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2.
Cancer Commun (Lond) ; 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39003618

RESUMEN

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non-immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.

3.
Metabolism ; 158: 155957, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908508

RESUMEN

Cardiovascular diseases (CVDs) are often linked to structural and functional impairments, such as heart defects and circulatory dysfunction, leading to compromised peripheral perfusion and heightened morbidity risks. Metabolic remodeling, particularly in the context of cardiac fibrosis and inflammation, is increasingly recognized as a pivotal factor in the pathogenesis of CVDs. Metabolic syndromes further predispose individuals to these conditions, underscoring the need to elucidate the metabolic underpinnings of CVDs. Lactate, a byproduct of glycolysis, is now recognized as a key molecule that connects cellular metabolism with the regulation of cellular activity. The transport of lactate between different cells is essential for metabolic homeostasis and signal transduction. Disruptions to lactate dynamics are implicated in various CVDs. Furthermore, lactylation, a novel post-translational modification, has been identified in cardiac cells, where it influences protein function and gene expression, thereby playing a significant role in CVD pathogenesis. In this review, we summarized recent advancements in understanding the role of lactate and lactylation in CVDs, offering fresh insights that could guide future research directions and therapeutic interventions. The potential of lactate metabolism and lactylation as innovative therapeutic targets for CVD is a promising avenue for exploration.

4.
ACS Appl Mater Interfaces ; 16(25): 32713-32726, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38860983

RESUMEN

Metal-organic frameworks (MOFs) have attracted attention due to their designable structures. However, recently reported MOF microwave-absorbing materials (MAMs) are dominated by powders. It remains a challenge to design MOF/carbon nanotube (CNT) composite structures that combine the mechanical properties of self-supporting flexibility with excellent microwave absorption. This work involves the hydrothermal approach to grow Ni-MOF of different microstructures in situ on the CNT monofilament by adjusting the molar ratio of nickel ions to organic ligands. Subsequently, an ultraflexible self-supporting Ni-MOF/CNT buckypaper (BP) is obtained by directional gas pressure filtration technology. The BP porous skeleton and the Ni-MOF with a unique porous structure provide effective impedance matching. The CNTs contribute to the conduction loss, the cross-scale heterogeneous interface generated by Ni-MOF/CNT BP provides rich interfacial polarization loss, and the porous structure complicates the microwave propagation path. All factors work together to give Ni-MOF/CNT BP an excellent microwave absorption capacity. The minimum reflection losses of Ni-MOF/CNT BPs decorated with granular-, hollow porous prism-, and porous prism-shaped Ni-MOFs reach -50.8, -57.8, and -43.3 dB, respectively. The corresponding effective absorption bandwidths are 4.5, 6.3, and 4.8 GHz, respectively. Furthermore, BPs show remarkable flexibility as they can be wound hundreds of times around a glass rod with a diameter of 4 mm without structural damage. This work presents a new concept for creating ultraflexible self-supported MOF-based MAMs with hierarchical interpenetrating porous structures, with potential application advantages in the field of flexible electronics.

5.
Medicine (Baltimore) ; 103(21): e38032, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38788041

RESUMEN

BACKGROUND: Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE. METHODS: Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software. RESULTS: A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RR = 1.40, 95%CI: 1.33 ~ 1.46, P < .001). And the combined use of LNT could increase the quality of life (RR = 1.45, 95%CI: 1.35 ~ 1.56, P < .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RR = 0.86, 95%CI: 0.78 ~ 0.94, P < .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias. CONCLUSIONS: Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.


