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1.
Biol Res Nurs ; : 10998004241288791, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39378890

ABSTRACT

OBJECTIVE: To explore the relationship between the high frequency (HF) heart rate variability (HRV) and electroencephalogram (EEG) delta band power in women with irritable bowel syndrome (IBS) versus healthy control women. MATERIALS AND METHODS: Twenty women with IBS and twenty healthy controls were studied over three consecutive nights using polysomnography in a sleep laboratory. To avoid the first night effect, only second-night data were analyzed. Power spectral analysis was applied to HRV and EEG recordings. The linear system coherence/phase analysis assessed the relationship between normalized HF power of HRV and normalized delta band power of EEG during the first four NREM-REM sleep cycles. RESULTS: Women with IBS exhibited a significantly higher percentage of NREM sleep, higher normalized HF, lower normalized low frequency (LF) and decreased LF/HF ratio of HRV in the first four NREM-REM sleep cycles compared to controls. Additionally, their normalized delta band power was significantly lower in these sleep cycles and over the whole night. The phase shift between HF and delta band power was significantly longer in the IBS group. While the coherence between normalized HF and normalized delta band power was lower in the IBS group, the difference was not statistically significant. CONCLUSIONS: The coherence/phase analysis showed a dysregulated interaction between autonomic and central nervous systems in women with IBS, manifested by increased lag time between cardiac and EEG delta band power compared to healthy controls. Whether this dysregulation contributes to the pathophysiology of IBS remains to be determined.

2.
Front Med (Lausanne) ; 11: 1443596, 2024.
Article in English | MEDLINE | ID: mdl-39380735

ABSTRACT

Background: Infections in patients with hematological malignancies (HM) are a significant cause of morbidity and mortality. Timely and effective empirical anti-infective treatment can reduce the infection-related mortality rate. Targeted next-generation sequencing (tNGS) offers a rapid diagnostic approach for identifying diverse pathogens in these patients. However, relevant research is still limited to adult patients with HM. Methods: We conducted a retrospective analysis of adult HM patients admitted to our hospital from March 2023 to September 2023, focusing on their clinical characteristics and the results of both tNGS and conventional microbiological tests (CMTs). We evaluated the performance of tNGS and CMTs in pathogenic diagnosis and described the distribution characteristics of pathogens in adult HM patients with infections. Results: The study included 209 samples collected from 137 patients. Results showed that the overall pathogen detection rate differed significantly between tNGS and CMTs (60.3% vs. 24.4%, p < 0.001). The sensitivity (69.7% vs. 35.9%), negative predictive value (NPV) (48.2% vs. 42.4%), and accuracy (66.5% vs. 56.5%) of pathogen detection were notably superior with tNGS compared to CMTs. Among the 142 samples with clinically diagnosed infections, tNGS combined with CMTs identified a definite or probable microbial etiology in 114 samples (80.3%). Of the 36 samples with concordant positive results from both tNGS and CMTs, 72.2% (26/36) exhibited full or partial agreement. Our study further showed the highest detection rate for viral infections (57.0%), predominantly for Epstein-Barr virus (DNA-V, 18.3%). Followed by bacterial infections (46.5%), the detection rate of Gram-negative bacteria (G+, 35.9%) was higher than that of Gram-positive bacteria (G-, 21.8%) in this study. Klebsiella pneumoniae (G-, 12.7%) had the highest detection rate among these emerging bacteria, followed by Pseudomonas aeruginosa (G-, 10.6%) and Enterococcus faecium (G+, 7.7%). Bacterial-viral coinfections were the most common type of mixed infection (35.5%). Conclusion: In conclusion, tNGS outperforms CMTs in both sensitivity and pathogen spectrum. Therefore, it can serve as an adjunct to CMTs to facilitate the precise adjustment of anti-infective regimens for adult HM patients. Our findings establish a basis for formulating empirical anti-infective therapy strategies tailored to the pathogen distribution in this patient population.

