Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS: Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.

A critical assessment of using ChatGPT for extracting structured data from clinical notes.

Existing natural language processing (NLP) methods to convert free-text clinical notes into structured data often require problem-specific annotations and model training. This study aims to evaluate ChatGPT's capacity to extract information from free-text medical notes efficiently and comprehensively. We developed a large language model (LLM)-based workflow, utilizing systems engineering methodology and spiral "prompt engineering" process, leveraging OpenAI's API for batch querying ChatGPT. We evaluated the effectiveness of this method using a dataset of more than 1000 lung cancer pathology reports and a dataset of 191 pediatric osteosarcoma pathology reports, comparing the ChatGPT-3.5 (gpt-3.5-turbo-16k) outputs with expert-curated structured data. ChatGPT-3.5 demonstrated the ability to extract pathological classifications with an overall accuracy of 89%, in lung cancer dataset, outperforming the performance of two traditional NLP methods. The performance is influenced by the design of the instructive prompt. Our case analysis shows that most misclassifications were due to the lack of highly specialized pathology terminology, and erroneous interpretation of TNM staging rules. Reproducibility shows the relatively stable performance of ChatGPT-3.5 over time. In pediatric osteosarcoma dataset, ChatGPT-3.5 accurately classified both grades and margin status with accuracy of 98.6% and 100% respectively. Our study shows the feasibility of using ChatGPT to process large volumes of clinical notes for structured information extraction without requiring extensive task-specific human annotation and model training. The results underscore the potential role of LLMs in transforming unstructured healthcare data into structured formats, thereby supporting research and aiding clinical decision-making.

Myricetin Acts as an Inhibitor of Type II NADH Dehydrogenase from Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. RESULTS: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 µM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 µg/mL. Time-kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. CONCLUSIONS: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.

Nitric oxide releasing nanofiber stimulates revascularization in response to ischemia via cGMP-dependent protein kinase.

Nitric oxide (NO) promotes angiogenesis via various mechanisms; however, the effective transmission of NO in ischemic diseases is unclear. Herein, we tested whether NO-releasing nanofibers modulate therapeutic angiogenesis in an animal hindlimb ischemia model. Male wild-type C57BL/6 mice with surgically-induced hindlimb ischemia were treated with NO-releasing 3-methylaminopropyltrimethoxysilane (MAP3)-derived or control (i.e., non-NO-releasing) nanofibers, by applying them to the wound for 20 min, three times every two days. The amount of NO from the nanofiber into tissues was assessed by NO fluorometric assay. The activity of cGMP-dependent protein kinase (PKG) was determined by western blot analysis. Perfusion ratios were measured 2, 4, and 14 days after inducing ischemia using laser doppler imaging. On day 4, Immunohistochemistry (IHC) with F4/80 and gelatin zymography were performed. IHC with CD31 was performed on day 14. To determine the angiogenic potential of NO-releasing nanofibers, aorta-ring explants were treated with MAP3 or control fiber for 20 min, and the sprout lengths were examined after 6 days. As per either LDPI (Laser doppler perfusion image) ratio or CD31 capillary density measurement, angiogenesis in the ischemic hindlimb was improved in the MAP3 nanofiber group; further, the total nitrate/nitrite concentration in the adduct muscle increased. The number of macrophage infiltrations and matrix metalloproteinase-9 (MMP-9) activity decreased. Vasodilator-stimulated phosphoprotein (VASP), one of the major substrates for PKG, increased phosphorylation in the MAP3 group. MAP3 nanofiber or NO donor SNAP (s-nitroso-n-acetyl penicillamine)-treated aortic explants showed enhanced sprouting in an ex vivo aortic ring assay, which was partially abrogated by KT5823, a potent inhibitor of PKG. These findings suggest that the novel NO-releasing nanofiber, MAP3 activates PKG and promotes therapeutic angiogenesis in response to hindlimb ischemia.

Cathepsin K deficiency prevented stress-related thrombosis in a mouse FeCl3 model.

