SH-SY5Y cells, inhibition rate = 25.75%) and better neuroprotective activity against L-glutamate-induced SH-SY5Y cell injury model in vitro. Meanwhile, compound 3 exhibited weak cardiotoxicity (10 µM hERG inhibition rate = 17.35%) and possess good druggability properties. Especially, compound 3 could significantly reduce cerebral infarction from 49.87% to 32.18%, and similar with butylphthalide in MCAO model, indicating potential clinical application prospects for alleviating ischemic stroke-induced brain infarction.


Subject(s)
Drug Design , Histone Deacetylase 6 , Histone Deacetylase Inhibitors , Molecular Docking Simulation , Neuroprotective Agents , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/chemistry , Humans , Histone Deacetylase 6/antagonists & inhibitors , Histone Deacetylase 6/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/chemical synthesis , Animals , Structure-Activity Relationship , Cell Line, Tumor , Male , Mice , Binding Sites , Rats
5.
Inorg Chem ; 63(22): 10108-10113, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38771149

ABSTRACT

Metal-organic cages (MOCs) with luminophores have significant advantages for the facile detection of specific molecules based on turn-on or turn-off luminescence changes induced by host-guest complexation. One important challenge is the development of turn-on-type near-infrared (NIR)-luminescent MOCs. In this study, we synthesized a novel MOC consisting of two porphyrin dyes linked by four Yb(III) complexes, which exhibit bimodal red and NIR fluorescence signals upon photoexcitation of the porphyrin π system. Single-crystal X-ray structural analysis and computational molecular modeling revealed that planar aromatic perfluorocarbons were intercalated into the MOC. The tight packing between the MOC and guests enhanced the NIR fluorescence of Yb(III) by suppressing energy transfer from the photoexcited porphyrin to oxygen molecules. Guest-responsive turn-on NIR fluorescence changes in an MOC were successfully demonstrated.

6.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1924-1931, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812205

ABSTRACT

The Chinese medical mechanism of Huanglian Jieduo Decoction on treating Alzheimer's disease(AD) characterized by "toxin damaging brain collateral" is still unclear. This study aims to explore the mechanism of Huanglian Jieduo Decoction on regulating triggering receptor expressed on myeloid cells 2(TREM2)/protein kinase B(Akt)/glycogen synthase kinase 3ß(GSK3ß) pathway to improve the cognitive deficit in APP/PS1 transgenic mice. APP/PS1 mice of approximately nine months old were randomly divided into the model group, the low, medium, and high(2.5, 5, and 10 g·kg~(-1)) groups of Huanglian Jiedu Decoction, and 0.75 mg·kg~(-1) donepezil hydrochloride group, and the C57BL/6J mice with the same age were taken as the normal group. After one month of continuous oral administration, a Morris water maze was performed to detect the learning and memory ability of mice. Hematoxylin-eosin(HE) staining was applied to observe the morphology of neuronal cells in the cortical area of mice. Immunofluorescence was used to detect the protein expressions of ß-amyloid(Aß_(1-42)), CD86, and arginase 1(Arg1). The mRNA levels of interleukin(IL)-1ß, IL-6, and IL-10 in the cortex of mice were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expressions of TREM2, phosphoinositide-3 kinase(PI3K), Akt, GSK3ß, and beta-catenin(ß-catenin) in mouse cortex were determined by Western blot. The results indicated that the escape latency of the model group was significantly prolonged, and the residence time in the target quadrant and the number of crossing the platform were significantly reduced compared with the normal group. Mice in the model group had a significantly lower number of neurons in the cortex and showed nuclear pyknosis and a significant increase in the expressions of Aß_(1-42) and CD86. The mRNA levels of IL-1ß and IL-6 in tissue were significantly increased, IL-10 were increased, while Arg1 were significantly decreased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin in the cortex were significantly down-regulated. Compared with the model group, the escape latency of the mice in the administration group was significantly shortened, and the number of crossing the platform and the residence time in the target quadrant were significantly increased. Furthermore, the number of neurons in the cortex of mice was increased, and nuclear pyknosis was improved. Aß_(1-42) deposition was decreased significantly. The mRNA levels of IL-1ß, IL-6 and CD86 were significantly decreased, while IL-10 and Arg1 levels were significantly increased. The expression of TREM2, p-PI3K(Y607), p-Akt(T308), p-GSK3ß(Ser9), and ß-catenin protein in the cortex of each administration group was significantly up-regulated compared with the model group. In conclusion, Huanglian Jiedu Decoction reduced the expression of Aß_(1-42) and neuroinflammation to a neuro-protective effect, thereby improving the learning and memory ability in APP/PS1 mice, which may be related to the TREM2/Akt/GSK3ß signaling pathway.


