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1.
Front Neurol ; 15: 1407860, 2024.
Article in English | MEDLINE | ID: mdl-39091976

ABSTRACT

Amidst rising Parkinson's disease (PD) incidence in an aging global population, the need for non-invasive and reliable diagnostic methods is increasingly critical. This review evaluates the strategic role of transcranial sonography (TCS) in the early detection and monitoring of PD. TCS's ability to detect substantia nigra hyperechogenicity offers profound insights into its correlation with essential neuropathological alterations-namely, iron accumulation, neuromelanin depletion, and glial proliferation-fundamental to PD's pathophysiology. Our analysis highlights TCS's advantages, including its non-invasiveness, cost-effectiveness, and ease of use, positioning it as an invaluable tool for early diagnosis and continual disease progression monitoring. Moreover, TCS assists in identifying potential risk and protective factors, facilitating tailored therapeutic strategies to enhance clinical outcomes. This review advocates expanding TCS utilization and further research to maximize its diagnostic and prognostic potential in PD management, contributing to a more nuanced understanding of the disease.

2.
J Inflamm Res ; 17: 4345-4359, 2024.
Article in English | MEDLINE | ID: mdl-38979437

ABSTRACT

Purpose: The association between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) and cardiovascular risk in patients with coronary artery disease remains inconsistent. Recent investigations indicated potential dysfunctionality of HDL under inflammation. This study endeavors to explore whether the inflammatory status modifies the effects of HDL-C and ApoA-I on cardiovascular risk in individuals with percutaneous coronary intervention (PCI). Patients and Methods: Consecutive 10,724 PCI patients at Fuwai hospital in 2013 were enrolled. Inflammation status was defined by high-sensitivity C-reactive proteins (hsCRP) ≥ 2 mg/L. The study endpoint was cardiac mortality. Results: Among 9569 PCI patients eventually included, 225 (2.4%) cardiac mortality happened during 5 years. In hsCRP ≥ 2 mg/L group, an U-shaped curve was observed for HDL-C and multivariate Cox regression showed that elevated risks of cardiac mortality correlated to both the lowest quintile (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.32-4.71) and the highest quintile of HDL-C (HR, 2.28; 95% CI, 1.23-4.25). However, an L-shaped curve existed in ApoA-I, indicating only the lowest quintile level of ApoA-I was associated with an increased cardiac mortality risk (HR, 2.19; 95% CI, 1.28-3.75). Nevertheless, in hsCRP < 2 mg/L group, no significant correlations between HDL-C and ApoA-I and cardiac mortality risk were identified (both P > 0.05). Conclusion: In PCI patients with hsCRP ≥ 2 mg/L. both low and high HDL-C levels correlated with higher cardiac mortality risk (U-shaped), while only low ApoA-I levels were linked to elevated risk (L-shaped). However, in patients with hsCRP < 2 mg/L, neither HDL-C nor ApoA-I levels were associated with higher cardiac mortality risk. These findings shed light on the importance of considering inflammation status, particularly hsCRP levels, in managing HDL-C and ApoA-I levels, and suggest targeting elevated ApoA-I levels as a potential therapeutic approach for PCI patients with hsCRP ≥ 2 mg/L.

3.
Sensors (Basel) ; 24(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39065975

ABSTRACT

Air traffic controllers' mental workload significantly impacts their operational efficiency and safety. Detecting their mental workload rapidly and accurately is crucial for preventing aviation accidents. This study introduces a mental workload detection model for controllers based on power spectrum features related to gamma waves. The model selects the feature with the highest classification accuracy, ß + θ + α + γ, and utilizes the mRMR (Max-Relevance and Min-Redundancy) algorithm for channel selection. Furthermore, the channels that were less affected by ICA processing were identified, and the reliability of this result was demonstrated by artifact analysis brought about by EMG, ECG, etc. Finally, a model for rapid mental workload detection for controllers was developed and the detection rate for the 34 subjects reached 1, and the accuracy for the remaining subjects was as low as 0.986. In conclusion, we validated the usability of the mRMR algorithm in channel selection and proposed a rapid method for detecting mental workload in air traffic controllers using only three EEG channels. By reducing the number of EEG channels and shortening the data processing time, this approach simplifies equipment application and maintains detection accuracy, enhancing practical usability.