Asunto(s)
Antineoplásicos , Cisplatino , Lentinano , Derrame Pleural Maligno , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Derrame Pleural Maligno/tratamiento farmacológico , Lentinano/administración & dosificación , Lentinano/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Resultado del Tratamiento
6.
Int Immunopharmacol ; 133: 112072, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38636371

RESUMEN

OBJECTIVE: This study aimed to investigate the role of KLRB1 (CD161) in human CD4+ T cells and elucidate its significance in primary Sjögren's syndrome (pSS). METHODS: Peripheral blood samples from 37 healthy controls and 44 pSS patients were collected. The publicly available single-cell RNA-Seq data from pSS patient PBMCs were utilized to analyse KLRB1 expression in T cells. KLRB1-expressing T lymphocyte subset proportions in pSS patients and healthy controls were determined by flow cytometry. CD25, Ki-67, cytokine secretion, and chemokine receptor expression in CD4+ KLRB1+ T cells were detected and compared with those in CD4+ KLRB1- T cells. Correlation analysis was conducted between KLRB1-related T-cell subsets and clinical indicators. ROC curves were generated to explore the diagnostic potential of KLRB1 for pSS. RESULTS: KLRB1 was significantly upregulated following T-cell activation, and Ki-67 and CD25 expression was significantly greater in CD4+ KLRB1+ T cells than in CD4+ KLRB1- T cells. KLRB1+ CD4+ T cells exhibited greater IL-17A, IL-21, IL-22, and IFN-γ secretion upon stimulation, and there were significantly greater proportions of CCR5+, CCR2+, CX3CR1+, CCR6+, and CXCR3+ cells among CD4+ KLRB1+ T cells than among CD4+ KLRB1- T cells. Compared with that in HCs, KLRB1 expression in CD4+ T cells was markedly elevated in pSS patients and significantly correlated with clinical disease indicators. CONCLUSION: KLRB1 is a characteristic molecule of the CD4+ T-cell activation phenotype. The increased expression of KLRB1 in the CD4+ T cells of pSS patients suggests its potential involvement in the pathogenesis of pSS and its utility as an auxiliary diagnostic marker for pSS.


Asunto(s)
Linfocitos T CD4-Positivos , Subfamilia B de Receptores Similares a Lectina de Células NK , Síndrome de Sjögren , Regulación hacia Arriba , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T CD4-Positivos/inmunología , Citocinas/inmunología , Antígeno Ki-67/metabolismo , Activación de Linfocitos , Subfamilia B de Receptores Similares a Lectina de Células NK/genética , Subfamilia B de Receptores Similares a Lectina de Células NK/inmunología , Fenotipo , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/genética , Síndrome de Sjögren/inmunología
7.
Diagnostics (Basel) ; 14(7)2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38611678

RESUMEN

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

8.
Small ; : e2401880, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38678520

RESUMEN

Two-dimensional (2D) covalent organic frameworks (COFs) have a multilayer skeleton with a periodic π-conjugated molecular array, which can facilitate charge carrier transport within a COF layer. However, the lack of an effective charge carrier transmission pathway between 2D COF layers greatly limits their applications in electrocatalysis. Herein, by employing a side-chain polymerization strategy to form polythiophene along the nanochannels, a conjugated bridge is constructed between the COF layers. The as-synthesized fully conjugated COF (PTh-COF) exhibits high oxygen reduction reaction (ORR) activity with narrowed energy band gaps. Correspondingly, PTh-COF is tested as a metal-free cathode catalyst for anion exchange membrane fuel cells (AEMFCs) which showed a maximum power density of 176 mW cm-2 under a current density of 533 mA cm-2. The density functional theory (DFT) calculation reveals that interlayer conjugated polythiophene optimizes the electron cloud distribution, which therefore enhances the ORR performance. This work not only provides new insight into the construction of a fully conjugated covalent organic framework but also promotes the development of new metal-free ORR catalysts.

