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1.
World J Clin Cases ; 12(21): 4601-4608, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39070814

RESUMEN

BACKGROUND: Currently, the use of dienogest in clinical practice has increased significantly, and many studies have focused on its effectiveness and safety in the treatment of endometriosis and adenomyosis; however, the effects of treatment with dienogest on uterine fibroid size in patients with endometriosis or adenomyosis have not been investigated. AIM: To explore changes in fibroid size in patients with concomitant uterine fibroids undergoing dienogest treatment for endometriosis or adenomyosis and to evaluate the effectiveness and safety of the drug. METHODS: The clinical data of patients with uterine fibroids treated with dienogest for endometriosis or adenomyosis at Peking University First Hospital from January 2021 to January 2023 were retrospectively analyzed. RESULTS: The maximum uterine fibroid diameter and volume increased after 3 months, 6 months and 1 year of dienogest treatment compared with those before treatment (P < 0.01). The maximum diameter and volume of the uterine adenomyoma increased after 3 months of dienogest treatment but decreased after 6 months and 1 year of treatment compared with those before treatment, but the difference was not significant (P > 0.05). Endometrial thickness and antigen 125 levels were significantly thinner and decreased, respectively, after dienogest treatment (P < 0.01). Pearson's correlation analysis revealed that the increase in uterine fibroid volume after 3 months of dienogest treatment was positively correlated with the basic uterine fibroid volume (r = 0.792, P < 0.01). Among 64 patients with dysmenorrhea, 63 experienced significant relief of dysmenorrhea after 6 months of treatment with dienogest, and all patients experienced significant relief of dysmenorrhea after 12 months. Patients were able to tolerate the drugs, with an average drug tolerance score of 8.73. CONCLUSION: The use of dienogest in patients with endometriosis or adenomyosis combined with uterine fibroids can effectively relieve the patient's pain symptoms and significantly reduce the sizes of ovarian endometriotic cysts, but it cannot inhibit uterine fibroid growth.

2.
BMC Med Educ ; 24(1): 803, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39061003

RESUMEN

BACKGROUND: Digital health plays a vital role in healthcare services. Governments in many countries, including China, are increasingly advocating for the appropriate use of digital technologies to address significant health system challenges. It is crucial to incorporate digital health education into the curriculum for future nurses to adapt to the changes in the digital medical system. This study aimed to evaluate the impact of an online Digital Health and Informatics Course in China on the knowledge and comprehension of key digital health and informatics topics, self-assessment of nursing informatics competencies, and satisfaction among undergraduate nursing students. The findings of this study provide recommendations for the design and implementation of future digital health education. METHODS: This study employed a one-group, quasi-experimental mixed-methods design with pre- and post-assessments. The participants received digital health and informatics education through six three-hour online sessions in six interactive days, with online self-learning materials in between. An online quiz and focus group discussions pre- and post the course were designed to evaluate the knowledge and comprehension of key digital health and informatics topics. Also, a validated Chinese version of the Self-assessment of Nursing Informatics Competencies Scale was conducted pre- and post-course to assess self-assessment of nursing informatics competencies. Additionally, all students were invited to participate in an online survey with a performance-focused course evaluation form as well as focus group discussions to gather their feedback on the learning experience and their evaluations of the course. RESULTS: A total of 24 undergraduate nursing students were enrolled in the course. All students completed all sessions of this course, resulting in an attendance rate of 100%. Additionally, all students completed both pre- and post-assessments. In terms of the knowledge and comprehension of key digital health and informatics topics, scores of the quiz on knowledge assessment improved from the pre-test [mean pretest score: 78.33 (SD 6.005)] to the post-test [mean post-test score: 83.17 (SD 4.86)] upon completion of the course (P < 0.001). Also, students acknowledged that the course enhanced their knowledge and comprehension of informatics and digital health, the benefits of (nursing) informatics in clinical practice, and the role of health care professionals in informatics and digital health. In terms of self-assessment of nursing informatics competencies, scores on nursing informatics attitudes demonstrated significant improvement (P < 0.001). Furthermore, students reported high satisfaction with various aspects of this course, including the opportunity to explore broad horizons in informatics for future careers, engaging in group discussions, and analyzing case studies on the use of informatics and digital health in clinical practice. CONCLUSIONS: This Online Digital Health and Informatics education effectively improved undergraduate nursing students' knowledge and comprehension of the key digital health and informatics topics, nursing informatics attitudes in the self-assessment of nursing informatics competency with high levels of satisfaction. In order to ensure that future education in digital health and informatics for nursing students is in line with the technological advancements in clinical settings, it is necessary to foster collaboration between medical school training and clinical practice. This collaboration should involve the use of clinical examples to illustrate advanced digital health applications and the inclusion of practical exercises on the use of digital health technology in clinical settings.


