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1.
Int J Biol Macromol ; 276(Pt 1): 133826, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39002908

RESUMEN

Cotton gauze is commonly used in initial emergency care. However, its high hydrophilicity and limited clotting capacity can lead to the excessive absorption of blood, resulting in unnecessary blood loss. Herein, an amphiphilic Janus cotton gauze with excellent moisture management and enhanced blood coagulation has been developed via in situ generating bioactive glass (BG) onto the cotton gauze (CG), and then attaching cardanol (CA) onto one side of the BG-loaded CG (CG@BG) via click reaction. The Janus gauze (CA-CG@BG) has asymmetric wetting properties with a hydrophilic side (CA-CG@BGHL) and a hydrophobic side (HBCA-CG@BG). When applied to hemostatic, the porous and active BG on CA-CG@BGHL can rapidly initiate coagulation cascade to form a robust thrombus. CA on HBCA-CG@BG can entangled with each other, creating a hydrophobic barrier that prevents blood from flowing out. The hemostatic performance of CA-CG@BG is superior to that of CG in both rats and pigs. Interestingly, CA-CG@BG possesses unidirectional exudate removal. When applied to wound healing, the exudate can penetrate the hydrophobic HBCA-CG@BG to the hydrophilic CA-CG@BGHL, resulting in faster wound healing than CG. CA-CG@BG exhibits excellent cytocompatibility and hemocompatibility. This unique Janus dressing shows promise as a potential material for clinical applications in the future.

2.
J Environ Manage ; 365: 121667, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38959776

RESUMEN

Implementing a Carbon Peak Action Plan at the regional level requires comprehensive consideration of the developmental heterogeneity among different provinces, which is an effective pathway for China to realize the goal of carbon peak by 2030. However, there is currently no clear provincial roadmap for carbon peak, and existing studies on carbon peak pathways inadequately address provincial heterogeneity. Therefore, this paper employs the Stochastic Impacts by Regression on Population, Affluence, and Technology (STIRPAT) model to decompose assess 8 factors influencing carbon emissions of 30 provinces. According to scenario analysis, the paper explores the differentiated pathways for provincial carbon peaks based on policy expectation indicators (including population, economy, and urbanization rate) and comprises policy control indicators (including the energy structure, energy efficiency, industrial structure, transportation structure, and innovation input). The results indicate that population, per capita GDP, urbanization rate, and innovation input are the primary factors for influencing (negatively) the growth of carbon emissions. In contrast, the optimization and upgrading of the industrial structure, energy intensity, energy structure, and transportation structure have mitigating effects on carbon emissions, especially for the first two factors. The forecasting results reveal that robust regulations of the energy and industry can effectively accelerate carbon peak at a reduced magnitude. If developed at BAU, China cannot achieve carbon peak by 2030, continuing an upward trend. However, by maximizing the adjustment strength of energy and industrial transformation within the scope of provincial capabilities, China could achieve carbon peak as early as 2025, with a peak of 12.069 billion tons. In this scenario, 24 provinces could achieve carbon peak before 2030. Overall, this study suggests the feasibility of differentiated pathway to achieve carbon peaks in China, exploring the carbon peak potential and paths of 30 provinces, and identifying provinces where carbon peak is more challenging. It also provides a reference for the design of carbon peak roadmaps at both provincial and national levels and offers targeted recommendations for the implementation of differentiated policy strategies for the government.


Asunto(s)
Dióxido de Carbono , Urbanización , China , Dióxido de Carbono/análisis , Carbono
3.
Plants (Basel) ; 13(13)2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38999588