3.
Int J Biol Macromol ; 279(Pt 4): 135476, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39260646

ABSTRACT

Cellulose nanofiber (CNF) has been widely used in MXene film electrodes to improve its mechanical properties and rate capability for supercapacitors. However, all the above enhancements are obtained with inevitably sacrificing the capacitance, because of the non-electrochemically-active characteristic of CNF. Herein, to address this issue, lignin-containing cellulose fibers (LCNF) is innovatively used to substitute CNF. Specifically, LCNF play a role as a bridge to significantly reinforce mechanical strength of LCNF/MXene film electrode (LM) by binding the adjacent MXene nanosheets, reaching a tensile strength of 34.2 MPa. Lignin in LCNF contributes to pseudocapacitance through the reversible conversion of its quinone/hydro-quinone (Q/QH2), thus yielding an excellent capacitance of 364.4 F g-1 at 1 A g-1. Meanwhile, LCNF has different diameters in which microfibers form a loose structure for LM, nanofibers enlarge d-spacing between adjacent MXene nanosheets, and fibers self-crosslinking creates abundant pores, thus constructing graded channels to achieve an outstanding rate capability of 87 % at 15 A g-1. The fabricated supercapacitor demonstrates a large energy density of 1.8 Wh g-1 at 71.3 W g-1. This work provides a promising approach to decouple the trade-off between electrochemical performance and mechanical properties of MXene film electrodes caused by using CNF, thus obtaining high-performance supercapacitors.


Subject(s)
Cellulose , Electric Capacitance , Electrodes , Lignin , Nanofibers , Lignin/chemistry , Cellulose/chemistry , Nanofibers/chemistry , Tensile Strength
4.
J Robot Surg ; 18(1): 347, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39313734

ABSTRACT

Total hip arthroplasty (THA) effectively treats various end-stage hip conditions, offering pain relief and improved joint function. However, surgical outcomes are influenced by multifaceted factors. This research aims to create a predictive model, incorporating radiomic and clinical information, to forecast post-surgery joint function in robot-assisted THA (RA-THA) patients. The study set comprised 136 patients who underwent unilateral RA-THA, which were subsequently partitioned into a training set (n = 95) and a test set (n = 41) for analysis. Preoperative CT imaging was employed to derive 851 radiomic characteristics, selecting those with an intra-class correlation coefficient > 0.75 for analysis. Least absolute shrinkage and selection operator regression reduced redundancy to six significant radiomic features. Clinical data including preoperative Visual Analog Scale (VAS), Harris Hip Score (HHS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score were collected. Logistic regression identified significant predictors, and three models were developed. Receiver operating characteristic and decision curves evaluated the models. Preoperative VAS, HHS, WOMAC score, and radiomics feature scores were significant predictors. In the training set, the AUCs were 0.835 (clinical model), 0.757 (radiomic model), and 0.891 (combined model). In the test set, the AUCs were 0.777 (clinical model), 0.824 (radiomic model), and 0.881 (combined model). The constructed nomogram prediction model combines radiological features with relevant clinical data to accurately predict functional outcomes 3 years after RA-THA. This model has significant prediction accuracy and broad clinical application prospects and can provide a valuable reference for formulating personalized treatment plans and optimizing patient management strategies.


Subject(s)
Arthroplasty, Replacement, Hip , Robotic Surgical Procedures , Humans , Arthroplasty, Replacement, Hip/methods , Robotic Surgical Procedures/methods , Male , Female , Middle Aged , Aged , Hip Joint/diagnostic imaging , Hip Joint/surgery , Hip Joint/physiopathology , Tomography, X-Ray Computed/methods , Postoperative Period , Treatment Outcome , ROC Curve , Radiomics
5.
Front Pharmacol ; 15: 1436013, 2024.
Article in English | MEDLINE | ID: mdl-39329120