Asunto(s)
Curriculum , Bachillerato en Enfermería , Informática Aplicada a la Enfermería , Estudiantes de Enfermería , Humanos , China , Informática Aplicada a la Enfermería/educación , Femenino , Masculino , Educación a Distancia , Adulto Joven , Adulto , Evaluación Educacional , Salud Digital
3.
J Transl Med ; 22(1): 686, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39061062

RESUMEN

BACKGROUND: During the prolonged period from Human Papillomavirus (HPV) infection to cervical cancer development, Low-Grade Squamous Intraepithelial Lesion (LSIL) stage provides a critical opportunity for cervical cancer prevention, giving the high potential for reversal in this stage. However, there is few research and a lack of clear guidelines on appropriate intervention strategies at this stage, underscoring the need for real-time prognostic predictions and personalized treatments to promote lesion reversal. METHODS: We have established a prospective cohort. Since 2018, we have been collecting clinical data and pathological images of HPV-infected patients, followed by tracking the progression of their cervical lesions. In constructing our predictive models, we applied logistic regression and six machine learning models, evaluating each model's predictive performance using metrics such as the Area Under the Curve (AUC). We also employed the SHAP method for interpretative analysis of the prediction results. Additionally, the model identifies key factors influencing the progression of the lesions. RESULTS: Model comparisons highlighted the superior performance of Random Forests (RF) and Support Vector Machines (SVM), both in clinical parameter and pathological image-based predictions. Notably, the RF model, which integrates pathological images and clinical multi-parameters, achieved the highest AUC of 0.866. Another significant finding was the substantial impact of sleep quality on the spontaneous clearance of HPV and regression of LSIL. CONCLUSIONS: In contrast to current cervical cancer prediction models, our model's prognostic capabilities extend to the spontaneous regression stage of cervical cancer. This model aids clinicians in real-time monitoring of lesions and in developing personalized treatment or follow-up plans by assessing individual risk factors, thus fostering lesion spontaneous reversal and aiding in cervical cancer prevention and reduction.


Asunto(s)
Lesiones Precancerosas , Medicina de Precisión , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Lesiones Precancerosas/patología , Lesiones Precancerosas/virología , Adulto , Aprendizaje Automático , Persona de Mediana Edad , Progresión de la Enfermedad , Modelos Biológicos
4.
Antioxidants (Basel) ; 13(7)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39061848

RESUMEN

Yeast culture (YC) plays a significant role in enhancing the performance and health of poultry breeding. This study investigated the impact of different YC supplementation concentrations (basal diet with 1.0 g/kg and 2.0 g/kg of YC, YC1.0, and YC2.0) on egg production performance, egg quality, antioxidant properties, intestinal mucosal structure, and intestinal flora of laying hens. Both YC1.0 and YC2.0 groups significantly enhanced the egg protein height, Haugh unit, and crude protein content of egg yolks compared to the control group (p < 0.05). The supplementation with YC2.0 notably increased the egg production rate, reduced feed-to-egg ratio, and decreased the broken egg rate compared to the control group (p < 0.05). Additionally, YC supplementation enhanced serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity while reducing malondialdehyde (MDA) content (p < 0.05). Moreover, YC supplementation promoted duodenal villus height and villus ratio in the duodenum and jejunum (p < 0.05). Analysis of cecal microorganisms indicated a decrease in Simpson and Shannon indices with YC supplementation (p < 0.05). YC1.0 reduced the abundance of Proteobacteria, while YC2.0 increased the abundance of Bacteroidales (p < 0.05). Overall, supplementation with YC improved egg production, quality, antioxidant capacity, intestinal morphology, and cecal microbial composition in laying hens, with significant benefits observed at the 2.0 g/kg supplementation level.