BACKGROUND: Exposure to chronic psychological stress (CPS) is a risk factor for thrombotic cardiocerebrovascular diseases (CCVDs). The expression and activity of the cysteine cathepsin K (CTSK) are upregulated in stressed cardiovascular tissues, and we investigated whether CTSK is involved in chronic stress-related thrombosis, focusing on stress serum-induced endothelial apoptosis. METHODS AND RESULTS: Eight-week-old wild-type male mice (CTSK+/+) randomly divided to non-stress and 3-week restraint stress groups received a left carotid artery iron chloride3 (FeCl3)-induced thrombosis injury for biological and morphological evaluations at specific timepoints. On day 21 post-stress/injury, the stress had enhanced the arterial thrombi weights and lengths, in addition to harmful alterations of plasma ADAMTS13, von Willebrand factor, and plasminogen activation inhibitor-1, plus injured-artery endothelial loss and CTSK protein/mRNA expression. The stressed CTSK+/+ mice had increased levels of injured arterial cleaved Notch1, Hes1, cleaved caspase8, matrix metalloproteinase-9/-2, angiotensin type 1 receptor, galactin3, p16IN4A, p22phox, gp91phox, intracellular adhesion molecule-1, TNF-α, MCP-1, and TLR-4 proteins and/or genes. Pharmacological and genetic inhibitions of CTSK ameliorated the stress-induced thrombus formation and the observed molecular and morphological changes. In cultured HUVECs, CTSK overexpression and silencing respectively increased and mitigated stressed-serum- and H2O2-induced apoptosis associated with apoptosis-related protein changes. Recombinant human CTSK degraded γ-secretase substrate in a dose-dependent manor and activated Notch1 and Hes1 expression upregulation. CONCLUSIONS: CTSK appeared to contribute to stress-related thrombosis in mice subjected to FeCl3 stress, possibly via the modulation of vascular inflammation, oxidative production and apoptosis, suggesting that CTSK could be an effective therapeutic target for CPS-related thrombotic events in patients with CCVDs.

Dipeptidyl peptidase-4 disturbs adipocyte differentiation via the negative regulation of the glucagon-like peptide-1/adiponectin-cathepsin K axis in mice under chronic stress conditions.

Exposure to chronic psychosocial stress is a risk factor for metabolic disorders. Because dipeptidyl peptidase-4 (DPP4) and cysteinyl cathepsin K (CTSK) play important roles in human pathobiology, we investigated the role(s) of DPP4 in stress-related adipocyte differentiation, with a focus on the glucagon-like peptide-1 (GLP-1)/adiponectin-CTSK axis in vivo and in vitro. Plasma and inguinal adipose tissue from non-stress wild-type (DPP4+/+), DPP4-knockout (DPP4-/-) and CTSK-knockout (CTSK-/-) mice, and stressed DPP4+/+, DPP4-/-, CTSK-/-, and DPP4+/+ mice underwent stress exposure plus GLP-1 receptor agonist exenatide loading for 2 weeks and then were analyzed for stress-related biological and/or morphological alterations. On day 14 under chronic stress, stress decreased the weights of adipose tissue and resulted in harmful changes in the plasma levels of DPP4, GLP-1, CTSK, adiponectin, and tumor necrosis factor-α proteins and the adipose tissue levels of CTSK, preadipocyte factor-1, fatty acid binding protein-4, CCAAT/enhancer binding protein-α, GLP-1 receptor, peroxisome proliferator-activated receptor-γ, perilipin2, secreted frizzled-related protein-4, Wnt5α, Wnt11 and ß-catenin proteins and/or mRNAs as well as macrophage infiltration in adipose tissue; these changes were rectified by DPP4 deletion. GLP-1 receptor activation and CTSK deletion mimic the adipose benefits of DPP4 deficiency. In vitro, CTSK silencing and overexpression respectively prevented and facilitated stress serum and oxidative stress-induced adipocyte differentiation accompanied with changes in the levels of pref-1, C/EBP-α, and PPAR-γ in 3T3-L1 cells. Thus, these findings indicated that increased DPP4 plays an essential role in stress-related adipocyte differentiation, possibly through a negative regulation of GLP-1/adiponectin-CTSK axis activation in mice under chronic stress conditions.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Vaccinating with Valor: A Risk Preventive Model to Explain Factors in Parents' Choice to Vaccinate Their Children for COVID-19.

Childhood immunization can effectively control and prevent infectious diseases; however, not all parents choose to vaccinate their children against vaccines, including COVID-19. This study aimed to determine potential factors influencing people's willingness to vaccinate their children. An online survey was conducted with 509 adult parents/guardians of children to test our hypotheses. Based on the TPB model with the RISP model as the antecedent, results indicated that people's systematic risk information processing, trust in science, and concerns about the disease positively influenced their cognitive structure, further impacting their attitude toward vaccinating their children. The results also verified that attitude toward vaccination and perceived behavioral control are both significant predictors of parents/guardians' intention to vaccinate their children. The results contribute to health risk communicators creating effective strategies to better communicate with adults and increase intentions to vaccinate their children.

Enhancing the Flame Retardancy of Polyester/Cotton Blend Fabrics Using Biobased Urea-Phytate Salt.