ABSTRACT

Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication in patients with diabetes mellitus. Necroptosis is regarded as a form of cell death that is intimately associated with the inflammatory response, which is not only initiated by inflammatory factors such as TNF-α, but also triggers the inflammatory cascade through the rupture of the dying cell. There is no definitive study on the role of necroptosis in the pathological process of DMED. In light of the pathological features of high inflammation levels in DMED patients, we assessed whether the necroptosis plays an important role in the course of DMED. Our study revealed that penile tissues of DMED rats showed high levels of key necroptosis factors such as receptor-interacting protein kinase 3 (RIP3), mixed-lineage kinase domain-like protein (MLKL), and transient receptor potential melatonin 7 (TRPM7). Furthermore, the inhibition of necroptosis with a receptor-interacting protein kinase 3 (RIP3) inhibitor or Yimusake (a common herbal remedy for ED) effectively rescued damage to corpus cavernosum smooth muscle cells (CCSMC) under high glucose conditions. Our findings suggest that inhibition of the RIP3/MLKL/TRPM7 necroptotic pathway could effectively ameliorate CCSMCs fibrosis and death induced by high glucose and inhibited the inflammatory response.

6.
Adv Mater ; : e2407826, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39313982

ABSTRACT

The extended use of androgen deprivation therapy (ADT) may often lead to the progression from castration-sensitive prostate cancer (CSPC) to castration-resistant prostate cancer (CRPC) in prostate cancer. To address this, it is essential to inhibit the nuclear translocation of the androgen receptor (AR) as part of an effective disease-modifying strategy. Microtubules play a central role in facilitating AR nuclear translocation, highlighting their importance as a therapeutic target. In this regard, a designated as the targeted microtubules transformable nanopeptide system (MTN) is developed. This system is designed to disrupt microtubule structure and function through dual-targeting of prostate-specific membrane antigen (PSMA) and ß-tubulin. Initially, MTN targets prostate cells via PSMA and then specifically binds to ß-tubulin within microtubules, leading to the formation of nanofibers. These nanofibers subsequently induce the polymerization of microtubules, thereby disrupting AR transport. Notably, MTN exhibits efficient and prolonged suppression of prostate cancer across the spectrum from CSPC to CRPC, with a highly favorable safety profile in normal cells. These findings highlight the potential of MTN as a novel and promising approach for comprehensive prostate cancer therapy throughout its entire progression.

7.
Adv Healthc Mater ; : e2401724, 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39324547

ABSTRACT

Mesenchymal stem cell (MSC)-based therapies show potential to treat ischemic diseases owing to their versatile functions. However, sustaining MSC viability and therapeutic efficacy in ischemic tissues postengraftment remains a significant challenge. This is because, although MSCs are metabolically flexible, they fail to adapt to hypoxic conditions in the absence of glucose, leading to cell death. To overcome these issues, it is aimed to establish an injectable glucose delivery system using starch and amyloglucosidase embedded in alginate microgels. Here, starch/amyloglucosidase (S/A) microgels are engineered to continuously release glucose for seven days via enzymatic hydrolysis, thereby supporting MSC functions under ischemic conditions. In vitro tests under oxygen/glucose-deprived conditions revealed that the S/A microgels not only maintained the viability and intracellular energy but also enhanced the pro-angiogenic and immunomodulatory functions of MSCs. In vivo data further confirmed the pro-survival and pro-angiogenic effects of S/A microgels on MSCs following subcutaneous engraftment in mice. Overall, the developed S/A microgel significantly enhanced the survival and therapeutic potential of MSCs via sustained glucose delivery, highlighting its potential use in advancing MSC-based therapies for ischemic conditions.