Subject(s)
Alzheimer Disease , Cerebral Cortex , Drugs, Chinese Herbal , Glycogen Synthase Kinase 3 beta , Membrane Glycoproteins , Mice, Inbred C57BL , Mice, Transgenic , Proto-Oncogene Proteins c-akt , Receptors, Immunologic , Animals , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Mice , Cerebral Cortex/metabolism , Cerebral Cortex/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/genetics , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Male , Signal Transduction/drug effects , Humans
7.
Angew Chem Int Ed Engl ; : e202405584, 2024 May 26.
Article in English | MEDLINE | ID: mdl-38797714

ABSTRACT

Large dissymmetry factor of the circularly polarized luminescence (gCPL) was observed in ligand and coordination tuned chiral tetrakis europium (Eu(III)) complexes with ammonium cations. The gCPL value was estimated to be -1.54, which is the largest among chiral luminescent molecules. Through photophysical measurements, single crystal X-ray structural analyses and quantum chemical calculations, changes in the geometric and electronic structures were observed for a series of chiral tetrakis Eu(III) complexes which enhanced the gCPL value. The emission quantum yield and photosensitized energy transfer efficiencies of chiral Eu(III) complexes with ammonium cations were also larger than that with previous Cs+. Based on the systematic modifications and analyses for chiral tetrakis Eu(III) complex, effect of the ammonium cation on enhanced CPL brightness is reported.

8.
Sensors (Basel) ; 24(7)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38610529

ABSTRACT

Intelligent vehicle trajectory tracking exhibits problems such as low adaptability, low tracking accuracy, and poor robustness in complex driving environments with uncertain road conditions. Therefore, an improved method of adaptive model predictive control (AMPC) for trajectory tracking was designed in this study to increase the corresponding tracking accuracy and driving stability of intelligent vehicles under uncertain and complex working conditions. First, based on the unscented Kalman filter, longitudinal speed, yaw speed, and lateral acceleration were considered as the observed variables of the measurement equation to estimate the lateral force of the front and rear tires accurately in real time. Subsequently, an adaptive correction estimation strategy for tire cornering stiffness was designed, an AMPC method was established, and a dynamic prediction time-domain adaptive model was constructed for optimization according to vehicle speed and road adhesion conditions. The improved AMPC method for trajectory tracking was then realized. Finally, the control effectiveness and trajectory tracking accuracy of the proposed AMPC technique were verified via co-simulation using CarSim and MATLAB/Simulink. From the results, a low lateral position error and heading angle error in trajectory tracking were obtained under different vehicle driving conditions and road adhesion conditions, producing high trajectory-tracking control accuracy. Thus, this work provides an important reference for improving the adaptability, robustness, and optimization of intelligent vehicle tracking control systems.

9.
Med Rev (2021) ; 4(2): 129-153, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38680680

ABSTRACT

In the field of biomedical research, organoids represent a remarkable advancement that has the potential to revolutionize our approach to studying human diseases even before clinical trials. Organoids are essentially miniature 3D models of specific organs or tissues, enabling scientists to investigate the causes of diseases, test new drugs, and explore personalized medicine within a controlled laboratory setting. Over the past decade, organoid technology has made substantial progress, allowing researchers to create highly detailed environments that closely mimic the human body. These organoids can be generated from various sources, including pluripotent stem cells, specialized tissue cells, and tumor tissue cells. This versatility enables scientists to replicate a wide range of diseases affecting different organ systems, effectively creating disease replicas in a laboratory dish. This exciting capability has provided us with unprecedented insights into the progression of diseases and how we can develop improved treatments. In this paper, we will provide an overview of the progress made in utilizing organoids as preclinical models, aiding our understanding and providing a more effective approach to addressing various human diseases.

