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1.
Heliyon ; 10(13): e33738, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39050439

RESUMEN

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.

2.
FASEB J ; 38(13): e23786, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38979903

RESUMEN

Regulatory T cells (Tregs) are crucial in regulating T-cell-mediated immune responses. Numerous studies have shown that dysfunction or decreased numbers of Tregs may be involved in inflammatory cardiovascular diseases (CVDs) such as atherosclerosis, hypertension, myocardial infarction, myocarditis, cardiomyopathy, valvular heart diseases, heart failure, and abdominal aortic aneurysm. Tregs can help to ameliorate CVDs by suppressing excessive inflammation through various mechanisms, including inhibition of T cells and B cells, inhibition of macrophage-induced inflammation, inhibition of dendritic cells and foam cell formation, and induction of anti-inflammatory macrophages. Enhancing or restoring the immunosuppressive activity of Tregs may thus serve as a fundamental immunotherapy to treat hypertension and CVDs. However, the precise molecular mechanisms underlying the Tregs-induced protection against hypertension and CVDs remain to be investigated. This review focuses on recent advances in our understanding of Tregs subsets and function in CVDs. In addition, we discuss promising strategies for using Tregs through various pharmacological approaches to treat hypertension and CVDs.


Asunto(s)
Enfermedades Cardiovasculares , Linfocitos T Reguladores , Humanos , Linfocitos T Reguladores/inmunología , Enfermedades Cardiovasculares/inmunología , Animales , Inflamación/inmunología
3.
Phytochem Anal ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39072803

RESUMEN

INTRODUCTION: The identification of Aucklandiae Radix (AR), Vladimiriae Radix (VR), and Inulae Radix (IR) based on traits and microscopic features is susceptible to the state of samples and the subjective awareness of personnel, and the identification based on a few or single chemical compositions is a cumbersome and time-consuming procedure and fails to rationally and effectively utilize the information of unknown components and is not specificity enough. OBJECTIVES: This study aimed to improve the identification efficiency, strengthen supervision, and realize digital identification of three Chinese medicines. Ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) combined with multivariate algorithms was used to explore the digital identification of AR, VR, and IR. MATERIALS AND METHODS: UHPLC-QTOF-MS was used to analyze AR, VR, and IR. The MS data combined with multivariate algorithms such as partial least squares discrimination analysis (PLS-DA) and artificial neural networks (ANNs) was used to filter important variables and data modeling. Finally, the optimal model was selected for the digital identification of three herbs. RESULTS: The results showed that three herbs can be distinguished on the whole level, and through feature screening, 591 characteristic variables combined with multivariate algorithms to construct data models. The ANN model was the best with accuracy = 0.983, precision = 0.984, and external verification showed the reliability and practicability of ANN model. CONCLUSION: ANN model combined with MS data is of great significance for tdigital identification of AR, VR, and IR. It is an important reference for developing the digital identification of traditional Chinese medicines at the individual level based on UHPLC-QTOF-MS and multivariate algorithms.

4.
Front Public Health ; 12: 1410713, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939559

RESUMEN

Introduction: Ticks and pathogens they carry seriously impact human and animal health, with some diseases like Lyme and Alpha-gal syndrome posing risks. Searching for health information online can change people's health and preventive behaviors, allowing them to face the tick risks. This study aimed to predict the potential risks of tickborne diseases by examining individuals' online search behavior. Methods: By scrutinizing the search trends across various geographical areas and timeframes within the United States, we determined outdoor activities associated with potential risks of tick-related diseases. Google Trends was used as the data collection and analysis tool due to its accessibility to big data on people's online searching behaviors. We interact with vast amounts of population search data and provide inferences between population behavior and health-related phenomena. Data were collected in the United States from April 2022 to March 2023, with some terms about outdoor activities and tick risks. Results and Discussion: Results highlighted the public's risk susceptibility and severity when participating in activities. Our results found that searches for terms related to tick risk were associated with the five-year average Lyme Disease incidence rates by state, reflecting the predictability of online health searching for tickborne disease risks. Geographically, the results revealed that the states with the highest relative search volumes for tick-related terms were predominantly located in the Eastern region. Periodically, terms can be found to have higher search records during summer. In addition, the results showed that terms related to outdoor activities, such as "corn maze," "hunting," "u-pick," and "park," have moderate associations with tick-related terms. This study provided recommendations for effective communication strategies to encourage the public's adoption of health-promoting behaviors. Displaying warnings in the online search results of individuals who are at high risk for tick exposure or collaborating with outdoor activity locations to disseminate physical preventive messages may help mitigate the risks associated with tickborne diseases.


Asunto(s)
Motor de Búsqueda , Enfermedades por Picaduras de Garrapatas , Humanos , Enfermedades por Picaduras de Garrapatas/prevención & control , Enfermedades por Picaduras de Garrapatas/epidemiología , Estados Unidos , Animales , Motor de Búsqueda/estadística & datos numéricos , Internet , Enfermedad de Lyme/prevención & control , Enfermedad de Lyme/epidemiología , Garrapatas , Conducta en la Búsqueda de Información
5.
Int J Surg ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874473

RESUMEN

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

6.
Chin J Integr Med ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38850483

RESUMEN

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.