9.
Comput Biol Med ; 172: 108221, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452473

RESUMEN

BACKGROUND: Gastric carcinoma (GC) remains a significant therapeutic challenge, garnering widespread attention. Oxymatrine (OMT), an active component of the traditional Chinese medicine compound Kushen injection (CKI), has shown promising results in combination with chemotherapy for the treatment of GC. However, the molecular mechanisms underlying OMT's therapeutic effects in GC have yet to be elucidated. METHODS: The transcriptomic expression data of HGC-27 post-OMT intervention were obtained through microarray sequencing, while the miRNA and mRNA sequencing data for GC patients were sourced from the TCGA database. The mechanism of OMT intervention in GC is analyzed in multiple aspects, including Protein-Protein Interactions (PPI), Competitive Endogenous RNA (ceRNA) networks, correlation and co-expression analyses, immune infiltration, and clinical implications. RESULTS: By analyzing key modules, five critical mRNAs were identified, and their interacting miRNAs were predicted to construct a ceRNA network. Among these, TGFBR2 and hsa-miR-107 have correlations or co-expression relationships with other genes in the network. They are differentially expressed in most other cancers, associated with prognosis, and have diagnostic value. TGFBR2 also exhibits immune infiltration phenomena, and its high expression is linked to poor patient prognosis. Low expression of hsa-miR-107 is associated with poor patient prognosis. OMT may act on the TGFß/Smad signaling pathway or negatively regulate the WNT signaling pathway through the hsa-miR-107/BTRC axis, thereby inhibiting the onset and progression of GC. CONCLUSION: The mechanisms of OMT intervention in GC are diverse, TGFBR2 and hsa-miR-107 may serve as prognostic molecular biomarkers or potential therapeutic targets.


Asunto(s)
MicroARNs , Neoplasias Gástricas , Humanos , Biología Computacional/métodos , MicroARNs/genética , MicroARNs/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , ARN Mensajero/genética , Neoplasias Gástricas/genética
10.
Heliyon ; 10(6): e27551, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38510032

RESUMEN

Introduction: Whether the hypertension burden is associated with stroke incidence is inconclusive. In this study, we aimed to investigate the relationship between hypertension burden and stroke risk in patients with heart failure with preserved ejection fraction (HFpEF). Methods: HFpEF patients from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were divided into three groups (low, medium, and high risk) according to their hypertension burden values. Higher hypertension burden risk represented the longer duration of hypertension. We evaluated the association of hypertension burden with stroke risk using Fine and Gray's competing risk models. Results: A total of 3431 HFpEF patients (mean age: 68.5 ± 9.58 years, 51.6% females) were enrolled. During a median follow-up of 3.3 years, per 10-point increase in hypertension burden was associated with any stroke (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.21), new-onset stroke (HR 1.14, 95% CI 1.07-1.21), and ischemic stroke (HR 1.10, 95% CI 1.02-1.17). When hypertension burden was analyzed as a categorical variable, any stroke risk was increased in the medium- (HR 1.59, 95% CI 1.01-2.40) and high-risk (HR 3.19, 95% CI 2.05-4.97) groups when compared with the low-risk group. For the outcomes of new-onset (HR 2.92, 95% CI 1.80-4.74) and ischemic stroke (HR 2.46, 95% CI 1.41-4.29), similar results were observed in patients with high-versus low-risk hypertension burden. Conclusions: Increasing hypertension burden was associated with an increased risk of stroke, suggesting that shortening hypertension duration might appropriately minimize the stroke incidence in HFpEF patients.

11.
Biotechnol J ; 19(2): e2300542, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38403404

RESUMEN

Bacterial second messenger c-di-GMP upregulation is associated with the transition from planktonic to sessile microbial lifestyle, inhibiting cellular motility, and virulence. However, in-depth elucidation of the cellular processes resulting from c-di-GMP upregulation has not been fully explored. Here, we report the role of upregulated cellular c-di-GMP in promoting planktonic cell growth of Escherichia coli K12 and Pseudomonas aeruginosa PAO1. We found a rapid expansion of cellular growth during initial cellular c-di-GMP upregulation, resulting in a larger planktonic bacterial population. The initial increase in c-di-GMP levels promotes bacterial swarming motility during the growth phase, which is subsequently inhibited by the continuous increase of c-di-GMP, and ultimately facilitates the formation of biofilms. We demonstrated that c-di-GMP upregulation triggers key bacterial genes linked to bacterial growth, swarming motility, and biofilm formation. These genes are mainly controlled by the master regulatory genes csgD and csrA. This study provides us a glimpse of the bacterial behavior of evading potential threats through adapting lifestyle changes via c-di-GMP regulation.