10.
Phytochemistry ; 222: 114100, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38636688

ABSTRACT

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.


Subject(s)
Artemisia , Artemisia/chemistry , Humans , Molecular Structure , Structure-Activity Relationship , Sesquiterpenes, Guaiane/chemistry , Sesquiterpenes, Guaiane/pharmacology , Sesquiterpenes, Guaiane/isolation & purification , Animals , Dimerization , Molecular Docking Simulation , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Sesquiterpenes/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor
11.
Dalton Trans ; 53(20): 8555-8562, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38567493

ABSTRACT

Photosensitizer design of luminescent terbium (Tb(III)) complexes with narrow bandwidths is important for advancing luminescent materials. In this study, we report an effective photosensitizer model in a thermally populated lowest excited triplet (T1) state during Tb(III) emission. The Tb(III) complex comprises a Tb(III) ion (serving as an emission center), hexafluoroacetylacetonates (acting as photosensitizer ligands), and bulky cyclohexyl group-attached phosphine-oxide-type ligands (functioning as an oxygen barrier system). Emission properties including emission and excitation spectra, ligand-excited emission quantum yields, and emission lifetimes were evaluated in the absence and presence of oxygen. Coordination geometry structures were determined through analysing single-crystal structures. The electronic structure based on 4f-orbitals was estimated from radiative rate constants and quantum chemical calculations. The bulky phosphine oxide ligand not only provides an oxygen barrier system but also induces an electronic structural modulation based on 4f-orbitals, allowing for effective photosensitized Tb(III) emission in a thermally populated ligand T1 state in air.

12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 201-206, 2024 Feb 15.
Article in Chinese | MEDLINE | ID: mdl-38436320

ABSTRACT

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, and its etiology and pathogenesis are still unclear. Brain is the organ with the largest oxygen consumption in human body and is easily affected by oxidative imbalance. Oxidative stress has become the key research direction for the pathogenesis of ADHD, but there is still a lack of relevant studies in China. Based on the latest research findings in China and overseas, this article reviews the clinical and experimental studies on oxidative stress in ADHD and explores the association of oxidative stress with neurotransmitter imbalance, neuroinflammation, and cell apoptosis in the pathogenesis of ADHD, so as to provide new research ideas for exploring the pathogenesis of ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Adolescent , Child , Humans , Attention Deficit Disorder with Hyperactivity/etiology , Oxidative Stress , Apoptosis , Brain , China
13.
Chem Asian J ; 19(7): e202400038, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38348520

ABSTRACT

Luminescent molecule-based bioimaging system is widely used for precise localization and distinction of cancer/tumor cells. Luminescent lanthanide (Ln(III)) complexes offer long-lived (sub-millisecond time scale) and sharp (FWHM <10 nm) emission, arising from the forbidden 4f-4f electronic transitions. Luminescent Ln(III) complex-based bioimaging has emerged as a promising option for both in vitro and in vivo visualizations. In this mini-review, the historical development and recent significant progress of luminescent Ln(III) probes for bioapplications are introduced. The recent studies are mainly focused on three points: (i) the structural modifications of Ln(III) complexes in both macrocyclic and small ligands, (ii) the acquirement of high resolution luminescence images of cancer/tumor cells and (iii) the constructions of ratiometric biosensors. Furthermore, our recent study is explained as a new Cancer GPS (cancer grade probing for determining tumor grade through photophysical property analyses of intracellular Eu(III) complex.