RESUMEN

BACKGROUND: DNA methylation can change rapidly to regulate the expression of stress-responsive genes. Previous studies have shown that there are significant differences in the cold resistance of winter rapeseed (Brassica rapa L.) after being domesticated in different selection environments; however, little is known about the epigenetic regulatory mechanisms of its cold resistance formation. METHODS: Four winter rapeseed materials ('CT-2360', 'MXW-1', '2018-FJT', and 'DT-7') domesticated in different environments were selected to analyze the DNA methylation level and pattern changes under low temperature using methylation-sensitive amplified polymorphism technology with 60 primer pairs. RESULTS: A total of 18 pairs of primers with good polymorphism were screened, and 1426 clear bands were amplified, with 594 methylation sites, accounting for 41.65% of the total amplified bands. The total methylation ratios of the four materials were reduced after low-temperature treatment, in which the DNA methylation level of 'CT-2360' was higher than that of the other three materials; the analysis of methylation patterns revealed that the degree of demethylation was higher than that of methylation in 'MXW-1', '2018-FJT', and 'DT-7', which were 22.99%, 19.77%, and 24.35%, respectively, and that the methylation events in 'CT-2360' were predominantly dominant at 22.95%. Fifty-three polymorphic methylated DNA fragments were randomly selected and further analyzed, and twenty-nine of the cloned fragments were homologous to genes with known functions. The candidate genes VQ22 and LOC103871127 verified the existence of different expressive patterns before and after low-temperature treatment. CONCLUSIONS: Our work implies the critical role of DNA methylation in the formation of cold resistance in winter rapeseed. These results provide a comprehensive insight into the adaptation epigenetic regulatory mechanism of Brassica rapa L. to low temperature, and the identified differentially methylated genes can also be used as important genetic resources for the multilateral breeding of winter-resistant varieties.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39038348

RESUMEN

Context: Man-made disasters and natural disasters bring huge losses to human life and property. High-quality nursing teams play an important role in reducing casualty and disability rates in disaster areas, reducing the prognosis of the injured, accelerating community recovery and even promoting social rehabilitation. This work aimed to analyze the current situation and influencing factors of disaster emergency rescue (DER) of nurses in Hunan Province by surveying their knowledge, attitude, and practice of DER in Grade A hospitals. Methods: 1260 nurses working in 13 Grade A hospitals in Hunan Province from March to October 2022 were selected as subjects by a random sampling method and conducted by a questionnaire survey. The general data of the subjects were collected by "behaviors", forming the "nurses' knowledge, attitude, and practice questionnaire, and their DER knowledge, attitude and behavior were evaluated. Results: 1260 questionnaires were distributed, and 1,256 were effectively received, with a recovery rate of 99.68%. The total score of DER-related knowledge of 1.256 investigators was 136.82 ± 9.73 points. Among them, the highest and lowest scores were observed in the Triage (26.79 ± 2.09 points) and the sanitary and anti-epidemic (17.97 ± 1.28 points). The scores of DER attitude of 1256 respondents were close, which were arranged as about 3.87 ± 0.39 (with a range of 4.34 ~ 4.20). 1,256 investigators expressed the highest score in participating in the DER-related courses (4.93 ± 0.34 points) and the lowest score in participating in the on-site DER (2.01 ± 0.13 points). The results showed that they were correlated with gender, educational background, working years, department, and out-of-hospital emergency rescue experience (P ≤ .05), but not with age. The scores of DER-related knowledge and behaviors of hospital nurses were higher in men than in women. The higher the education, the higher the score, and the more the working years. Emergency and ICU nurses scored higher than those in other general departments. In addition, nurses with out-of-hospital emergency rescue experience scored higher than those without. Conclusion: The overall DER-related knowledge, attitude, and practice of hospital nurses is not high. Nursing managers should incorporate disaster nursing into emergency rescue nurses' training, strengthen clinical nurses' training and exercise in DER-related knowledge, pay special attention to DER drills and practices, and provide reasonable and correct DER guidance. Furthermore, it should cultivate the noble social citizenship qualities of clinical nursing nurses, such as the sense of mission to save the dying and heal the injured, the sense of satisfaction in realizing self-worth, and the sense of social responsibility. In addition, it is suggested that a reasonable incentive and reward system be established to encourage hospital nurses to participate in the DER. Due to the limitations of this study, the sample size can be expanded and included in the nurse interview considered in the future to supplement the survey data and further study and analyze nurses' rescue mentality, cognitive influencing factors, and intervention measures to provide more reference for human resource reserve and management of disaster rescue care.