8.
J Bone Miner Metab ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39325234

ABSTRACT

OBJECTIVE: This study aimed to estimate the relation between cigarette smoking and hip fracture in men compared with women using a meta-analytic approach. METHODS: On March 1, 2024, prospective cohort studies were searched from PubMed, Embase and Cochrane library systems. The gender difference in the relationship between smoking and hip fracture risk was evaluated by random effect model. RESULTS: Eleven prospective cohort studies involving data from 2,689,620 individuals were selected for meta-analysis. The ratio of relative risk (RRR) of hip fractures in current smokers was significantly higher in men than in women (RRR: 1.10; 95%CI: 1.00 - 1.20; P = 0.047), while no evidence of sex differences in former smoking and hip fracture risk (RRR: 0.98; 95%CI: 0.88 - 1.10; P = 0.759). CONCLUSIONS: The male-to-female RRR of hip fractures increased in current smokers, whereas no sex difference was found in the relationship between former smoking and the risk of hip fractures.

9.
Trends Ecol Evol ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39242333

ABSTRACT

Group-living animals sleep together, yet most research treats sleep as an individual process. Here, we argue that social interactions during the sleep period contribute in important, but largely overlooked, ways to animal groups' social dynamics, while patterns of social interaction and the structure of social connections within animal groups play important, but poorly understood, roles in shaping sleep behavior. Leveraging field-appropriate methods, such as direct and video-based observation, and increasingly common on-animal motion sensors (e.g., accelerometers), behavioral indicators can be tracked to measure sleep in multiple individuals in a group of animals simultaneously. Sleep proximity networks and sleep timing networks can then be used to investigate the collective dynamics of sleep in wild group-living animals.

10.
Front Oncol ; 14: 1460566, 2024.
Article in English | MEDLINE | ID: mdl-39296983

ABSTRACT

Background: Benign tumors of the spleen are rare compared to those of other parenchymal organs, accounting for less than 0.007% of all tumors, and are often found incidentally. Splenolymphangiomas are much rarer, commonly occur in children, and tend to have multiple foci. Splenic lymphangiomas are rare in adults, and fewer than 20 adult patients with isolated splenic lymphangiomas have been reported. In this article, we report the case of a middle-aged female patient with isolated splenic lymphangioma who underwent laparoscopic anatomical hypophysectomy of the lower pole of the spleen. We also summarize the existing literature on splenic lymphangioma diagnosis and available treatment options. Case presentation: A 58-year-old middle-aged woman was found to have a mass approximately 60 mm in diameter at the lower pole of the spleen during a health checkup that was not accompanied by other symptoms or examination abnormalities. After completing a preoperative examination with no contraindications to surgery, the patient underwent laparoscopic anatomical splenectomy of the lower extremity of the spleen. The patient recovered well without complications and was discharged from the hospital on the 7th postoperative day. Histopathological and immunohistochemical results confirmed the diagnosis of splenic lymphangioma. Prompt surgical intervention is safe and necessary when splenic lymphangiomas are large or associated with a risk of bleeding. Conclusion: Splenic lymphangiomas are rare and require early surgical intervention in patients with large tumor diameters or those at risk of rupture and bleeding. After rigorous preoperative evaluation and preparation, laparoscopic anatomical partial splenectomy is safe and feasible for surgeons with experience in laparoscopic surgery.

11.
Article in English | MEDLINE | ID: mdl-39302108

ABSTRACT

OBJECTIVE: The association between gastroesophageal reflux disease (GERD) and laryngeal disorders remains debatable, although it has been the focus of extensive clinical and laboratory research. We conducted this study to obtain evidence on the association. STUDY DESIGN: Population-based cohort study. SETTING: Taiwan National Health Insurance Research Database (NHIRD). METHODS: Using data from Taiwan's NHIRD (January 2000 to December 2018), we performed a population-based analysis to estimate the risk of laryngeal disorders in patients with GERD and those without GERD. RESULTS: The GERD and non-GERD cohorts comprised 176,319 and 705,276 patients, respectively. The cohorts were matched at a ratio of 1:4 based on sex, age, urbanization level, and income level. The risk of laryngeal disorders was higher in the GERD cohort than in the non-GERD cohort (adjusted hazard ratio: 1.64; 95% confidence interval: 1.61-1.67). CONCLUSION: This study is the first to use population data for identifying the association between GERD and laryngeal disorders for real-world findings. Our population-based analysis indicates that patients with GERD have an elevated risk of laryngeal disorders.