5.
Toxins (Basel) ; 16(7)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39057959

RESUMEN

Tenuazonic acid (TeA), usually found in cereals, fruits, vegetables, oil crops, and their products, was classified as one of the highest public health problems by EFSA as early as 2011, but it has still not been regulated by legislation due to the limited toxicological profile. Moreover, it has been reported that the coexistence of TeA and patulin (PAT) has been found in certain agricultural products; however, there are no available data about the combined toxicity. Considering that the gastrointestinal tract is the physiological barrier of the body, it would be the first target site at which exogenous substances interact with the body. Thus, we assessed the combined toxicity (cell viability, ROS, CAT, and ATP) in Caco-2 cells using mathematical modeling (Chou-Talalay) and explored mechanisms using non-targeted metabolomics and molecular biology methods. It revealed that the co-exposure of TeA + PAT (12.5 µg/mL + 0.5 µg/mL) can induce enhanced toxic effects and more severe oxidative stress. Mechanistically, the lipid and amino acid metabolisms and PI3K/AKT/FOXO signaling pathways were mainly involved in the TeA + PAT-induced synergistic toxic effects. Our study not only enriches the scientific basis for the development of regulatory policies but also provides potential targets and treatment options for alleviating toxicities.


Asunto(s)
Supervivencia Celular , Sinergismo Farmacológico , Metaboloma , Estrés Oxidativo , Patulina , Ácido Tenuazónico , Células CACO-2 , Patulina/toxicidad , Humanos , Ácido Tenuazónico/toxicidad , Ácido Tenuazónico/metabolismo , Metaboloma/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
6.
Mol Pharm ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049481

RESUMEN

Pancreatic cancer remains a formidable challenge in oncology due to its aggressive nature and limited treatment options. The dense stroma surrounding pancreatic tumors not only provides structural support but also presents a formidable barrier to effective therapy, hindering drug penetration and immune cell infiltration. This review delves into the intricate interplay between stromal components and cancer cells, highlighting their impact on treatment resistance and prognosis. Strategies for stromal remodeling, including modulation of cancer-associated fibroblasts (CAFs), pancreatic stellate cells (PSCs) activation states, and targeting extracellular matrix (ECM) components, are examined for their potential to enhance drug penetration and improve therapeutic efficacy. Integration of stromal remodeling with conventional therapies, such as chemotherapy and immunotherapy, is discussed along with the emerging field of intelligent nanosystems for targeted drug delivery. This comprehensive overview underscores the importance of stromal remodeling in pancreatic cancer treatment and offers insights into promising avenues for future research and clinical translation.

7.
J Agric Food Chem ; 72(26): 14557-14569, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38957088

RESUMEN

This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, withCurvularia lunata D43 being the most effective. Under salt stress, C. lunata D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.


Asunto(s)
Endófitos , Glycyrrhiza , Ácido Glicirrínico , Estrés Salino , Ácido Glicirrínico/metabolismo , Glycyrrhiza/química , Glycyrrhiza/metabolismo , Glycyrrhiza/microbiología , Endófitos/metabolismo , Endófitos/genética , Tolerancia a la Sal , Ascomicetos/metabolismo , Ascomicetos/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas
8.
BMC Microbiol ; 24(1): 240, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961341

RESUMEN

OBJECTIVE: We explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks. METHODS: 932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and blaKPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems. RESULTS: We found a significant inverse correlation between the presence of CRISPR and R-M systems and blaKPC plasmids in K. pneumoniae, especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in blaKPC-IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder blaKPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of blaKPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity. CONCLUSIONS: Our results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP.


Asunto(s)
Sistemas CRISPR-Cas , Conjugación Genética , Klebsiella pneumoniae , Plásmidos , Klebsiella pneumoniae/genética , Plásmidos/genética , beta-Lactamasas/genética , Enzimas de Restricción-Modificación del ADN/genética , China , Infecciones por Klebsiella/microbiología , Transferencia de Gen Horizontal , Humanos , Genoma Bacteriano/genética
9.
Mol Diagn Ther ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967864

RESUMEN

BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients. OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC. PATIENTS AND METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed. RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV. CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.