Subject(s)
Algorithms , Aviation , Electroencephalography , Workload , Humans , Electroencephalography/methods , Male , Adult , Signal Processing, Computer-Assisted , Female , Electrocardiography/methods
4.
bioRxiv ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38854114

ABSTRACT

The circadian clock orchestrates vital physiological processes such as metabolism, immune function, and tissue regeneration, aligning them with the optimal time of day. This study identifies an intricate interplay between the circadian clock within muscle stem cells (SCs) and their capacity to modulate the immune microenvironment during muscle regeneration. We uncover that the SC clock provokes time of day-dependent induction of inflammatory response genes following injury, particularly those related to neutrophil activity and chemotaxis. These responses are driven by rhythms of cytosolic regeneration of the signaling metabolite NAD+. We demonstrate that genetically enhancing cytosolic NAD+ regeneration in SCs is sufficient to induce robust inflammatory responses that significantly influence muscle regeneration. Furthermore, using mononuclear single-cell sequencing of the regenerating muscle niche, we uncover a key role for the cytokine CCL2 in mediating SC-neutrophil crosstalk in a time of day-dependent manner. Our findings highlight a crucial intersection between SC metabolic shifts and immune responses within the muscle microenvironment, dictated by the circadian rhythms, and underscore the potential for targeting circadian and metabolic pathways to enhance tissue regeneration.

5.
Arch Dermatol Res ; 316(7): 401, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878083

ABSTRACT

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.


Subject(s)
Glucosides , Hydrogen Peroxide , LIM Domain Proteins , Melanocytes , Monoterpenes , NF-E2-Related Factor 2 , Oxidative Stress , Signal Transduction , rho-Associated Kinases , rhoA GTP-Binding Protein , NF-E2-Related Factor 2/metabolism , rho-Associated Kinases/metabolism , Melanocytes/drug effects , Melanocytes/metabolism , Humans , Glucosides/pharmacology , Oxidative Stress/drug effects , rhoA GTP-Binding Protein/metabolism , Hydrogen Peroxide/metabolism , Signal Transduction/drug effects , LIM Domain Proteins/metabolism , LIM Domain Proteins/genetics , Monoterpenes/pharmacology , Cell Line
6.
Nat Commun ; 15(1): 5046, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871717

ABSTRACT

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.


Subject(s)
Niacinamide , Peripheral Arterial Disease , Pyridinium Compounds , Resveratrol , Humans , Peripheral Arterial Disease/drug therapy , Niacinamide/analogs & derivatives , Niacinamide/therapeutic use , Male , Female , Aged , Double-Blind Method , Resveratrol/therapeutic use , Resveratrol/pharmacology , Middle Aged , Walking , Treatment Outcome , Oxidative Stress/drug effects
7.
Exp Ther Med ; 28(2): 318, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38939177

ABSTRACT

The incidence of eye metastasis from primary malignant tumors is low. Predominantly, these primary malignant tumors consist of breast and lung carcinoma. Ocular metastatic carcinoma is often clinically overlooked. In clinical practice, it is rare for small-cell lung carcinoma (SCLC) to metastasize to the right eye. Early detection and treatment via the monitoring of clinical symptoms and auxiliary examinations of the eye are of great significance in preserving the patient's vision and improving their quality of life. Such treatments include radiotherapy or enucleation of the eyeball. A 54-year-old male patient with SCLC experienced a decline in vision and blurred vision during his systemic treatment using combined enverolumab and etoposide and cisplatin. Upon examination, including fundus photography, ocular B-scan and magnetic resonance imaging, a right eye metastasis was suspected. Within a short period of time, the patient experienced significant pain and blindness in the right eye, which required surgical removal of the right eyeball. Postoperative pathology confirmed metastasis. After six cycles of treatment, the primary lesion in the lung reduced in size. By reporting this case of SCLC metastasis to the right eye, we aim to provide a reference for the clinical diagnosis and treatment of ocular metastatic carcinoma.