5.
World J Clin Cases ; 12(20): 4057-4064, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39015897

RESUMEN

BACKGROUND: Psychological factors such as anxiety and depression will not only aggravate the symptoms of chronic obstructive pulmonary disease (COPD) patients and reduce the quality of life of patients, but also affect the treatment effect and long-term prognosis. Therefore, it is of great significance to explore the clinical application of senile comprehensive assessment in the treatment of COPD and its influence on psychological factors such as anxiety and depression. AIM: To explore the clinical application of comprehensive geriatric assessment in COPD care and its impact on anxiety and depression in elderly patents. METHODS: In this retrospective study, 60 patients with COPD who were hospitalized in our hospital from 2019 to 2020 were randomly divided into two groups with 30 patients in each group. The control group was given routine nursing, and the observation group was given comprehensive assessment. Clinical symptoms, quality of life [COPD assessment test (CAT) score], anxiety and depression Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) were compared between the two groups. RESULTS: CAT scores in the observation group decreased from an average of 24.5 points at admission to an average of 18.3 points at discharge, and in the control group from an average of 24.7 points at admission to an average of 18.3 points at discharge. The average score was 22.1 (P < 0.05). In the observation group, HAMA scores decreased from 14.2 points at admission to 8.6 points at discharge, and HAMD scores decreased from 13.8 points at admission to 7.4 points at discharge. The mean HAMD scores in the control group decreased from an average of 14.5 at admission to an average of 12.3 at discharge, and from an average of 14.1 at admission to an average of 11.8 at discharge. CONCLUSION: The application of comprehensive geriatric assessment in COPD care has a significant effect on improving patients' clinical symptoms and quality of life, and can effectively reduce patients' anxiety and depression.

6.
Patient Prefer Adherence ; 18: 1271-1280, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933236

RESUMEN

Objective: This study aimed to analyse the impact of enterostomal therapist-led visual health education combined with peer education on the postoperative self-nursing ability, quality of life and peristomial complications in patients with a permanent colostomy. Methods: Patients with a permanent colostomy admitted to Second Hospital of Hebei Medical University between March 2021 and March 2023 were selected and divided into the study group (60 patients) and the control group (60 patients). Enterostomal therapist-led visual health education combined with peer education was adopted in the study group, and regular education was adopted in the control group. The clinical effects between the two groups were compared. Results: Repeated measurement analysis of variance showed that the two educational methods had different effects on the quality of life (Ftreatment = 342.734, p < 0.001), self-nursing ability (Ftreatment = 256.321, p < 0.001), adaptability (Ftreatment = 321.734, p < 0.001) of patients with a permanent colostomy. After the 3-month intervention, the differences in all aspects of the quality of life, self-nursing ability and adaptability between the two groups were statistically significant, and the score of the study group was higher than that of the control group (p < 0.05). Compared with the control group, the study group had a lower incidence of the five complications (p < 0.05) and higher nursing satisfaction (Z = -2.968, p < 0.05). Conclusion: Enterostomal therapist-led visual health education combined with peer education can improve the quality of life of patients with a permanent colostomy, improve their positive mood, reduce their negative mood, improve their adaptability to the stoma, reduce complications and improve their daily living conditions. In the future, the clinical application of visual health education and peer education in patients with permanent colostomy should be increased.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38940288

RESUMEN

Extreme cold exposure has been widely considered as a cardiac stress and may result in cardiac function decompensation. This study was to examine the risk factors that contribute to changes in cardiovascular indicators of cardiac function following extreme cold exposure and to provide valuable insights into the preservation of cardiac function and the cardiac adaptation that occur in real-world cold environment. Seventy subjects were exposed to cold outside (Mohe, mean temperature -17 to -34°C) for one day, and were monitored by a 24-h ambulatory blood pressure device and underwent echocardiography examination before and after extreme cold exposure. After exposure to extreme cold, 41 subjects exhibited an increase in ejection fraction (EF), while 29 subjects experienced a decrease. Subjects with elevated EF had lower baseline coefficients of variation (CV) in blood pressure compared to those in the EF decrease group. Additionally, the average real variability (ARV) of blood pressure was also significantly lower in the EF increase group. Multivariate regression analysis indicated that both baseline CV and ARV of blood pressure were independent risk factors for EF decrease, and both indicators proved effective for prognostic evaluation. Correlation analysis revealed a correlation between baseline blood pressure CV and ARV, as well as EF variation after exposure to extreme cold environment. Our research clearly indicated that baseline cardiovascular indicators were closely associated with the changes in EF after extreme cold exposure. Furthermore, baseline blood pressure variability could effectively predict alterations in left cardiac functions when individuals were exposed to extreme cold environment.