10.
Shanghai Kou Qiang Yi Xue ; 33(2): 186-189, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-39005097

RESUMEN

PURPOSE: To investigate the effects of chronic periodontitis on the quality of life and severity of the disease in patients with bronchiectasis. METHODS: A total of 80 bronchiectasis patients admitted to The Fourth Hospital of Changsha between April 2021 and April 2023 were randomly selected. Patients were divided into two groups according to whether they had moderate to severe chronic periodontitis: bronchiectasis with periodontitis group (n=45) and bronchiectasis without periodontitis group (n=35). The Qualify of Life Questionnaire for Bronchiectasi(QoL-B) was used to assess patients' quality. The severity of the disease was assessed using the Bronchiectasis Severity Index (BSI), and serum levels of hypersensitive C-reactive protein (hsCRP), tumor necrosis factor alpha(TNF-alpha), and interleukin-6(IL-6) were detected. SPSS 20.0 software package was used for data analysis. RESULTS: The QoL-B score of bronchiectasis with periodontitis group was significantly lower than that of bronchiectasis without periodontitis group, and the BSI score was significantly higher than that of bronchiectasis without periodontitis group(P<0.05). The levels of hs-CRP, TNF-alpha and IL-6 in bronchiectasis with periodontitis were significantly higher than those in bronchiectasis without periodontitis group(P<0.05). CONCLUSIONS: Chronic periodontitis shows significant adverse effects on both quality of life and disease severity in patients with bronchiectasis, which may be related to the common mechanism of inflammatory response between the two kinds of diseases.


Asunto(s)
Bronquiectasia , Proteína C-Reactiva , Periodontitis Crónica , Interleucina-6 , Calidad de Vida , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa , Humanos , Bronquiectasia/psicología , Periodontitis Crónica/psicología , Periodontitis Crónica/sangre , Interleucina-6/sangre , Proteína C-Reactiva/análisis , Factor de Necrosis Tumoral alfa/sangre , Encuestas y Cuestionarios , Masculino , Femenino
11.
Zhongguo Zhen Jiu ; 44(7): 838-44, 2024 Jul 12.
Artículo en Chino | MEDLINE | ID: mdl-38986598

RESUMEN

This article summarizes and discusses the collaborative effects of acupuncture and medication in treatment, including four aspects, named "acupuncture synergizing the effects of medication", "medication advancing the effects of acupuncture", "coordination of acupuncture and medication", and "antagonism of acupuncture and medication". Regarding "acupuncture synergizing the effects of medication", the actions of acupuncture are predominant, which affects the absorption and metabolism of drugs in the body, increases drug concentration in blood, enhances the targeting effect of drugs, guides meridian tropism, alleviates the drug dose and adverse reactions, avoids the first pass effect and accelerates the drug bioavailability. As for "medication advancing the effects of acupuncture", the synergistic effect of acupuncture is obtained by medication, besides, the medication itself may supplement the drug property to the needles during acupuncture pretreatment so as to increase the therapeutic effect. In terms of "coordination of acupuncture and medication", and "antagonism of acupuncture and medication", there are the underlying co-effects of acupuncture and medication in the body, and the action targets may be same or different between them, thus, it needs to be further explored.


Asunto(s)
Terapia por Acupuntura , Humanos , Terapia Combinada
12.
J Adv Nurs ; 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39003640

RESUMEN

BACKGROUND: In the nursing profession, the concept of self-compassion has been associated with burnout. However, to date, the fine-grained relationships between different dimensions of self-compassion and symptoms of burnout have not been investigated. Network analysis provides a new avenue for exploring the fine-grained correlation paths of two related variables. AIM: To analyse the nuanced associations between self-compassion and burnout using network analysis in a large cohort of Chinese nurses. DESIGN: A cross-sectional multi-centre survey design study. METHODS: Participants were recruited from 30 hospitals in China between April and May 2022. These nurses completed the Chinese Maslach Burnout Inventory-General Survey (C-MBI-GS) and Self-Compassion Scale-Short Form (SCS-SF). Network analysis was performed to illustrate the complex nuanced relationships between self-compassion and burnout. RESULTS: A total of 1467 nurses (age 32.2 [18-56] years; 89.9% were female) participated in the study. Nodes Mindfulness and Isolation had the highest centralities measured by strength. Nodes Mindfulness, reduced personal accomplishment and Isolation were the most negative and positive influential nodes that bridged self-compassion and burnout. There were no differences in terms of gender, age, professional title and job tenure in the structure or connectivity of the self-compassion and burnout network. CONCLUSION: Different components of self-compassion were specifically associated with different dimensions of burnout in registered nurses. Among these, Mindfulness, Isolation and Reduced personal accomplishment were the three most important components of self-compassion for burnout symptoms. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT: Understanding the intricate connections between self-compassion and burnout will allow hospital administrators to prioritize the elements of Mindfulness and Isolation within self-compassion and the dimension of Reduced personal accomplishment within burnout when designing preventative measures and interventions aimed at reducing nurse burnout.