8.
Technol Health Care ; 32(4): 2293-2306, 2024.
Article in English | MEDLINE | ID: mdl-38759031

ABSTRACT

BACKGROUND: Rehabilitation assessment is a critical component of rehabilitation treatment. OBJECTIVE: This study focuses on a comprehensive analysis of patients' movement performance using the upper limb rehabilitation robot. It quantitatively assessed patients' motor control ability and constructed an intelligent grading model of functional impairments. These findings contribute to a deeper understanding of patients' motor ability and provide valuable insights for personalized rehabilitation interventions. METHODS: Patients at different Brunnstrom stages underwent rehabilitation training using the upper limb rehabilitation robot, and data on the distal movement positions of the patients' upper limbs were collected. A total of 22 assessment metrics related to movement efficiency, smoothness, and accuracy were extracted. The performance of these assessment metrics was measured using the Mann-Whitney U test and Pearson correlation analysis. Due to the issue of imbalanced sample categories, data augmentation was performed using the Synthetic Minority Over-sampling Technique (SMOTE) algorithm based on weighted sampling, and an intelligent grading model of functional impairment based on the Extreme Gradient Boosting Tree (XGBoost) algorithm was constructed. RESULTS: Sixteen assessment metrics were screened. These metrics were effectively normalized to their maximum values, enabling the derivation of quantitative assessment scores for motor control ability across the three dimensions through a weighted fusion approach. Notably, when applied to the data-enhanced dataset, the intelligent grading model exhibited remarkable improvement, achieving an accuracy rate exceeding 0.98. Moreover, significant enhancements were observed in terms of precision, recall, and f1-score. CONCLUSION: The research findings demonstrate that this study enables the quantitative assessment of patients' motor control ability and intelligent grading of functional impairments, thereby contributing to the efficiency enhancement of clinical rehabilitation assessment. Moreover, this method resolves the issues associated with the subjectivity and prolonged periods of traditional rehabilitation assessment methods.


Subject(s)
Upper Extremity , Humans , Upper Extremity/physiopathology , Upper Extremity/physiology , Biomechanical Phenomena , Female , Male , Middle Aged , Adult , Robotics/methods , Algorithms , Aged , Movement/physiology
9.
Medicine (Baltimore) ; 103(19): e38106, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728498

ABSTRACT

RATIONALE: Recombinant human endostatin (Endostar) is extensively utilized in China for the clinical management of patients with driver gene-negative non-small cell lung cancer (NSCLC) at stage TNM IV. This report describes the case of a lung cancer patient treated exclusively with Endostar maintenance therapy, who experienced a rapid deterioration in respiratory function. PATIENT CONCERNS: The case involved a patient with a pathologically confirmed squamous cell carcinoma of the left lung, treated in our department. Following 1 month of albumin-bound paclitaxel chemotherapy and localized radiotherapy for the left lung lesion, the patient initiated treatment with a single agent, Endostar 30mg, on October 19, 2021. The medication was administered via intravenous infusion over a 7 days. DIAGNOSIS: On October 23, 2021, the patient exhibited symptoms of chest constriction, discomfort, coughing, and sputum production. By October 28, the patient presented with pronounced dyspnea and respiratory distress. An emergency CT scan detected pericardial tamponade and significant deviations in several blood parameters from pretreatment values. INTERVENTIONS: Percardial puncture and catheter drainage were recommended as therapeutic intervention. OUTCOMES: Considering the patient advanced age, the patient and their family opted to refuse this medical procedure, leading to the patient unfortunate demise on November 2, 2021. LESSONS: Medical professionals should remain vigilant for the potential, albeit rare, risk of Endostar inducing acute pericardial tamponade, a severe and potentially fatal complication.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Cardiac Tamponade , Endostatins , Lung Neoplasms , Recombinant Proteins , Humans , Carcinoma, Non-Small-Cell Lung/complications , Endostatins/therapeutic use , Lung Neoplasms/complications , Male , Cardiac Tamponade/etiology , Cardiac Tamponade/therapy , Recombinant Proteins/therapeutic use , Recombinant Proteins/administration & dosage , Fatal Outcome , Aged , Middle Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use
10.
Front Neurol ; 15: 1369492, 2024.
Article in English | MEDLINE | ID: mdl-38715688

ABSTRACT

Background: A novel inflammatory marker that measures the degree of systemic immunoinflammation, the systemic immuno-inflammation index (SII) is frequently used to forecast a number of illnesses. According to earlier studies, inflammation may play a role in the pathophysiology of hearing loss (HL). Methods: A sample from the National Health and Nutrition Examination Survey (NHANES) covering the years 2009 to 2018 was used in the current cross-sectional survey. Subgroup analysis and weighted multiple linear regression models were used to examine the independent linear correlation between SII and HL. Fitted smoothed curve analyses were also conducted to show the non-linear relationship between the two variables. Results: Among the 8,535 participants, the mean age was 40.92 ± 18.6 years, with 49.01% being male. Notably, individuals with hearing loss demonstrated an SII of 530.00 ± 320.72, while those with normal hearing displayed an SII of 491.21 ± 265.15. The mean ± SD values of low-frequency, speech-frequency, and high-frequency Pure Tone Average (PTA) hearing thresholds were 10.33 ± 9.79, 12.20 ± 11.11, and 22.48 ± 19.49 dB, respectively. A positive dose-response relationship between higher SII and hearing thresholds was observed after adjusting for potential confounders. Furthermore, the interaction analysis did not reveal any significant impact on this positive correlation. Conclusion: The results of our investigation suggest that the Systemic Inflammatory Index may serve as a potential biomarker for the likelihood of hearing loss. However, additional research is required to further elucidate the nature of this association.