Subject(s)
Biosensing Techniques , Lanthanoid Series Elements , Neoplasms , Humans , Lanthanoid Series Elements/chemistry , Luminescence , Ligands , Neoplasms/diagnostic imaging
14.
J Exp Clin Cancer Res ; 43(1): 54, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383447

ABSTRACT

BACKGROUND: LATS1/2 are frequently mutated and down-regulated in endometrial cancer (EC), but the contributions of LATS1/2 in EC progression remains unclear. Impaired antigen presentation due to mutations or downregulation of the major histocompatibility complex class I (MHC-I) has been implicated in tumor immune evasion. Herein, we elucidate the oncogenic role that dysregulation of LATS1/2 in EC leads to immune evasion through the down-regulation of MHC-I. METHODS: The mutation and expression as well as the clinical significance of LATS1/2 in EC was assessed in the TCGA cohort and our sample cohort. CRISPR-Cas9 was used to construct knockout cell lines of LATS1/2 in EC. Differentially expressed genes were analyzed by RNA-seq. The interaction between LATS1/2 and STAT1 was verified using co-immunoprecipitation and GST pull-down assays. Mass spectrometry, in vitro kinase assays, ChIP-qPCR, flow cytometry, immunohistochemistry, immunofluorescence and confocal microscopy were performed to investigate the regulation of LATS1/2 on MHC-I through interaction with and phosphorylate STAT1. The killing effect of activated PBMCs on EC cells were used to monitor anti-tumor activity. RESULTS: Here, we demonstrate that LATS1/2 are frequently mutated and down-regulated in EC. Moreover, LATS1/2 loss was found to be associated with a significant down-regulation of MHC-I, independently of the Hippo-YAP pathway. Instead, LATS1/2 were found to directly interact with and phosphorylate STAT1 at Ser727, a crucial transcription factor for MHC-I upregulation in response to interferon-gamma (IFN-γ) signaling, to promote STAT1 accumulating and moving into the nucleus to enhance the transcriptional activation of IRF1/NLRC5 on MHC-I. Additionally, the loss of LATS1/2 was observed to confer increased resistance of EC cells to immune cell-mediated killing and this resistance could be reversed by over-expression of MHC-I. CONCLUSION: Our findings indicate that dysregulation of LATS1/2 in EC leads to immune evasion through the down-regulation of MHC-I, leading to the suppression of infiltrating activated CD8 + T cells and highlight the importance of LATS1/2 in IFN-γ signaling-mediated tumor immune response, suggesting that LATS1/2 is a promising target for immune checkpoint blockade therapy in EC.


Subject(s)
Endometrial Neoplasms , Tumor Escape , Female , Humans , Histocompatibility Antigens Class I , Antigen Presentation , Protein Serine-Threonine Kinases/genetics , Endometrial Neoplasms/genetics , Intracellular Signaling Peptides and Proteins
15.
PLoS Pathog ; 20(2): e1011999, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38306394

ABSTRACT

Hepatitis B virus (HBV) chronically infects 296 million people worldwide, posing a major global health threat. Export of HBV RNAs from the nucleus to the cytoplasm is indispensable for viral protein translation and genome replication, however the mechanisms regulating this critical process remain largely elusive. Here, we identify a key host factor embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) that binds HBV RNAs and controls their nuclear export. Using an unbiased quantitative proteomics screen, we demonstrate direct binding of ELAVL1 to the HBV pregenomic RNA (pgRNA). ELAVL1 knockdown inhibits HBV RNAs posttranscriptional regulation and suppresses viral replication. Further mechanistic studies reveal ELAVL1 recruits the nuclear export receptor CRM1 through ANP32A and ANP32B to transport HBV RNAs to the cytoplasm via specific AU-rich elements, which can be targeted by a compound CMLD-2. Moreover, ELAVL1 protects HBV RNAs from DIS3+RRP6+ RNA exosome mediated nuclear RNA degradation. Notably, we find HBV core protein is dispensable for HBV RNA-CRM1 interaction and nuclear export. Our results unveil ELAVL1 as a crucial host factor that regulates HBV RNAs stability and trafficking. By orchestrating viral RNA nuclear export, ELAVL1 is indispensable for the HBV life cycle. Our study highlights a virus-host interaction that may be exploited as a new therapeutic target against chronic hepatitis B.