The use of biobased flame-retardant (FR) agents for reducing the flammability of polyester/cotton (T/C) blend fabrics is highly desirable. In this study, a novel and sustainable phosphorus/nitrogen-containing FR, namely, phytic acid-urea (PA-UR) salt, was synthesized. The PA-UR salt was further used to enhance the FR performance of T/C fabric through surface modification. We further explored the potential chemical structure of PA-UR and the surface morphology, thermal stability, heat release capacity, FR properties, and mode of action of the coated fabric. The coated fabric achieved self-extinguishing and exhibited an increased limiting oxygen index of 31.8%. Moreover, the coated T/C blend fabric demonstrated a significantly reduced heat release capacity, indicating a decreased fire hazard. Thermogravimetric analysis revealed the anticipated decomposition of the coated T/C blend fabric and a subsequent increase in thermal stability. The burned char residues also maintained their fiber shape structures, suggesting the presence of condensed FR actions in the PA-UR-coated T/C blend fabric.

Comparative Analysis of Agronomic Traits, Yield, and Effective Components of Main Cultivated Ganoderma Mushrooms (Agaricomycetes) in China.

To assess the strain resources and address production challenges in Ganoderma cultivation. 150 Ganoderma strains were collected from 13 provinces in China. A comparative analysis of agronomic traits and effective components was conducted. Among the 150 strains, key agronomic traits measured were: average stipe diameter (15.92 mm), average stipe length (37.46 mm), average cap horizontal diameter (94.97 mm), average cap vertical diameter (64.21 mm), average cap thickness (15.22 mm), and average fruiting body weight (14.30 g). Based on these agronomic traits, four promising strains, namely, L08, L12, Z21, and Z39, were recommended for further cultivation and breeding. The average crude polysaccharide content ranged from 0.048% to 0.977%, and triterpenoids ranged from 0.804% to 2.010%. In addition, 73 triterpenoid compounds were identified, constituting 47.1% of the total compounds. Using a distance discrimination method, the types, and relative contents of triterpenoid compounds in 150 Ganoderma strains were classified, achieving 98% accuracy in G. lingzhi identification. The 16 triterpenoid components used for G. lingzhi identification included oleanolic acid, ursolic acid, 3ß-acetoxyergosta-7,22-dien-5α-ol, ganoderic acid DM, ganoderiol B, ganorderol A, ganoderic acid GS-1, tsugaric acid A, ganoderic acid GS-2, ganoderenic acid D, ganoderic acid Mf, ganoderic acid A, ganoderic acid K, ganoderic acid V, ganoderic acid G, and leucocontextin J. This study provides valuable insights for exploring and utilizing Ganoderma resources and for the development of new varieties.

A Case of Hepatotoxicity Induced by Therapeutic Ketamine Use for Sedation.

Ketamine, initially developed as an anesthetic, has shown versatility in medical applications, including pain management, treatment-resistant depression, and sedation in the intensive care unit (ICU). While generally well-tolerated, long-term use at high doses raises concerns about potential toxicities, particularly in the liver. We present a case of a 27-year-old female with a complex medical history who received ketamine infusion for ICU sedation and experienced a sudden rise in liver function tests (LFTs), indicating possible ketamine-induced liver injury (KILI). The patient's liver function normalized after ketamine discontinuation. KILI is infrequent with short-term ketamine use, but emerging case reports suggest it may be associated with chronic or intermittent exposure. The underlying mechanisms for KILI are not fully understood but may involve the accumulation of ketamine metabolites, causing direct toxic effects on the liver. As ketamine's use expands, especially in critical care settings, clinicians should be vigilant for the potential development of KILI. Further research is needed to better understand its risk factors and mechanisms, as early detection and management of KILI are crucial to ensuring patient safety and optimizing ketamine's therapeutic benefits.

Preoperative Serum Thyroglobulin Levels Predict Radioiodine Therapy Outcome in Papillary Thyroid Microcarcinoma Patients.

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT.

Population genetics provides insights into the important agronomic traits of Ganoderma cultivation varieties in China.