11.
Curr Top Dev Biol ; 158: 307-339, 2024.
Article in English | MEDLINE | ID: mdl-38670711

ABSTRACT

Recent research has highlighted an important role for the molecular circadian machinery in the regulation of tissue-specific function and stress responses. Indeed, disruption of circadian function, which is pervasive in modern society, is linked to accelerated aging, obesity, and type 2 diabetes. Furthermore, evidence supporting the importance of the circadian clock within both the mature muscle tissue and satellite cells to regulate the maintenance of muscle mass and repair capacity in response injury has recently emerged. Here, we review the discovery of circadian clocks within the satellite cell (a.k.a. adult muscle stem cell) and how they act to regulate metabolism, epigenetics, and myogenesis during both healthy and diseased states.


Subject(s)
Circadian Rhythm , Regeneration , Satellite Cells, Skeletal Muscle , Satellite Cells, Skeletal Muscle/physiology , Satellite Cells, Skeletal Muscle/cytology , Satellite Cells, Skeletal Muscle/metabolism , Animals , Regeneration/physiology , Humans , Circadian Rhythm/physiology , Muscle, Skeletal/physiology , Muscle Development , Circadian Clocks/physiology , Epigenesis, Genetic
12.
Platelets ; 35(1): 2327835, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38655673

ABSTRACT

Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53-0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41-0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63-1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.


What is the context? Recent studies reported a paradoxical phenomenon that percutaneous coronary intervention (PCI) patients with thrombocytopenia (TP) were prone to experience thrombotic events. The potential mechanisms underlying the increased thrombotic risk and how to manage antiplatelet therapy in PCI patients with TP remain unclear.Growing attention has been paid to immunothrombosis. Inflammation is closely associated with high-on treatment platelet reactivity (HTPR) and thrombotic risk.HTPR is an independent risk factor of thrombosis and can provide information for guiding antiplatelet therapy.What is new? This prospective cohort study enrolled 10 724 patients undergoing PCI in Fuwai Hospital (National Center for Cardiovascular Diseases, Beijing, China), with HTPR risk being the study endpoint of interest.We first reported that inflammation significantly modified the platelet reactivity of PCI patients with TP.When hsCRP level <2 mg/L, PCI patients with TP had a decreased risk of HTPR. However, when hsCRP ≥2 mg/L, TP patients had similar HTPR risk as those without TP.HsCRP levels could modify the relationship between TP and HTPR risks both in patients with acute coronary syndrome and chronic coronary syndrome.What is the impact? These results provide insights into potential mechanisms of the increased thrombotic risk in PCI patients with TP. Specifically, inflammation might be involved in the thrombotic risk of PCI patients with TP by modifying the platelet reactivity.As for future management, personalized antiplatelet therapy should be administrated to TP patients with inflammation status.


Subject(s)
Percutaneous Coronary Intervention , Thrombocytopenia , Aged , Female , Male , Middle Aged , Blood Platelets , C-Reactive Protein/metabolism , China/epidemiology , Cohort Studies , Inflammation , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/statistics & numerical data , Prospective Studies , Thrombocytopenia/epidemiology , Thrombocytopenia/metabolism , Humans
14.
Commun Biol ; 7(1): 512, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684865

ABSTRACT

Neoantigens derived from somatic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), the most frequently mutated oncogene, represent promising targets for cancer immunotherapy. Recent research highlights the potential role of human leukocyte antigen (HLA) allele A*11:01 in presenting these altered KRAS variants to the immune system. In this study, we successfully generate and identify murine T-cell receptors (TCRs) that specifically recognize KRAS8-16G12V from three predicted high affinity peptides. By determining the structure of the tumor-specific 4TCR2 bound to KRASG12V-HLA-A*11:01, we conduct structure-based design to create and evaluate TCR variants with markedly enhanced affinity, up to 15.8-fold. This high-affinity TCR mutant, which involved only two amino acid substitutions, display minimal conformational alterations while maintaining a high degree of specificity for the KRASG12V peptide. Our research unveils the molecular mechanisms governing TCR recognition towards KRASG12V neoantigen and yields a range of affinity-enhanced TCR mutants with significant potential for immunotherapy strategies targeting tumors harboring the KRASG12V mutation.