8.
Nat Commun ; 15(1): 5155, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886411

RESUMEN

Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, the same mutants recurrently disrupt broad H3K27me3 domains in the chromatin context, including near developmentally regulated promoters. H3K27me3 loss leads to de-repression of differentiation pathways, with concordant effects between H3R2 and H3R26 mutants despite different proximity to the PRC2 substrate, H3K27. Functionally, H3R26C-expressing mesenchymal progenitor cells and murine embryonic stem cell-derived teratomas demonstrate impaired differentiation. Collectively, these data show that cancer-associated H3 N-terminal arginine mutations reduce PRC2 activity and disrupt chromatin-dependent developmental functions, a cancer-relevant phenotype.


Asunto(s)
Arginina , Diferenciación Celular , Histonas , Mutación , Neoplasias , Complejo Represivo Polycomb 2 , Histonas/metabolismo , Histonas/genética , Diferenciación Celular/genética , Arginina/metabolismo , Animales , Humanos , Ratones , Complejo Represivo Polycomb 2/metabolismo , Complejo Represivo Polycomb 2/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Cromatina/metabolismo , Epigénesis Genética , Células Madre Mesenquimatosas/metabolismo , Línea Celular Tumoral
9.
Biomedicines ; 12(6)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38927521

RESUMEN

Postprandial glucose levels between 4 and 7.9 h (PPG4-7.9h) correlate with mortality from various diseases, including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4-7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4-7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4-7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4-7.9h predicted using this model. A receiver operating characteristic curve analysis showed that predicted PPG4-7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. A simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4-7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4-7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

10.
Acta Pharmacol Sin ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834683

RESUMEN

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

11.
Medicine (Baltimore) ; 103(23): e38230, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847674

RESUMEN

The prognosis of acromelanomas (AM) is worse. The objective of this study was to investigate the clinical features of distant metastasis of AM and the factors affecting the survival and prognosis of patients. In this study, a retrospective study was conducted to select 154 AM patients admitted to Nanjing Pukou People's Hospital from January 2018 to April 2021 for clinical research. The clinical characteristics of distant metastasis were statistically analyzed, and the survival curve was drawn with 5-year follow-up outcomes. The median survival time of the patients was calculated, and the clinicopathological features and peripheral blood laboratory indexes of the surviving and dead patients were analyzed. Logistic regression model was used to analyze the risk factors affecting the prognosis of AM patients. In this study, 154 patients with AM were treated, including 88 males and 76 females, aged from 27 to 79 years old, with an average age of (59.3 ±â€…11.7) years old. Among them, 90 cases had distant metastasis. The main metastatic sites were lung (47.78%) and lymph nodes (42.22%). Among them, single site metastasis accounted for 41.11% and multiple site metastasis 58.89%. 89 cases survived and 65 cases died. The survival time was 22 months to 60 months, and the median survival time was 48.0 months. The Breslow thickness, stage at diagnosis, distant metastasis, site of metastasis and ulceration were compared between the survival group and the death group (P < .05). serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were compared between the survival group and the death group (P < .05). The results of Logistic regression model showed that LDH ≥ 281 U/L, NLR ≥ 2.96, LMR ≤ 3.57, newly diagnosed stage > stage II, distant metastasis, multiple site metastasis and tumor ulcer were independent risk factors for poor prognosis of AM patients (P < .05). Patients with AM had a higher proportion of distant metastasis, mainly lung and lymph node metastasis. Increased LDH, increased NLR, decreased LMR, higher initial stage, distant metastasis, multiple site metastasis, and combined tumor ulcer were closely related to the poor prognosis of patients after surgery.