13.
Chem Sci ; 15(27): 10264-10280, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38994399

RESUMEN

Metals are essential for human health and play a crucial role in numerous biological processes and pathways. Gaining a deeper insight into these biological events will facilitate novel strategies for disease prevention, early detection, and personalized treatment. In recent years, there has been significant progress in the development of metal-detection based techniques from single cell metallome and proteome profiling to multiplex imaging, which greatly enhance our comprehension of the intricate roles played by metals in complex biological systems. This perspective summarizes the recent progress in advanced metal-detection based techniques and highlights successful applications in elucidating the roles of metals in biology and medicine. Technologies including machine learning that couple with single-cell analysis such as mass cytometry and their application in metallobiology, cancer biology and immunology are also emphasized. Finally, we provide insights into future prospects and challenges involved in metal-detection based techniques, with the aim of inspiring further methodological advancements and applications that are accessible to chemists, biologists, and clinicians.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38972753

RESUMEN

PURPOSE: This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD). METHODS: We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library, with the primary outcomes being overall survival (OS), acute cellular rejection (ACR), primary graft dysfunction (PGD), and length of stay (LOS). RESULTS: Five cohort studies were included in this meta-analysis, with 183 patients enrolled in the AE-ILD group and 337 patients in the stable-ILD group. The results showed that in regard to perioperative outcomes, the AE-ILD group did not differ from the stable-ILD group in the incidence of ACR (relative risks [RR] = 0.34, p = 0.44) and the incidence of PGD Ⅲ (RR = 0.53, p = 0.43), but had a longer LOS (mean difference = 9.15, p = 0.02). Regarding prognosis, the two also did not differ in 90-day OS (RR = 0.97, p = 0.59), 1-year OS (RR = 1.05, p = 0.66), and 3-year OS (RR = 0.91, p = 0.76). CONCLUSION: Our study concluded that the efficacy of lung transplantation in patients with AE-ILD is not inferior to that of patients with stable ILD. Lung transplantation is one of the potential treatments for patients with AE-ILD.


Asunto(s)
Progresión de la Enfermedad , Rechazo de Injerto , Tiempo de Internación , Enfermedades Pulmonares Intersticiales , Trasplante de Pulmón , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rechazo de Injerto/mortalidad , Rechazo de Injerto/diagnóstico , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/cirugía , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/fisiopatología , Trasplante de Pulmón/mortalidad , Trasplante de Pulmón/efectos adversos , Disfunción Primaria del Injerto/mortalidad , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/fisiopatología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
15.
Chem Sci ; 15(26): 10065-10072, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38966375

RESUMEN

The COVID-19 pandemic caused by SARS-CoV-2 resulted in a global public health crisis. In addition to vaccines, the development of effective therapy is highly desirable. Targeting a protein that plays a critical role in virus replication may allow pan-spectrum antiviral drugs to be developed. Among SARS-CoV-2 proteins, helicase (i.e., non-structural protein 13) is considered as a promising antiviral drug target due to its highly conserved sequence, unique structure and function. Herein, we demonstrate SARS-CoV-2 helicase as a target of bismuth-based antivirals in virus-infected mammalian cells by a metal-tagged antibody approach. To search for more potent bismuth-based antivirals, we further screened a panel of bismuth compounds towards inhibition of ATPase and DNA unwinding activity of nsp13 and identified a highly potent bismuth compound Bi(5-aminotropolonate)3, namely Bi(Tro-NH2)3 with an IC50 of 30 nM for ATPase. We show that bismuth-based compounds inhibited nsp13 unwinding activity via disrupting the binding of ATP and the DNA substrate to viral helicase. Binding of Bi(iii) to nsp13 also abolished the interaction between nsp12 and nsp13 as evidenced by immunofluorescence and co-immunoprecipitation assays. Finally, we validate our in vitro data in SARS-CoV-2 infected mammalian cells. Notably, Bi(6-TG)3 exhibited an EC50 of 1.18 ± 0.09 µM with a selective index of 847 in VeroE6-TMPRSS2 infected cells. This study highlights the important role of helicase for the development of more effective antiviral drugs to combat SARS-CoV-2 infection.