Subject(s)
Hepatitis B virus , RNA, Viral , Animals , Humans , Hepatitis B virus/metabolism , Active Transport, Cell Nucleus , RNA, Viral/genetics , RNA, Viral/metabolism , Drosophila/genetics , Virus Replication/genetics , Nuclear Proteins/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , ELAV-Like Protein 1/genetics , ELAV-Like Protein 1/metabolism
16.
Quant Imaging Med Surg ; 14(2): 1369-1382, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38415142

ABSTRACT

Background: Atrial fibrillation (AF) has been identified to increase stroke risk, even after oral anticoagulants (OACs), and the recurrence rate is high after radiofrequency catheter ablation (RFCA). Inflammation is an essential factor in the occurrence and persistence of AF. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is an established molecular imaging modality to detect local inflammation. We aimed to investigate the relationship between atrial inflammatory activity and poor prognosis of AF based on 18F-FDG PET/CT. Methods: A total of 204 AF patients including 75 with paroxysmal AF (ParAF) and 129 with persistent AF (PerAF) who underwent PET/CT before treatment were enrolled in this prospective cohort study. Clinical data, electrocardiograph (ECG), echocardiography, and cardiac 18F-FDG uptake were collected. Follow-up information was obtained from patient clinical case notes or telephone reviews, with the starting point being the time of PET/CT scan. The follow-up deadline was either the date of AF recurrence after RFCA, new-onset stroke, or May 2023. Cox proportional hazards regression models were used to identify predictors of poor prognosis and hazard ratios (HRs) with 95% confidence intervals (CIs) was calculated. Results: Median follow-up time was 29 months [interquartile range (IQR), 22-36 months]. Poor prognosis occurred in 52 patients (25.5%), including 34 new-onset stroke patients and 18 recrudescence after RFCA. The poor prognosis group had higher congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (TIA) or thromboembolism (doubled), vascular disease, age 65-74 years, sex category (female) (CHA2DS2-VASc) score [3.0 (IQR, 1.0-3.75) vs. 2.0 (IQR, 1.0-3.0), P=0.01], right atrial (RA) wall maximum standardized uptake value (SUVmax) (4.13±1.82 vs. 3.74±1.58, P=0.04), higher percentage of PerAF [39 (75.0%) vs. 90 (59.2%), P=0.04], left atrial (LA) enlargement [45 (86.5%) vs. 104 (68.4%), P=0.01], and RA wall positive FDG uptake [40 (76.9%) vs. 79 (52.0%), P=0.002] compared with the non-poor prognosis group. Univariate and multivariate Cox proportional hazard regression analysis concluded that only CHA2DS2-VASc score (HR, 1.29; 95% CI: 1.06-1.57; P=0.01) and RA wall positive FDG uptake (HR, 2.68; 95% CI: 1.10-6.50; P=0.03) were significantly associated with poor prognosis. Conclusions: RA wall FDG positive uptake based on PET/CT is tightly related to AF recurrence after RFCA or new-onset stroke after antiarrhythmic and anticoagulation treatment.

17.
Sci Rep ; 14(1): 778, 2024 01 22.
Article in English | MEDLINE | ID: mdl-38253656

ABSTRACT

Accurate determination of human tumor malignancy is important for choosing efficient and safe therapies. Bioimaging technologies based on luminescent molecules are widely used to localize and distinguish active tumor cells. Here, we report a human cancer grade probing system (GPS) using a water-soluble and structure-changeable Eu(III) complex for the continuous detection of early human brain tumors of different malignancy grades. Time-dependent emission spectra of the Eu(III) complexes in various types of tumor cells were recorded. The radiative rate constants (kr), which depend on the geometry of the Eu(III) complex, were calculated from the emission spectra. The tendency of the kr values to vary depended on the tumor cells at different malignancy grades. Between T = 0 and T = 3 h of invasion, the kr values exhibited an increase of 4% in NHA/TS (benign grade II gliomas), 7% in NHA/TSR (malignant grade III gliomas), and 27% in NHA/TSRA (malignant grade IV gliomas). Tumor cells with high-grade malignancy exhibited a rapid upward trend in kr values. The cancer GPS employs Eu(III) emissions to provide a new diagnostic method for determining human brain tumor malignancy.