12.
Phytomedicine ; 134: 155993, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39244943

ABSTRACT

BACKGROUND: Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen., is widely used to treat cardiovascular and cerebrovascular diseases in China. Longxuetongluo Capsule (LTC) is a total phenolic compound extracted from Chinese dragon's blood, currently used in treating ischemic stroke. Myocardial injury can be aggravated after reperfusion of ischemic myocardium, which is called myocardial ischemia-reperfusion injury (MIRI), and the mechanism of MIRI is complex. However, the exact effect and mechanism of LTC on MIRI are still unclear. We explore the effect of LTC on alleviating MIRI based on mitochondrial dysfunction and oxidative stress. AIM OF THE STUDY: To explore the cardioprotective mechanism of LTC against MIRI. MATERIALS AND METHODS: A rat MIRI model was constructed through ligation of the left anterior descending coronary artery, and LTC was given continuously for 28 days before surgery. The H9c2 cardiomyocyte injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R), and LTC was given 24 h before OGD. Myocardial ischemia areas were detected with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cardiac histopathological changes were detected with hematoxylin-eosin (HE) staining. And biochemical indexes were detected with serum biochemical kit. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. Fluorescent probes were used to observe reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), Ca2+and other indexes. MitoTracker staining and immunofluorescence were used to observe the morphology of mitochondria and translocation of dynamin-related protein 1 (Drp1). Finally, immunohistochemistry and Western blotting were used to examine the expression of proteins related to apoptosis, mitochondrial fission and fusion and oxidative stress. RESULTS: LTC could ameliorate cardiac pathological changes, decrease myocardial infarct area and the content or level of relevant serum cardiac enzymes, indicating that LTC could alleviate MIRI. Meanwhile, LTC could inhibit cardiomyocyte apoptosis via regulating apoptosis-related protein expression, and it could restore mitochondrial morphology, maintain ΔΨm, inhibit mitochondrial ROS generation and Ca2+ accumulation, increase the expression of mitochondrial fusion protein 2 (Mfn2), decrease the level of phosphorylation dynamin-related protein 1 (p-Drp1), and regulate ATP synthesis, thereby significantly ameliorating mitochondrial dysfunction. Moreover, LTC significantly reduced the expression of NADPH oxidase 2 (NOX2), NADPH oxidase 4 (NOX4) and neutrophil cytosolic factor 2 (NOXA2/p67phox), and reduced ROS production. CONCLUSION: The study demonstrated that LTC could inhibit MIRI induced cardiomyocyte apoptosis by inhibiting ROS generation and mitochondrial dysfunction, and these fundings suggested that LTC can be used to alleviate MIRI, which provides a potential therapeutic approach for future treatment of MIRI.


Subject(s)
Apoptosis , Drugs, Chinese Herbal , Myocardial Reperfusion Injury , Myocytes, Cardiac , Oxidative Stress , Rats, Sprague-Dawley , Animals , Oxidative Stress/drug effects , Myocytes, Cardiac/drug effects , Apoptosis/drug effects , Myocardial Reperfusion Injury/drug therapy , Male , Rats , Drugs, Chinese Herbal/pharmacology , Reactive Oxygen Species/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Membrane Potential, Mitochondrial/drug effects , Cell Line , Dynamins/metabolism
13.
BMC Pulm Med ; 24(1): 445, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261802