Subject(s)
Antigens, Neoplasm , Proto-Oncogene Proteins p21(ras) , Receptors, Antigen, T-Cell , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/chemistry , Proto-Oncogene Proteins p21(ras)/immunology , Animals , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/metabolism , Antigens, Neoplasm/immunology , Antigens, Neoplasm/genetics , Antigens, Neoplasm/chemistry , Mice , Humans , Neoplasms/immunology , Neoplasms/genetics , Neoplasms/therapy , Mutation , Immunotherapy
15.
Lipids Health Dis ; 23(1): 100, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600516

ABSTRACT

BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.


Subject(s)
Lipid Accumulation Product , Sleep Apnea, Obstructive , Humans , Nutrition Surveys , Adiposity , Cross-Sectional Studies , Body Mass Index , Obesity, Abdominal/metabolism
16.
Heliyon ; 10(7): e27979, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38596066

ABSTRACT

Background: The clinically meaningful cardiac troponin I (cTnI) threshold associated with the long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective: To assess the association between different thresholds for post-procedural cTnI and 5-year mortality. Methods: The study included 4059 consecutive patients with normal baseline cTnI values who underwent elective PCI. The post-procedural cTnI level was measured at 8-48 h after PCI. The main study endpoints were 5-year all-cause mortality and cardiovascular mortality. Results: A cTnI ≥5 times the upper reference limit (URL) as defined by the fourth universal definition of myocardial infarction (4th UDMI), ≥35 times as defined by the Academic Research Consortium-2 criteria, and ≥70 times as defined by the Society for Cardiovascular Angiography and Interventions (SCAI [2014]) was identified in 33%, 6.6%, and 3.3% of patients, respectively. During 5 years of follow-up, the all-cause mortality rate was 3.4% (n = 132) and the cardiovascular mortality rate was 2.0% (n = 77). Both all-cause mortality and cardiovascular mortality increased with higher peak cTnI, and were independently predicted by a cTnI ≥70 times the URL (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.20-5.02 and adjusted HR 3.17, 95% CI 1.31-7.67, respectively; reference, cTnI <1 × URL]. The SCAI (2014) threshold was significantly associated with 5-year cardiovascular mortality (adjusted HR 2.66, 95% CI 1.20-5.89; reference, cTnI, <70 × URL) and all-cause mortality (adjusted HR 2.23, 95% CI 1.16-4.30; reference, cTnI <70 × URL). Conclusion: In patients with normal pre-procedural cTnI who underwent elective PCI, a post-procedural cTnI ≥70 times the URL independently predicted 5-year all-cause and cardiovascular mortality. Therefore, only the SCAI (2014) post-procedural cTnI threshold was independently associated with long-term mortality.

17.
Phytother Res ; 38(6): 2800-2817, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38526171

ABSTRACT

BACKGROUND AND AIM: Although the anti-cancer activity of isoalantolactone (IATL) has been extensively studied, the anti-melanoma effects of IATL are still unknown. Here, we have investigated the anti-melanoma effects and mechanism of action of IATL. MTT and crystal violet staining assays were performed to detect the inhibitory effect of IATL on melanoma cell viability. Apoptosis and cell cycle arrest induced by IATL were examined using flow cytometry. The molecular mechanism of IATL was explored by Western blotting, confocal microscope analysis, molecular docking, and cellular thermal shift assay (CETSA). A B16F10 allograft mouse model was constructed to determine the anti-melanoma effects of IATL in vivo. The results showed that IATL exerted anti-melanoma effects in vitro and in vivo. IATL induced cytoprotective autophagy in melanoma cells by inhibiting the PI3K/AKT/mTOR signaling. Moreover, IATL inhibited STAT3 activation both in melanoma cells and allograft tumors not only by binding to the SH2 domain of STAT3 but also by suppressing the activity of its upstream kinase Src. These findings demonstrate that IATL exerts anti-melanoma effects via inhibiting the STAT3 and PI3K/AKT/mTOR signaling pathways, and provides a pharmacological basis for developing IATL as a novel phytotherapeutic agent for treating melanoma clinically.