Asunto(s)
Proteínas Bacterianas , GMP Cíclico/análogos & derivados , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación hacia Arriba , Biopelículas , Regulación Bacteriana de la Expresión Génica , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo
12.
ACS Appl Mater Interfaces ; 16(7): 8459-8473, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38327180

RESUMEN

Metal-organic frameworks (MOFs) are emerging porous materials that can serve as carriers of photosensitizers and photothermal agents. Meanwhile, a large number of active sites in MOFs endow them with the characteristics of modification by postsynthetic modification. Herein, a dual-modal PDT/PTT therapeutic agent HMIL-121-acriflavine-tetrakis (4-amoniophenyl) porphyrin (HMIL-ACF-Por), prepared by the postsynthetic modification of the MOF (HMIL-121), was reported for antibacterial applications. The prepared HMIL-ACF-Por enables the generation of abundant reactive oxygen species, including the superoxide anion radical (O2-) and singlet oxygen (1O2), and thermal energy under 808 nm NIR laser irradiation. HMIL-ACF-Por showed good antibacterial ability against Escherichia coli and Staphylococcus aureus in vitro. Meanwhile, HMIL-ACF-Por can effectively inhibit the inflammatory response caused by bacterial infection and accelerate S. aureus-infected wound healing under laser irradiation owing to the synergistic effect of photodynamic therapy (PDT) and photothermal therapy (PTT). These results demonstrate that HMIL-ACF-Por is a promising PDT/PTT therapeutic agent. This work also contributes to offering an effective solution for treating bacterial infections and promotes the application of MOF-based materials in biomedicine.


Asunto(s)
Estructuras Metalorgánicas , Fotoquimioterapia , Fotoquimioterapia/métodos , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/química , Staphylococcus aureus , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno , Superóxidos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
13.
Comput Biol Med ; 168: 107759, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38043467

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prominent form of esophageal cancer. Aurora A (AURKA), an enzyme that phosphorylates serine and threonine, has a vital function in controlling the process of separating chromosomes during cell division. The contribution of this entity has been documented in the advancement of malignant proliferations, including tumors occurring in the breast, stomach, and ovaries. METHODS: The potential molecular mechanism of AURKA is comprehensively examined through the analysis of bulk RNA-seq and single-cell RNA-seq data obtained from publicly available databases. This analysis encompasses various aspects such as expression levels, prognosis, and functional pathways, among others. RESULTS: The upregulation of AURKA in ESCC has been found to be correlated with the overall survival of patients. The functional annotation and pathway enrichment analysis conducted in this study lead to the conclusion that AURKA participates in the regulation of a number of malignant processes connected to cell proliferation, such as cell cycle control, apoptosis, and the p53 signaling pathway. Additionally, AURKA has been found to be associated with drug sensitivity and has an impact on the infiltration of tumor-infiltrating immune cells in ESCC. CONCLUSIONS: AURKA exhibits potential as a prognostic and therapeutic biomarker linked to the regulation of cell cycle and cell proliferation.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Biomarcadores , Línea Celular Tumoral , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/genética , Regulación Neoplásica de la Expresión Génica
14.
Phytomedicine ; 123: 155242, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38100922

RESUMEN

BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.


Asunto(s)
Lentinano , Neoplasias Gástricas , Humanos , Lentinano/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Resultado del Tratamiento
15.
Nat Prod Res ; : 1-6, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37874626

RESUMEN

Two new alkaloids designated aspernigrin E (1) and pyranonigrin L (2) were isolated from mangrove endophytic fungus Aspergillus fumigatus SAS10, together with the known alkaloid compounds pyranonigrin A (3), asperazine (4), (+)-iso-pestalazine A (5), pestalazine A (6), and pestalazine B (7). The planar structures of the new compounds were elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configurations of compounds 1 and 2 were determined by comparison of the electronic circular dichroic (ECD) spectra with the calculated ECD spectra. All these compounds were tested for anti-bacterial activity.