ABSTRACT

BACKGROUND: Studies have found that in healthy individuals without nasal disease, changes in posture cause an increase in nasal resistance, especially in the prone posture. Many patients with obstructive sleep apnea syndrome (OSAS) sleep in a prone posture, but no studies have examined the effect of this change in posture on nasal resistance in patients with OSAS. Therefore, we conducted this study to investigate this posture-related physical phenomenon in individuals with OSAS. METHODS: We evaluated the nasal patency of 29 patients diagnosed with OSAS using the visual analog scale (VAS), acoustic rhinometry, and video-endoscopy in the sitting, supine, and prone postures. RESULTS: In the OSAS group, both supine and prone postures significantly influenced subjective nasal blockage and led to a notable reduction in the minimal cross-sectional area (mCSA) as determined by acoustic rhinometry, compared to the sitting posture. The prone posture exhibited a more pronounced effect than the supine posture. Endoscopic evaluations further revealed increased hypertrophy of the inferior turbinate in the supine posture for the right nasal passage and the prone posture for the left. However, no significant differences were observed between the prone and supine postures. CONCLUSION: In OSAS patients, nasal resistance significantly increased in supine and prone postures compared to sitting, with the prone posture showing a greater effect. Clinicians should consider a patient's habitual sleep posture and the effects of postural changes when assessing OSAS severity and devising treatment plans.


Subject(s)
Endoscopy , Rhinometry, Acoustic , Sleep Apnea, Obstructive , Humans , Sleep Apnea, Obstructive/physiopathology , Male , Middle Aged , Supine Position , Female , Adult , Prone Position , Sitting Position , Nasal Obstruction/physiopathology , Airway Resistance/physiology , Aged , Posture/physiology
14.
Microb Pathog ; 195: 106872, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39173852

ABSTRACT

Membrane lipoproteins serve as primary pro-inflammatory virulence factors in Mycoplasma genitalium. Membrane lipoproteins primarily induce inflammatory responses by activating Toll-like Receptor 2 (TLR2); however, the role of the metabolic status of urethral epithelial cells in inflammatory response remains unclear. In this study, we found that treatment of uroepithelial cell lines with M. genitalium membrane lipoprotein induced metabolic reprogramming, characterized by increased aerobic glycolysis, decreased oxidative phosphorylation, and increased production of the metabolic intermediates acetyl-CoA and malonyl-CoA. The metabolic shift induced by membrane lipoproteins is reversible upon blocking MyD88 and TRAM. Malonyl-CoA induces malonylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and malonylated GAPDH could dissociate from the 3' untranslated region of TNF-α and IFN-γ mRNA. This dissociation greatly reduces the inhibitory effect on the translation of TNF-α and IFN-γ mRNA, thus achieving fine-tuning control over cytokine secretion. These findings suggest that GAPDH malonylation following M. genitalium infection is an important inflammatory signal that plays a crucial role in urogenital inflammatory diseases.


Subject(s)
Cytokines , Epithelial Cells , Interferon-gamma , Mycoplasma genitalium , Tumor Necrosis Factor-alpha , Mycoplasma genitalium/metabolism , Mycoplasma genitalium/genetics , Epithelial Cells/metabolism , Epithelial Cells/microbiology , Humans , Cytokines/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interferon-gamma/metabolism , Cell Line , Lipoproteins/metabolism , Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism , Glyceraldehyde-3-Phosphate Dehydrogenases/genetics , Urethra/microbiology , Urethra/metabolism , Mycoplasma Infections/metabolism , Mycoplasma Infections/microbiology , Virulence Factors/metabolism , Myeloid Differentiation Factor 88/metabolism , Glycolysis , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 2/genetics
15.
Sci Data ; 11(1): 847, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103399