Asunto(s)
Neoplasias Pulmonares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Metástasis Linfática , Metástasis de la Neoplasia , China/epidemiología
12.
Cell Death Dis ; 15(6): 390, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830885

RESUMEN

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.


Asunto(s)
Progresión de la Enfermedad , Glioma , Ribonucleoproteína Heterogénea-Nuclear Grupo C , Quinasas Asociadas a Receptores de Interleucina-1 , Sistema de Señalización de MAP Quinasas , ARN Mensajero , Humanos , Glioma/genética , Glioma/patología , Glioma/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo C/genética , Línea Celular Tumoral , Sistema de Señalización de MAP Quinasas/genética , Ratones , Estabilidad del ARN/genética , Ratones Desnudos , Animales , Regulación Neoplásica de la Expresión Génica , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Femenino , Masculino , Adenosina/análogos & derivados , Adenosina/metabolismo , Pronóstico
13.
Crit Rev Immunol ; 44(6): 87-98, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38848296

RESUMEN

In this study, network pharmacology combined with biological experimental verification was utilized to screen the targets of isoforskolin (ISOF) and investigate the potential underlying mechanism of ISOF against asthma. Asthma-related targets were screened from the Genecards and DisGeNET databases. SEA and Super-PRED databases were used to obtain the targets of ISOF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to identify enriched regulatory pathways of key targets in ISOF acting on asthma. Then, a protein-protein interaction (PPI) network was constructed via STRING database and hub genes of ISOF against asthma were further screened using molecular docking. Finally, CCK-8, qPCR, and Western blotting were performed to confirm the targets of ISOF in treating asthma. A total of 96 drug potential therapeutic targets from the relevant databases were screened out. KEGG pathway enrichment analysis predicted that the target genes might be involved in the PI3K-Akt pathway. The core targets of ISOF in treating asthma were identified by the PPI network and molecular docking, including MAPK1, mTOR, and NFKB1. Consistently, in vitro experiments showed that ISOF acting on asthma was involved in inflammatory response by reducing the expression of MAPK1, mTOR, and NFKB1. The present study reveals that MAPK1, mTOR, and NFKB1 might be key targets of ISOF in asthma treatment and the anti-asthma effect might be related to the PI3K-AKT signaling pathway.


Asunto(s)
Asma , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapas de Interacción de Proteínas , Asma/tratamiento farmacológico , Asma/metabolismo , Humanos , Animales , Ratones , Transducción de Señal/efectos de los fármacos , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo
14.
Anal Bioanal Chem ; 416(18): 4123-4130, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38782781

RESUMEN

Detection of specific gene mutations in cell-free DNA (cfDNA) serves as a valuable cancer biomarker and is increasingly being explored as an appealing alternative to tissue-based methods. However, the lack of available reference materials poses challenges in accurately evaluating the performance of different assays. In this study, we present the development of a comprehensive reference material panel for cfDNA detection, encompassing nine hotspot mutations in KRAS/BRAF/EGFR/PIK3CA at three variant allele frequencies (VAFs), ranging from 0.33 to 23.9%. To mimic cfDNA, these reference materials were generated by enzymatically digesting cell-line DNA into approximately 154-bp to 173-bp fragments using a laboratory-developed reaction system. The VAFs for each variation were precisely determined through validated digital PCR assays with high accuracy. Furthermore, the reliability and applicability of this panel were confirmed through two independent NGS assays, yielding concordant results. Collectively, our findings suggest that this novel reference material panel holds great potential for validation, evaluation, and quality control processes associated with liquid biopsy assays.