7.
Int J Biol Macromol ; 273(Pt 2): 133129, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38885864

RESUMEN

For protein fibers, polycarboxylic acids represent a green strategy to enhance durability without using formaldehyde. This study evaluated the physical and flame retardant properties of silk fabrics treated with three formaldehyde-free crosslinkers: citric acid (CA), 1,2,3,4-butanetetracarboxylic acid (BTCA), and 2-phosphonobutane-1,2,4-tricarboxylic acid (PBTCA). Results showed that these acids bond with silk protein through esterification and amidation, improving washing durability. Particularly, PBTCA integrates phosphorus into silk, boosting flame retardancy. While BTCA led to the highest weight gain and improved wrinkle recovery, it negatively impacted the tensile strength and softness of silk fabrics. Conversely, PBTCA adeptly balanced enhanced wrinkle resistance with minimal effects on tensile strength and softness, and least affected the silk fabrics' whiteness, thus preserving its aesthetic appeal. All crosslinkers improved flame retardancy, but PBTCA displayed superior performance, achieving a limiting oxygen index of 32.4 % at an 80 g/L concentration. In vertical burning tests, PBTCA treated silk fabrics showed reductions in damage length and demonstrated self-extinguishing properties, qualifying them for a higher flame retardant grade. Phosphorus in PBTCA promotes char formation during combustion, essential for effective flame retardation and smoke reduction. This research highlights the exceptional potential of silk treated with PBTCA, showcasing its suitability for demanding applications.


Asunto(s)
Retardadores de Llama , Seda , Resistencia a la Tracción , Textiles , Seda/química , Ácidos Carboxílicos/química , Reactivos de Enlaces Cruzados/química
8.
PLoS One ; 19(5): e0303758, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38768136

RESUMEN

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.


Asunto(s)
Proteínas Quinasas Dependientes de GMP Cíclico , Miembro Posterior , Isquemia , Ratones Endogámicos C57BL , Nanofibras , Neovascularización Fisiológica , Óxido Nítrico , Animales , Nanofibras/química , Masculino , Óxido Nítrico/metabolismo , Isquemia/tratamiento farmacológico , Isquemia/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Ratones , Miembro Posterior/irrigación sanguínea , Neovascularización Fisiológica/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Fosfoproteínas/metabolismo , Proteínas de Microfilamentos/metabolismo , Moléculas de Adhesión Celular
9.
Molecules ; 29(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38792214

RESUMEN

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.


Asunto(s)
Flavonoides , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Flavonoides/farmacología , Flavonoides/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/enzimología , Antibacterianos/farmacología , Antibacterianos/química , NADH Deshidrogenasa/antagonistas & inhibidores , NADH Deshidrogenasa/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Animales , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Humanos , Factores de Virulencia/antagonistas & inhibidores , Factores de Virulencia/metabolismo
11.
FASEB J ; 38(10): e23684, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38795334

RESUMEN

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.


Asunto(s)
Adipocitos , Adiponectina , Catepsina K , Diferenciación Celular , Dipeptidil Peptidasa 4 , Péptido 1 Similar al Glucagón , Ratones Noqueados , Animales , Ratones , Adiponectina/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Adipocitos/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Dipeptidil Peptidasa 4/genética , Catepsina K/metabolismo , Catepsina K/genética , Masculino , Ratones Endogámicos C57BL , Estrés Psicológico/metabolismo , Células 3T3-L1 , Exenatida/farmacología , PPAR gamma/metabolismo , Adipogénesis
12.
Oral Oncol ; 153: 106834, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38718458

RESUMEN

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.


Asunto(s)
Árboles de Decisión , Carcinoma Nasofaríngeo , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/terapia , Estudios Retrospectivos , Adulto , Estadificación de Neoplasias , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Pronóstico , Anciano
13.
Cell Mol Life Sci ; 81(1): 205, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38703204

RESUMEN

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.


Asunto(s)
Apoptosis , Catepsina K , Cloruros , Modelos Animales de Enfermedad , Compuestos Férricos , Trombosis , Animales , Humanos , Masculino , Ratones , Proteína ADAMTS13/metabolismo , Proteína ADAMTS13/genética , Catepsina K/metabolismo , Catepsina K/genética , Cloruros/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Trombosis/metabolismo , Trombosis/patología , Factor de Transcripción HES-1/metabolismo , Factor de Transcripción HES-1/genética
14.
NPJ Digit Med ; 7(1): 106, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693429

RESUMEN

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.

15.
Health Commun ; : 1-11, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591234

RESUMEN

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.

16.
Horm Metab Res ; 56(7): 498-503, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38503312

RESUMEN

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.


Asunto(s)
Carcinoma Papilar , Radioisótopos de Yodo , Tiroglobulina , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Radioisótopos de Yodo/uso terapéutico , Femenino , Tiroglobulina/sangre , Masculino , Persona de Mediana Edad , Adulto , Carcinoma Papilar/radioterapia , Carcinoma Papilar/sangre , Carcinoma Papilar/patología , Pronóstico , Resultado del Tratamiento , Periodo Preoperatorio , Anciano , Biomarcadores de Tumor/sangre , Estudios Retrospectivos
17.
Case Rep Crit Care ; 2024: 8366034, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505599

RESUMEN

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.

18.
Materials (Basel) ; 17(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38541499

RESUMEN

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.

19.
Int J Med Mushrooms ; 26(4): 9-27, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38523446

RESUMEN

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.


Asunto(s)
Agaricales , Agaricus , Antineoplásicos , Ganoderma , Reishi , Triterpenos , Triterpenos/análisis , China
20.
World Neurosurg ; 184: e397-e407, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38307195

RESUMEN

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.

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