ABSTRACT

Mixed emotions have attracted increasing interest recently, but existing datasets rarely focus on mixed emotion recognition from multimodal signals, hindering the affective computing of mixed emotions. On this basis, we present a multimodal dataset with four kinds of signals recorded while watching mixed and non-mixed emotion videos. To ensure effective emotion induction, we first implemented a rule-based video filtering step to select the videos that could elicit stronger positive, negative, and mixed emotions. Then, an experiment with 80 participants was conducted, in which the data of EEG, GSR, PPG, and frontal face videos were recorded while they watched the selected video clips. We also recorded the subjective emotional rating on PANAS, VAD, and amusement-disgust dimensions. In total, the dataset consists of multimodal signal data and self-assessment data from 73 participants. We also present technical validations for emotion induction and mixed emotion classification from physiological signals and face videos. The average accuracy of the 3-class classification (i.e., positive, negative, and mixed) can reach 80.96% when using SVM and features from all modalities, which indicates the possibility of identifying mixed emotional states.


Subject(s)
Emotions , Humans , Electroencephalography , Facial Expression , Video Recording
16.
J Exp Clin Cancer Res ; 43(1): 218, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39103871

ABSTRACT

INTRODUCTION: Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a novel therapeutic strategy combining progesterone (Prog) and abiraterone (Abi) aimed at enhancing GBM treatment efficacy by modulating the tumor microenvironment and augmenting NK cell-mediated immunity. METHODS: We employed in vitro and in vivo GBM models to assess the effects of Prog and Abi on cell viability, proliferation, apoptosis, and the immune microenvironment. Techniques included cell viability assays, Glo-caspase 3/7 apoptosis assays, RNA-seq and qPCR for gene expression, Seahorse analysis for mitochondrial function, HPLC-MS for metabolomics analysis, and immune analysis by flow cytometry to quantify NK cell infiltration. RESULTS: Prog significantly reduced the IC50 of Abi in TMZ-resistant GBM cell, suggesting the enhanced cytotoxicity. Treatment induced greater apoptosis than either agent alone, suppressed tumor growth, and prolonged survival in mouse models. Notably, there was an increase in CD3-/CD19-/CD56+/NK1.1+ NK cell infiltration in treated tumors, indicating a shift towards an anti-tumor immune microenvironment. The combination therapy also resulted in a reduction of MGMT expression and a suppression of mitochondrial respiration and glycolysis in GBM cells. CONCLUSION: The combination of Prog and Abi represents a promising therapeutic approach for GBM, showing potential in suppressing tumor growth, extending survival, and modulating the immune microenvironment. These findings warrant further exploration into the clinical applicability of this strategy to improve outcomes for GBM patients.


Subject(s)
Glioblastoma , Killer Cells, Natural , Progesterone , Glioblastoma/drug therapy , Glioblastoma/pathology , Glioblastoma/metabolism , Glioblastoma/immunology , Humans , Mice , Animals , Killer Cells, Natural/immunology , Killer Cells, Natural/drug effects , Killer Cells, Natural/metabolism , Progesterone/pharmacology , Androstenes/pharmacology , Androstenes/therapeutic use , Cell Line, Tumor , Xenograft Model Antitumor Assays , Apoptosis/drug effects , Tumor Microenvironment/drug effects , Brain Neoplasms/drug therapy , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Disease Models, Animal
17.
ACS Appl Mater Interfaces ; 16(33): 43341-43349, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39103300

ABSTRACT

Cell-cell interactions play an important role in many biological processes, and various methods have been developed for controlling the cell-cell interactions. However, the effective and rapid control of intercellular interactions remains challenging. Herein, we report a novel, rapid, and effective electrochemical strategy without destroying the basic life processes for the dynamic control of intercellular interactions via liposome fusion. In the proposed system, bioorthogonal chemical groups and hydroquinone (HQ)- and aminooxy (AO)-tethered ligands were modified on the surface of living cells on the basis of the liposome fusion, enabling dynamical intercellular assemblies. Upon application of the corresponding oxidative potential, the "off-state" HQ could be oxidized to the "on-state" quinone (Q), which subsequently reacts with AO-tethered ligands to form stable oxime linkages under physiological conditions. This reaction effectively shortens the distance between cells, promoting the formation of cell clusters. When the corresponding reverse reductive potential is applied, the oxime linkage is cleaved, resulting in the release of the cells. Furthermore, we employed HQ- and AO-tethered ligands to modify mitochondria, inducing mitochondrial aggregation. This noninvasive and label-free strategy allows for the dynamic reversible regulation of intercellular interactions, enhancing our understanding of intercellular communication networks, and has the potential for improving the antitumor therapy efficacy.