Asunto(s)
Ácidos Nucleicos Libres de Células , Proteínas Proto-Oncogénicas B-raf , Estándares de Referencia , Humanos , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/análisis , Ácidos Nucleicos Libres de Células/sangre , Proteínas Proto-Oncogénicas B-raf/genética , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genética , Reproducibilidad de los Resultados , Fosfatidilinositol 3-Quinasa Clase I/genética , Receptores ErbB/genética , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/normas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Biopsia Líquida/métodos , Biopsia Líquida/normas , Línea Celular Tumoral , Frecuencia de los Genes
15.
Chem Biodivers ; : e202302059, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38736027

RESUMEN

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

16.
Radiother Oncol ; 197: 110340, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38797492

RESUMEN

PURPOSE: This study aimed to reveal the association of fatigue with weekly changes in the body composition in patients with nasopharyngeal carcinoma (NPC) and identified the independent strength. METHODS: Four body composition indexes and fatigue were assessed before treatment (T0, baseline) and once a week throughout radiotherapy (T1-T7). Generalized additive mixed models (GAMMs) were used to explore the trajectories and longitudinal relationships of fatigue and weekly changes in body composition. The marginal structural model (MSM) was used to control the effect of depression and anxiety. RESULTS: The trajectories of fatigue in 105 participants reached a peak in the fifth week, and changes in body composition started appearing from the second week. Four body composition indexes, weight, body mass index (BMI), body fat rate, and lean body weight loss weekly were positively associated with fatigue. High magnitude of effects was revealed when anxiety and depression were controlled as time-dependent confounders. The positive associations with fatigue were manifested in patients aged >53 years, those with senior high and above education, no drinking, >5000 Y/month of family inflow, ≥ stage III, or those receiving a dose of ≥70 Gy, ≥3 cycles of induced chemotherapy, and ≤1 cycle of concurrent chemotherapy. CONCLUSIONS: Loss of weight, BMI, body fat rate, and lean body weight could be used to independently evaluate the development of fatigue in patients with NPC during radiotherapy. Positive associations between fatigue and weekly body composition loss were found in patients with certain characteristics.


Asunto(s)
Composición Corporal , Fatiga , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Fatiga/etiología , Estudios Longitudinales , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Adulto , Índice de Masa Corporal , Anciano , Pérdida de Peso
17.
Biomacromolecules ; 25(6): 3335-3344, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38717974

RESUMEN

Hemostatic powder is widely employed for emergency bleeding control due to its ability to conform to irregularly shaped wounds, ease of use, and stable storage. However, current powders exhibit limited tissue adhesion and insufficient support for thrombus formation, making them easily washed away by blood. In this study, a hybrid powder (QAL) was produced by mixing quaternized chitosan (QCS) powder, catechol-modified alginate (Cat-SA) powder, and laponite (Lap) powder. Upon addition of QAL, the blood quickly transformed to a robust and adhesive blood gel. The adhesion strength of the blood gel was up to 31.33 ± 1.56 kPa. When compared with Celox, QAL showed superior performance in promoting hemostasis. Additionally, QAL exhibited effectiveness in eliminating bacteria while also demonstrating outstanding biocompatibility with cells and blood. These favorable properties, including strong coagulation, adhesion to wet tissue, antibacterial activity, biosafety, ease of use, and stable storage, make QAL a promising emergency hemostatic agent.


Asunto(s)
Alginatos , Coagulación Sanguínea , Quitosano , Hemostáticos , Polvos , Silicatos , Hemostáticos/química , Hemostáticos/farmacología , Silicatos/química , Animales , Coagulación Sanguínea/efectos de los fármacos , Polvos/química , Quitosano/química , Alginatos/química , Alginatos/farmacología , Humanos , Ratones , Geles/química , Polisacáridos/química , Polisacáridos/farmacología , Hemostasis/efectos de los fármacos
18.
ACS Appl Bio Mater ; 7(6): 3758-3765, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38768375

RESUMEN

Drug-resistant bacteria present a grave threat to human health. Fluorescence imaging-guided photodynamic antibacterial therapy holds enormous potential as an innovative treatment in antibacterial therapy. However, the development of a fluorescent material with good water solubility, large Stokes shift, bacterial identification, and high photodynamic antibacterial efficiency remains challenging. In this study, we successfully synthesized an amphiphilic aggregation-induced emission (AIE) fluorescent probe referred to as NPTPA-QM. This probe possesses the ability to perform live-bacteria fluorescence imaging while also exhibiting antibacterial activity, specifically against Staphylococcus aureus (S. aureus). We demonstrate that NPTPA-QM can eliminate S. aureus at a very low concentration (2 µmol L-1). Moreover, it can effectively promote skin wound healing. Meanwhile, this NPTPA-QM exhibits an excellent imaging ability by simple mixing with S. aureus. In summary, this research presents a straightforward and highly effective method for creating "amphiphilic" AIE fluorescent probes with antibacterial properties. Additionally, it offers a rapid approach for imaging bacteria utilizing red emission.