16.
Comput Biol Med ; 166: 107562, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37847945

RESUMEN

BACKGROUND: Gastric cancer is a life-threatening disease that poses a serious risk to human health. Although there are numerous molecular targets for gastric cancer in clinical practice, they often exhibit low specificity and sensitivity. Consequently, this can result in a low early diagnosis rate, delayed treatment, and poor prognosis for patients with gastric cancer. Hence, it remains crucial to identify more precise diagnostic markers for this disease. METHODS: This study utilized ceRNA chips and bioinformatics methods to investigate the key genes and mechanisms involved in matrine intervention in gastric cancer cells. RESULTS: ADAM12 and PDGFRB are the key genes that are down-regulated after matrine intervention in gastric cancer cells. By conducting bioinformatics analysis, two ceRNA regulatory axes were identified, which are associated with the prognosis of gastric cancer. These axes are lncRNA DGCR5/hsa-miR-206/ADAM12 and circRNA ITGA3/hsa-miR-24-3p/PDGFRB. CONCLUSION: The low expression of ADAM12 may weaken the digestion of extracellular matrix (ECM) molecules, which can result in the invasion and metastasis of tumor cells. This occurs without the catalysis of ECM proteases, thereby impacting the invasion and metastasis of gastric cancer cells. Additionally, the analysis of immune infiltration suggests that ADAM12 and PDGFRB may influence changes in the tumor immune microenvironment, thereby affecting the occurrence and development of gastric cancer. This study contributes to a deeper understanding of the role of the matrine-related ceRNA network in gastric cancer, providing a reference for clinical diagnosis and treatment. It holds significant importance in discovering new drug treatment targets.

17.
Medicine (Baltimore) ; 102(34): e34866, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37653800

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, leading to a pandemic. In China, Xiyanping injection (XYP) has been recommended as a drug for COVID-19 treatment in the Guideline on Diagnosis and Treatment of COVID-19 by the National Health Commission of the People Republic of China and National Administration of Traditional Chinese Medicine (Trial eighth Edition). However, the relevant mechanisms at the molecular-level need to be further elucidated. METHODS: In this study, XYP related active ingredients, potential targets and COVID-19 related genes were searched in public databases. Protein-protein interaction network and module analyzes were used to screen for key targets. gene ontology and Kyoto encyclopedia of genes and genomes were performed to investigate the potentially relevant signaling pathways. Molecular docking was performed using Autodock Tools and Vina. For the validation of potential mechanism, PolyI:C was used to induce human lung epithelial cells for an inflammation model. Subsequently, CCK-8 assays, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blot were employed to determine the effect of XYP on the expression of key genes. RESULTS: Seven effective active ingredients in XYP were searched for 123 targets in the relevant databases. Furthermore, 6446 COVID-19 disease targets were identified. Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate was identified as the vital active compounds, and IL-6, TNF, IL-1ß, CXCL8, STAT3, MAPK1, MAPK14, and MAPK8 were considered as the key targets. In addition, molecular docking revealed that the active compound and the targets showed good binding affinities. The enrichment analysis predicted that the XYP could regulate the IL-17, Toll-like receptor, PI3K-Akt and JAK-STAT signaling pathways. Consistently, further in vitro experiments demonstrated that XYP could slow down the cytokine storm in the lung tissue of COVID-19 patients by down-regulating IL-6, TNF-α, IL-1ß, CXCL8, and p-STAT3. CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos , Farmacología en Red , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Mapas de Interacción de Proteínas , Transducción de Señal , Simulación del Acoplamiento Molecular , Células Epiteliales , Células Cultivadas , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Citocinas
18.
Comput Biol Med ; 165: 107402, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37657358