Subject(s)
Cell Communication , Hydroquinones , Humans , Cell Communication/drug effects , Hydroquinones/chemistry , Hydroquinones/pharmacology , Liposomes/chemistry , Electrochemical Techniques , Mitochondria/metabolism , Mitochondria/drug effects , Ligands
18.
BMC Cancer ; 24(1): 965, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39107701

ABSTRACT

PURPOSE: This study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT). MATERIALS AND METHODS: This study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value < 0.05). These features were then employed to train and evaluate Logistic Regression (LR) and Random Forest (RF) models, using tenfold cross-validation to ensure robust assessment of model efficacy. RESULTS: In this study, 102 out of 120 VMAT-treated breast cancer patients were included in the detailed analysis. Thirty-two percent of these patients developed Grade 2+ RD. Age and BMI were identified as significant clinical predictors. Through feature selection, we narrowed down the vast pool of radiomic and dosiomic data to 689 features, distributed across 10 feature subsets for model construction. In the LR model, the J subset, comprising DVH, Radiomics, and Dosiomics features, demonstrated the highest predictive performance with an AUC of 0.82. The RF model showed that subset I, which includes clinical, radiomic, and dosiomic features, achieved the best predictive accuracy with an AUC of 0.83. These results emphasize that integrating radiomic and dosiomic features significantly enhances the prediction of Grade 2+ RD. CONCLUSION: Integrating clinical, radiomic, and dosiomic characteristics into AI models significantly improves the prediction of Grade 2+ RD risk in breast cancer patients post-VMAT. The RF model analysis demonstrates that a comprehensive feature set maximizes predictive efficacy, marking a promising step towards utilizing AI in radiation therapy risk assessment and enhancing patient care outcomes.


Subject(s)
Breast Neoplasms , Radiodermatitis , Radiotherapy, Intensity-Modulated , Humans , Breast Neoplasms/radiotherapy , Breast Neoplasms/diagnostic imaging , Female , Retrospective Studies , Middle Aged , Radiodermatitis/etiology , Radiodermatitis/diagnostic imaging , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Aged , Adult , Radiotherapy Planning, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Radiotherapy Dosage , Artificial Intelligence , Radiomics
19.
BMC Public Health ; 24(1): 2203, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138465

ABSTRACT

BACKGROUND: The newly described inflammatory burden index (IBI) reflects a patient's inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA. METHODS: We extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects. RESULTS: In total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices. CONCLUSIONS: This study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.


Subject(s)
Inflammation , Nutrition Surveys , Osteoarthritis , Humans , Male , Female , Osteoarthritis/mortality , Middle Aged , Aged , Inflammation/mortality , Adult , Cause of Death , Proportional Hazards Models , Risk Factors , United States/epidemiology
20.
Curr Issues Mol Biol ; 46(8): 7782-7794, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39194678

ABSTRACT

Astragalus polysaccharides (APSs), the compounds extracted from the common herb Astragalus membranaceus, have been extensively studied for their antitumor properties. In this study, we investigated the effect of APS on lung adenocarcinoma A549 cells. The effects of APS and the anti-diabetic drug metformin on apoptosis and ferroptosis were compared. Furthermore, the combination treatment of APS and metformin was also investigated. We found that APS not only reduced the growth of lung cancer cells but also had a synergistic effect with metformin on A549 cells. The study results showed that it may be promising to use APS and metformin as a combination therapy for the treatment of lung adenocarcinoma.

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