16.
Angew Chem Int Ed Engl ; : e202408379, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970405

RESUMEN

Formamide (HCONH2) plays a pivotal role in the manufacture of a diverse array of chemicals, fertilizers, and pharmaceuticals. Photocatalysis holds great promise for green fabrication of carbon-nitrogen (C-N) compounds owing to its environmental friendliness and mild redox capability. However, the selective formation of the C-N bond presents a significant challenge in the photocatalytic synthesis of C-N compounds. This work developed a photocatalytic radical coupling method for the formamide synthesis from co-oxidation of ammonia (NH3) and methanol (CH3OH). An exceptional formamide yield rate of 5.47 ± 0.03 mmol·gcat-1·h-1 (911.87 ± 0.05 mmol·gBi-1·h-1) was achieved over atomically dispersed Bi sites (BiSAs) on TiO2. An accumulation of 45.0 mmol·gcat-1 (0.2 g·gcat-1) of formamide was achieved after long-term illumination, representing the highest level of photocatalytic C-N compounds synthesis. The critical C-N coupling for formamide formation originated from the "σ-σ" interaction between electrophilic ●CH2OH with nucleophilic ●NH2 radical. The  BiSAs sites facilitated the electron transfer between reactants and photocatalysts and enhanced the nucleophilic attack of â—NH2 radical at the â—CH2OH radical, thereby advancing the selective C-N bond formation. This work deepens the understanding of the C-N coupling mechanism and offers an alternative and intriguing photocatalytic approach for the efficient and sustainable production of C-N compounds.

17.
Allergol Immunopathol (Madr) ; 52(4): 60-67, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38970266

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a familiar disease, and owns high morbidity and mortality, which critically damages the health of patients. Ubiquitin-specific peptidase 8 (USP8) is a pivotal protein to join in the regulation of some diseases. In a previous report, it was determined that USP8 expression is down-regulated in LPS-treated BEAS-2B cells, and USP8 restrains inflammatory response and accelerates cell viability. However, the regulatory roles of USP8 on ferroptosis in COPD are rarely reported, and the associated molecular mechanisms keep vague. OBJECTIVE: To investigate the regulatory functions of USP8 in COPD progression. MATERIAL AND METHODS: The lung functions were measured through the Buxco Fine Pointe Series Whole Body Plethysmography (WBP). The Fe level was tested through the Fe assay kit. The protein expressions were assessed through western blot. The levels of tumor necrosis -factor-α, interleukin 6, and interleukin 8 were evaluated through enzyme-linked immunosorbent serologic assay. Cell viability was tested through CCK-8 assay. RESULTS: In this work, it was discovered that overexpression of USP8 improved lung function in COPD mice. In addition, overexpression of USP8 repressed ferroptosis by regulating glutathione peroxidase 4 and acyl-CoA synthetase long-chain family 4 expressions in COPD mice. Overexpression of USP8 suppressed inflammation in COPD mice. Furthermore, overexpression of USP8 suppressed ferroptosis in COPD cell model. At last, it was verified that overexpression of USP8 accelerated ubiquitin aldehyde-binding protein 1 (OTUB1)/solute carrier family 7 member 11 (SLC7A11) pathway. CONCLUSION: This study manifested that overexpression of USP8 restrained inflammation and ferroptosis in COPD by regulating the OTUB1/SLC7A11 signaling pathway. This discovery hinted that USP8 could be a potential target for COPD treatment.


Asunto(s)
Sistema de Transporte de Aminoácidos y+ , Ferroptosis , Enfermedad Pulmonar Obstructiva Crónica , Transducción de Señal , Ubiquitina Tiolesterasa , Ferroptosis/fisiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Animales , Humanos , Ratones , Transducción de Señal/inmunología , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Masculino , Inflamación/metabolismo , Inflamación/inmunología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Línea Celular , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/genética , Endopeptidasas
18.
Ecotoxicol Environ Saf ; 282: 116702, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39018732