Subject(s)
Brain Neoplasms , Glioma , Humans , Brain Neoplasms/diagnostic imaging , Brain , Luminescence , Records
18.
J Orthop Surg Res ; 19(1): 100, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38297319

ABSTRACT

BACKGROUND: There are many predictions about the progression of natural collapse course of osteonecrosis of the femoral head. Here, we aimed to combine the three classical prediction methods to explore the progression of the natural collapse course. METHODS: This retrospective study included 127 patients admitted to our hospital from October 2016 to October 2017, in whom the femoral head had not collapsed. Logistic regression analysis was performed to determine the collapse risk factors, and Kaplan-Meier survival curves were used for femoral head survival analysis. The collapse rate of the femoral head was recorded within 5 years based on the matrix model. The specificity of the matrix model was analyzed using the receiver operating characteristic curve. RESULTS: A total of 127 patients with a total of 202 hips were included in this study, and 98 hips collapsed during the follow-up period. Multivariate logistics regression analysis showed that the predictive ability of the matrix model was stronger than Association Research Circulation Osseous staging, Japanese Investigation Committee classification, and area (P < 0.05). Kaplan-Meier survival curve showed that the median survival time of femoral head in patients was 3 years. The result of the receiver operating characteristic curve analysis showed that the area under the curve (AUC) of the matrix model had better predictive value (AUC = 0.771, log-rank test: P < 0.001). CONCLUSION: We creatively combined the three classical prediction methods for evaluating the progression of the natural collapse course based on the matrix model and found that the higher the score of the matrix model, the higher the femoral head collapse rate. Specifically, the matrix model has a potential value in predicting femoral head collapse and guiding treatment selection.


Subject(s)
Femur Head Necrosis , Femur Head , Humans , Femur Head/diagnostic imaging , Femur Head Necrosis/diagnostic imaging , Femur Head Necrosis/etiology , Retrospective Studies , Hip , Risk Factors
19.
J Orthop Surg Res ; 18(1): 783, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37853426

ABSTRACT

OBJECTIVE: This aimed to evaluate the status of return to work (RTW) in patients with osteonecrosis of the femoral head (ONFH) after total hip arthroplasty (THA). METHODS: The baseline characteristics of all patients in this retrospective study were obtained from the hospital patient database. The relevant changes in patients' working conditions, as well as the numerical rating scale (NRS), Harris Hip Score (HHS), self-assessment of work ability, and Likert scale satisfaction assessment were obtained through video call follow-ups. RESULTS: 118 patients (response rate: 83%) were ultimately included in this study. The average length of time for the patients to stop working preoperatively was 20.7 weeks. Ninety-four patients (24 women and 70 men) who underwent THA had RTW status, with a mean RTW time of 21.0 weeks. Men had a significantly higher proportion of final RTW and a significantly faster RTW than women. Significant differences in smoking, drinking, cardiovascular diseases, changes in working levels, variations in the types of physical work, changes in working hours, and pain symptoms were observed between the RTW and Non-RTW populations. The patients with a positive RTW status had higher postoperative HHS scores, lower postoperative NRS scores, and higher self-assessment of work ability than patients who had a negative RTW status. CONCLUSION: Ultimately, 80% of patients achieved RTW status. Drinking, sex, change in working level, variation in the type of physical work, change in working hours, post-surgery HHS score and self-assessment of work ability can serve as predictive factors for RTW.


Subject(s)
Arthroplasty, Replacement, Hip , Femur Head Necrosis , Male , Humans , Female , Arthroplasty, Replacement, Hip/adverse effects , Return to Work , Retrospective Studies , Femur Head/surgery , Femur Head Necrosis/surgery , Treatment Outcome
20.
J Mater Chem B ; 11(36): 8818, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37674465

ABSTRACT

Correction for 'A novel PEC and ECL bifunctional aptasensor based on V2CTx MXene-derived MOF embedded with silver nanoparticles for selectively aptasensing miRNA-126' by Yu Li et al., J. Mater. Chem. B, 2023, https://doi.org/10.1039/d3tb01380d.

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