Asunto(s)
Antibacterianos , Materiales Biocompatibles , Colorantes Fluorescentes , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Imagen Óptica , Tamaño de la Partícula , Staphylococcus aureus , Staphylococcus aureus/efectos de los fármacos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/farmacología , Colorantes Fluorescentes/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Estructura Molecular , Ratones , Animales , Humanos , Tensoactivos/química , Tensoactivos/farmacología , Tensoactivos/síntesis química
19.
Int J Biol Macromol ; 271(Pt 2): 132559, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38821802

RESUMEN

Massive bleeding resulting from civil and martial accidents can often lead to shock or even death, highlighting the critical need for the development of rapid and efficient hemostatic materials. While various types of hemostatic materials are currently utilized in clinical practice, they often come with limitations such as poor biocompatibility, toxicity, and biodegradability. Polysaccharides, such as alginate (AG), chitosan (CS), cellulose, starch, hyaluronic acid (HA), and dextran, have exhibit excellent biocompatibility and in vivo biodegradability. Their degradation products are non-toxic to surrounding tissues and can be absorbed by the body. As a result, polysaccharides have been extensively utilized in the development of hemostatic materials and have gained significant attention in the field of in vivo hemostasis. This review offers an overview of the different forms, hemostatic mechanisms, and specific applications of polysaccharides. Additionally, it discusses the future opportunities and challenges associated with polysaccharide-based hemostats.


Asunto(s)
Materiales Biocompatibles , Hemostáticos , Polisacáridos , Polisacáridos/química , Hemostáticos/química , Hemostáticos/farmacología , Hemostáticos/uso terapéutico , Humanos , Animales , Materiales Biocompatibles/química , Hemostasis/efectos de los fármacos , Quitosano/química , Hemorragia/tratamiento farmacológico
20.
Int J Biol Macromol ; 270(Pt 2): 132440, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38761899

RESUMEN

Hemostatic powder is widely utilized in emergency situations to control bleeding due to its ability to work well on wounds with irregular shapes, ease of application, and long-term stability. However, traditional powder often suffers from limited tissue adhesion and insufficient support for blood clot formation, leaving it susceptible to displacement by the flow of blood. This study introduces a hemostatic powder composed of tannic modified mesoporous bioactive glass (TMBG), cationic quaternized chitosan (QCS), and anionic hyaluronic acid modified with catechol group (HADA). The resulting TMBG/QCS/HADA based hemostatic powder (TMQH) rapidly absorbs plasma, concentrating blood coagulation factors. Simultaneously, the water-soluble QCS and HADA interact to form a 3D network structure, which can be strengthened by crosslinking with TMBG. This network effectively captures clustered blood coagulation factors, leading to a strong and adhesive thrombus that resists disruption from blood flow. TMQH exhibits superior efficacy in promoting hemostasis compared to Celox™ both in rat arterial injuries and non-compressible liver puncture wounds. TMQH demonstrates excellent antibacterial activity, cytocompatibility, and blood compatibility. These outstanding superiorities in blood clotting capability, wet tissue adhesion, antibacterial activity, safety for living organisms, ease of application, and long-term stability, make TMQH highly suitable for emergency hemostasis.


Asunto(s)
Coagulación Sanguínea , Hemostáticos , Polvos , Taninos , Animales , Ratas , Coagulación Sanguínea/efectos de los fármacos , Taninos/química , Taninos/farmacología , Hemostáticos/química , Hemostáticos/farmacología , Porosidad , Vidrio/química , Polisacáridos/química , Polisacáridos/farmacología , Quitosano/química , Quitosano/farmacología , Geles/química , Humanos , Adhesivos/química , Adhesivos/farmacología , Masculino , Ratas Sprague-Dawley , Hemostasis/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
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