Subject(s)
Melanoma, Experimental , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , STAT3 Transcription Factor , Signal Transduction , TOR Serine-Threonine Kinases , Animals , STAT3 Transcription Factor/metabolism , TOR Serine-Threonine Kinases/metabolism , Mice , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Melanoma, Experimental/drug therapy , Melanoma, Experimental/metabolism , Apoptosis/drug effects , Mice, Inbred C57BL , Humans , Furans/pharmacology , Molecular Docking Simulation , Cell Survival/drug effects , Melanoma/drug therapy , Melanoma/metabolism , Autophagy/drug effects , Sesquiterpenes
18.
Huan Jing Ke Xue ; 45(3): 1859-1868, 2024 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-38471897

ABSTRACT

To investigate the influences of functional groups on the biological effects caused by microplastics, the accumulation of three polystyrene microplastics (PS, PS-NH2, and PS-COOH) in zebrafish (Danio rerio) embryos were analyzed, and then the responses of metabolic functions and microbial communities in zebrafish larvae were revealed using the combination of the microbiome and metabolome methods. The results showed that all microplastics could accumulate in zebrafish with concentrations ranging from 143 to 175 µg·g-1, and there were no significant differences in the accumulation potentials among different PS treatments. Exposure to plain PS significantly affected the metabolic capacity of aminoglycosides in zebrafish larvae, whereas the metabolic processes of amino acids were affected by PS-NH2. In the PS-COOH treatment, the metabolic pathways of the tricarboxylic acid cycle, amino acids, and glycolysis in zebrafish were markedly altered. The metabolic functions of zebrafish larvae were changed by all PS microplastics, resulting in toxic effects on zebrafish, and the functional group modification of microplastics may have further enhanced these toxicities. Compared to that in the control, exposure to PS-NH2 significantly reduced the diversity of microbial communities in zebrafish larvae and increased the proportion of Proteobacteria in the composition, leading to an imbalance of the bacterial community in zebrafish and thus disrupting the metabolic functions in the fish. Therefore, the functional modifications of microplastics may significantly alter the related stresses on aquatic organisms, leading to unpredictable ecological risks.


Subject(s)
Microplastics , Water Pollutants, Chemical , Animals , Zebrafish/metabolism , Plastics , Water Pollutants, Chemical/metabolism , Polystyrenes , Larva/metabolism , Amino Acids
19.
Langmuir ; 40(10): 5360-5368, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38427799

ABSTRACT

Emulsions, formed by dispersing a liquid into another immiscible one by virtue of emulsifiers, have been widely applied in commercial applications like foods, pharmaceuticals, cosmetics, and personal care, which always confront environmental and/or toxic questions due to emulsifiers' high dosage. Recently, a study on Pickering emulsions points out a solution to stable emulsions based on the costabilizing effect of colloidal particles, which focused on surface-active particles cooperating with oppositely charged ionic surfactants. Costabilized emulsions adopting a charge-similar ionic surfactant and particles were less studied. In this article, a hexane-in-water emulsion was prepared in use of a cationic surfactant cetyltrimethylammonium bromide (CTAB) with positively charged magnesium hydroxide (MH) nanosheets at low concentrations (10-5 M and 10-2 wt %, respectively). The emulsion is stable due to the synergy by CTAB and MH nanosheets, which functions in virtue of the electric repulsion by similarly charged particles, the mechanical shielding by MH nanosheets, and restrained water drainage in lamellae between droplets due to the gelation of MH nanosheets. Moreover, the emulsion is doubly switchable within emulsification/demulsification via convenient pH or ion manipulation, a mechanism based on the breakdown and rebuilding of the costabilizing synergy. Such dual-responsive emulsions show high potential for the delicate control of drug delivery, release, and biphasic biocatalysis applications.

20.
Liver Int ; 44(5): 1129-1141, 2024 May.
Article in English | MEDLINE | ID: mdl-38426611

ABSTRACT

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). METHODS: A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. RESULTS: The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). CONCLUSIONS: The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.


Subject(s)
Complement C3 , Non-alcoholic Fatty Liver Disease , Renal Insufficiency, Chronic , Humans , Complement C3/analysis , Liver Cirrhosis , Non-alcoholic Fatty Liver Disease/diagnosis , Renal Insufficiency, Chronic/diagnosis , Risk Factors , Asian People
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