RESUMEN

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Additionally, disulfidptosis, a newly discovered type of cell death, has been found to be closely associated with the onset and progression of tumors. METHODS: The study first identified genes related to disulfidptosis through correlation analysis. These genes were then screened using univariate cox regression and LASSO regression, and a prognostic model was constructed through multivariate cox regression. A nomogram was also created to predict the prognosis of LUAD. The model was validated in three independent data sets: GSE72094, GSE31210, and GSE37745. Next, patients were grouped based on their median risk score, and differentially expressed genes between the two groups were analyzed. Enrichment analysis, immune infiltration analysis, and drug sensitivity evaluation were also conducted. RESULTS: In this study, we examined 21 genes related to disulfidptosis and developed a gene signature that was found to be associated with a poorer prognosis in LUAD. Our model was validated using three independent datasets and showed AUC values greater than 0.5 at 1, 3, and 5 years. Enrichment analysis revealed that the disulfidptosis-related genes signature had a multifaceted impact on LUAD, particularly in relation to tumor development, proliferation, and metastasis. Patients in the high-risk group exhibited higher tumor purity and lower stromal score, ESTIMATE score, and Immune score. CONCLUSION: This study constructed a gene signature related to disulfidptosis in lung adenocarcinoma and analyzed its impact on the disease and its association with the tumor microenvironment. The findings of this research provide valuable insights into the understanding of lung adenocarcinoma and could potentially lead to the development of new treatment strategies.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Pronóstico , Neoplasias Pulmonares/genética , Adenocarcinoma del Pulmón/genética , Microambiente Tumoral
19.
Front Nutr ; 10: 1249639, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37671201

RESUMEN

Siraitia grosvenorii seeds are rich in abundant active compounds beneficial to human health. To clarify the digestion characteristics of Siraitia grosvenorii seed flour (SSF) and promote the use of SSF in the processing of functional staple foods, SSF was prepared, its composition and physicochemical properties were studied, and the processing characteristics of SSF-wheat flour were systematically investigated. The results showed that the torque curve and other parameters of the dough were significantly affected by the amount of SSF added. With the increase of SSF proportion, the water absorption showed an increasing trend, while the degree of protein weakening first weakened and then enhanced. At 20% SSF, the dough was more resistant to kneading. In response to an increase in SSF, the L* value decreased significantly, and the a* and b* values increased gradually, while the specific volume decreased gradually. Additionally, the hardness, adhesiveness, and chewiness of the bread enhanced gradually, while its elasticity, cohesiveness, and resilience decreased gradually. After the addition of 30% SSF, the inner tissue of steamed bread was more delicate. With an increase in SSF proportion, the predicted glycemic index (pGI) of steamed bread weakened markedly. Overall, these results showed that SSF, as a kind of food ingredient with hypoglycemic activity, can be used in the production of new functional steamed bread products. This study provides basic research data for the development of products containing S. grosvenorii seed.

20.
Mar Drugs ; 21(8)2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37623711

RESUMEN

The high molecular weight and poor solubility of seaweed polysaccharides have limited their function and application. In this study, ultraviolet/hydrogen peroxide (UV/H2O2) treatment was used to prepare low-molecular-weight seaweed polysaccharides from Sargassum fusiforme. The effects of UV/H2O2 treatment on the physicochemical properties and anti-photoaging activity of S. fusiforme polysaccharides were studied. UV/H2O2 treatment effectively degraded polysaccharides from S. fusiforme (DSFPs), reducing their molecular weight from 271 kDa to 26 kDa after 2 h treatment. The treatment did not affect the functional groups in DSFPs but changed their molar percentage of monosaccharide composition and morphology. The effects of the treatment on the anti-photoaging function of S. fusiforme polysaccharides were investigated using human epidermal HaCaT cells in vitro. DFSPs significantly improved the cell viability and hydroxyproline secretion of UVB-irradiated HaCaT cells. In particular, DSFP-45 obtained from UV/H2O2 treatment for 45 min showed the best anti-photoaging effect. Moreover, DSFP-45 significantly increased the content and expression of collagen I and decreased those of pro-inflammatory cytokines, including interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Thus, UV/H2O2 treatment could effectively improve the anti-photoaging activity of S. fusiforme polysaccharides. These results provide some insights for developing novel and efficient anti-photoaging drugs or functional foods from seaweed polysaccharides.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias Cutáneas , Humanos , Peróxido de Hidrógeno/farmacología , Supervivencia Celular , Colágeno Tipo I , Citocinas
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