This study aimed to investigate the species diversity and genetic differentiation of the genome of the main cultivated strains of Ganoderma in China. Population genomics analysis was conducted based on 150 cultivated strains of Ganoderma collected nationwide. The results indicated that the main species currently cultivated in China were Ganoderma sichuanense and Ganoderma lucidum, with a minor proportion of Ganoderma sessile, Ganoderma weberianum, Ganoderma sinense, Ganoderma gibbosum and Ganoderma australe. A total of 336,506 high-quality single nucleotide polymorphism (SNP) loci were obtained through population evolution analysis. The Fst values were calculated using a 5-kb sliding window, which ranged from 0.11 to 0.74. This suggests varying degrees of genetic differentiation between populations and genetic exchange among varieties. On this basis, the genes related to the stipe length, cap color and branch phenotypes of Ganoderma were excavated, and the region with the top 1% ZFst value region was used as a candidate region. A total of 137, 270 and 222 candidate genes were identified in the aforementioned 3 phenotypes, respectively. Gene annotation revealed that genes associated with stipe length were mainly related to cell division and differentiation, including proteins such as Nse4 protein and DIM1 protein. The genes related to Ganoderma red color were mainly related to the metabolism of tryptophan and flavonoids. The genes related to the branch were mainly related to cytokinin synthesis, ABC transporter and cytochrome P450. This study provided 150 valuable genome resequencing data in assessing the diversity and genetic differentiation of Ganoderma and laid a foundation for agronomic trait analysis and the development of new varieties of Ganoderma.

Preparation of MoS2@PDA-Modified Polyimide Films with High Mechanical Performance and Improved Electrical Insulation.

Polyimide (PI) has been widely used in cable insulation, thermal insulation, wind power protection, and other fields due to its high chemical stability and excellent electrical insulation and mechanical properties. In this research, a modified PI composite film (MoS2@PDA/PI) was obtained by using polydopamine (PDA)-coated molybdenum disulfide (MoS2) as a filler. The low interlayer friction characteristics and high elastic modulus of MoS2 provide a theoretical basis for enhancing the flexible mechanical properties of the PI matrix. The formation of a cross-linking structure between a large number of active sites on the surface of the PDA and the PI molecular chain can effectively enhance the breakdown field strength of the film. Consequently, the tensile strength of the final sample MoS2@PDA/PI film increased by 44.7% in comparison with pure PI film, and the breakdown voltage strength reached 1.23 times that of the original film. It can be seen that the strategy of utilizing two-dimensional (2D) MoS2@PDA nanosheets filled with PI provides a new modification idea to enhance the mechanical and electrical insulation properties of PI films.

Gray Matter Abnormalities in Patients with Chronic Low Back Pain: A Systematic Review and Meta-Analysis of Voxel-Based Morphometry Studies.

BACKGROUND: Numerous studies utilizing voxel-based morphometry (VBM) have documented gray matter (GM) alterations in patients with chronic low back pain (CLBP) compared to healthy controls. However, the inconsistency in GM abnormalities observed across different studies has hindered their potential application as objective neuroimaging biomarkers or therapeutic targets. To address this issue, we conducted a comprehensive meta-analysis of VBM studies to identify robust GM differences between CLBP patients and healthy controls. METHODS: The databases including PubMed, Embase, and Web of Science were systematically searched from January 2000 to September 2022 to identify eligible neuroimaging studies. In this coordinate-based meta-analysis of VBM studies, the Seed-based d Mapping with Permutation of Subject Images method was used to quantitatively assess regional differences in GM between CLBP patients and healthy controls. RESULTS: Thirteen VBM studies, involving a total of 574 CLBP patients and 1239 healthy controls, were included in the meta-analysis. The findings revealed that CLBP patients exhibited increased GM in the left striatum and left postcentral gyrus and decreased GM in the left superior frontal gyrus, left cerebellum, right striatum, left insula, and right middle occipital gyrus compared to healthy controls. The jackknife sensitivity analysis confirmed the robustness of these neuroimaging findings. CONCLUSIONS: This study provides new insights into potential treatment strategies for CLBP and identifies neuroimaging biomarkers for pain chronification. These findings highlight the importance of considering regional GM abnormalities in the development of clinical interventions for CLBP.

The many roles of cathepsins in restenosis.

Drug-eluting stents (DES) and dual antiplatelet regimens have significantly improved the clinical management of ischemic heart disease; however, the drugs loaded with DES in clinical practice are mostly paclitaxel or rapamycin derivatives, which target symptoms of post implantation proliferation and inflammation, leading to delayed re-endothelialization and neo-atherosclerosis. Along with the treatments already in place, there is a need for novel strategies to lessen the negative clinical outcomes of DES delays as well as a need for greater understanding of their pathobiological mechanisms. This review concentrates on the function of cathepsins (Cats) in the inflammatory response and granulation tissue formation that follow Cat-induced damage to the vasculature scaffold, as well as the functions of Cats in intimal hyperplasia, which is characterized by the migration and proliferation of smooth muscle cells, and endothelial denudation, re-endothelialization, and/or neo-endothelialization. Additionally, Cats can alter essential neointima formation and immune response inside scaffolds, and if Cats are properly controlled in vivo, they may improve scaffold biocompatibility. This unique profile of functions could lead to an original concept for a cathepsin-based coronary intervention treatment as an adjunct to stent placement.

Recurrent syncope driven by unique-variant angina pectoris.

The patient's vasospastic variant angina manifested as syncope with asymptomatic ischemic episodes, and repeated 24-h dynamic electrocardiogram and coronary angiography examinations combined with coronary provocation spasm tests were necessary for its diagnosis and management.

Aucubin protects against myocardial ischemia-reperfusion injury by regulating STAT3/NF-κB/HMGB-1 pathway.

The main characteristics of the myocardial ischemia/reperfusion injury (MI/RI) are oxidative stress, apoptosis, and an inflammatory response. Aucubin (AU) is an iridoid glycoside that possesses various biological properties and has been discovered to demonstrate antioxidant and anti-inflammatory impacts in pathological processes, such as ischemia-reperfusion. The objective of this research was to investigate if AU treatment could mitigate myocardial inflammation and apoptosis caused by ischemia/reperfusion (I/R) in both laboratory and animal models, and to elucidate its underlying mechanism. By ligating the coronary artery on the left anterior descending side, a successful MI/RI rat model was created. Additionally, H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in order to imitate the injury caused by ischemia/reperfusion (I/R). Furthermore, various concentrations of AU were administered to H9C2 cells or rats before H/R stimulation or myocardial I/R surgery, respectively. In vitro, the assessment was conducted on cardiac function, inflammatory markers, and myocardial pathology. In vivo, we examined the viability of cells, as well as factors related to apoptosis and oxidative stress. Furthermore, the presence of proteins belonging to the STAT3/NF-κB/HMGB1 signaling pathway was observed both in vivo and in vitro. AU effectively improved cardiomyocyte injury caused by H/R and myocardial injury caused by I/R. Furthermore, AU suppressed the production of reactive oxygen species and inflammatory molecules (TNF-alpha, IL-1ß, and IL-6) and proteins associated with cell death (caspase-3 and Bax), while enhancing the levels of anti-inflammatory agents (IL-10) and the anti-apoptotic protein Bcl-2.AU mechanistically affected the phosphorylation of STAT3 at the Ser727 site and Tyr705 following H/R by modulating the signaling pathway involving signal transducer and activator of transcription 3 (STAT3)/nuclear factor-κB (NF-κB)/high mobility group box 1 (HMGB1), while also suppressing the nuclear translocation of NF-κB p65 and HMGB1 exonucleation. In conclusion, the use of AU treatment might offer protection against myocardial infarction and injury by reducing oxidative stress, suppressing apoptosis, and mitigating inflammation. The regulation of the STAT3/NF-κB/HMGB-1 pathway may contribute to this phenomenon by affecting STAT3 phosphorylation and controlling NF-κB and HMGB-1 translocation. Contributes to identifying possible objectives for myocardial ischemia/reperfusion damage.

Multi-Omics Characteristics of Ferroptosis Associated with Colon Adenocarcinoma Typing and Survival.

BACKGROUND: Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of various cancers, including colon adenocarcinoma (COAD). However, the multi-omics signatures relevant to ferroptosis regulation in COAD diagnosis remain to be elucidated. METHODS: The transcriptomic, miRNAomic, and methylomic profiles of COAD patients were acquired from the Cancer Genome Atlas (TCGA). Ferroptosis activity in these patients was determined, represented by a ferroptosis score (FS), using single-sample gene set enrichment analysis (ssGSEA) based on the expression of ferroptosis-related genes. RESULTS: Results showed that the COAD patients with high-FS displayed favorable survival outcomes and heightened drug sensitivity. They also exhibited an up-regulation of genes involved in immune-related pathways (e.g., tumor necrosis factor signaling pathway), suggesting a correlation between immunity and ferroptosis in COAD progression. Furthermore, three survival prediction models were established based on 10 CpGs, 12 long non-coding RNAs (lncRNAs), and 14 microRNAs (miRNAs), respectively. These models demonstrated high accuracy in predicting COAD survival, achieving areas under the curve (AUC) >0.7. The variables used in the three models also showed strong correlations at different omics levels and were effective at discriminating between high-FS and low-FS COAD patients (AUC >0.7). CONCLUSIONS: This study identified different DNA methylation (DNAm), lncRNA, and miRNA characteristics between COAD patients with high and low ferroptosis activity. Furthermore, ferroptosis-related multi-omics signatures were established for COAD prognosis and classification. These insights present new opportunities for improving the efficacy of COAD therapy.