RESUMEN

Polluted environments often contain large amounts of toxic metals, such as cadmium, which pose a major threat to ecosystems and public health. Contamination by cadmium and its compounds is often observed in areas surrounding zinc mining sites and electroplating factories, and the control of cadmium pollution is essential for environmental safety and health. In this study, a highly efficient and straightforward separation strategy for K4Fe(CN)6@Fe3O4 nanocomposites is successfully developed to capture the Cd ions in the water environment. Batch adsorption experiments revealed that K4Fe(CN)6@Fe3O4 exhibited a high cadmium removal rate (greater than 98 %) at a pH level of 6.0 and solid-liquid ratio of 1.0 g/L at room temperature (298 K). Kinetic analysis revealed that the adsorption process followed a pseudo-second-order model and cadmium was rapidly removed in the first 10 min, with chemisorption dominating the capture of Cd2+ by K4Fe(CN)6@Fe3O4. Adsorption isotherms revealed a heterogeneous adsorption behavior, with a maximum adsorption capacity of 40.78 mg/g. The intrinsic adsorption of Cd2+ by K4Fe(CN)6@Fe3O4 occurring primarily through electrostatic interaction and ion exchange. In addition, K4Fe(CN)6@Fe3O4 exhibited an excellent regeneration capacity. Therefore, integrating Fe3O4 into the metal cyanide not only provided the composite material with excellent chemical stability and selective adsorption sites for Cd2+, but also facilitated subsequent sorbent collection and recovery. Overall, this study presents a simple and feasible approach for integrating Fe3O4 into potassium ferrocyanide frameworks for efficient cadmium removal from contaminated water.

19.
Huan Jing Ke Xue ; 45(7): 3953-3964, 2024 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-39022943

RESUMEN

In order to explore the spatiotemporal variation characteristics and driving mechanism of water quality in the Xiangjiang River Basin, the data of 16 water quality parameters at 113 stations over 26 years from 1990 to 2016 in the Xiangjiang River Basin were collected for synthetically assessing the water quality and identifying its main pollutants through the water quality index and other methods. The causal mechanism of water quality, especially the driving effect of water level and land use pattern, was analyzed. The results showed that: ① The overall water quality grade of the Xiangjiang River Basin during the study period was "good." However, the water quality deteriorated first (from 1990 to 2003) and then improved (from 2004 to 2016). The season variation in water quality was not obvious, but the water quality fluctuation of the wet season was larger. The water pollution load of the main stream decreased successively from the middle reaches, downstream reaches, and upstream reaches. The upstream tributaries had the best water quality, whereas areas with poor water quality were mainly distributed at the mouth of the middle and downstream tributaries, especially in areas where multiple tributaries converged. ② Toxic heavy metals had the characteristics of toxicity, persistence, and bioaccumulation. If they exceeded a certain concentration in water, they were difficult to purify, posing great harm to the natural environment and human health. The toxic metal index (CI1) was the leading factor affecting water quality, in which Hg and Cd were the main parameters affecting the overall water quality of the Xiangjiang River Basin. ③ The water level had a positive impact on the water quality of the Xiangjiang River by diluting environmental parameters. Land type had little effect on heavy metal concentration, whereas forest land could improve water quality. Grassland had a negative correlation with permanganate index over a large scale range (≥ 5 km). The increase in water bodies, arable land, and impermeable surface areas within the watershed increased the probability of high fecal coliform concentration in the water body. ④ With the increase in buffer distance, the water quality explained by the land use pattern increased. On the scale of 10 km buffer zone in the riparian zone, the explanation degree by land use pattern on water quality was the highest, which was an effective scale for water quality control of the Xiangjiang River. This research showed that the driving factors of heavy metal pollution and other pollution were different, but their regional differences were all obvious in the Xiangjiang River Basin. Therefore, pollution control should be classified and taken according to local conditions.

20.
Biotechnol J ; 19(7): e2300653, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39014929

RESUMEN

Cervical cancer (CC) remains a major cause of cancer-related mortality among women globally. Long noncoding RNAs (lncRNAs) play crucial regulatory roles in various cancers, including CC. This study investigates the function of a novel lncRNA, USP30 antisense RNA 1 (USP30-AS1), in CC tumorigenesis. We analyzed USP30-AS1 expression using RT-qPCR and conducted in vitro loss-of-function assays, as well as in vivo assays, to evaluate the effects of USP30-AS1 silencing on CC cell growth and migration. Additional mechanistic experiments, including RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays, were performed to elucidate the regulatory mechanisms influenced by USP30-AS1. We discovered that USP30-AS1 is overexpressed in CC tissues and cells. Silencing USP30-AS1 significantly reduced cell proliferation, migration, invasion, and tumor growth. Moreover, USP30-AS1 was found to modulate the expression of ubiquitin-specific peptidase 30 (USP30) by sponging microRNA-2467-3p (miR-2467-3p) and recruiting the FUS RNA binding protein (FUS), thereby stabilizing ß-catenin and activating the Wnt/ß-catenin signaling pathway. These findings suggest that USP30-AS1 enhances CC cell growth and migration through the miR-2467-3p/FUS/USP30 axis, highlighting its potential as a biomarker for CC.


Asunto(s)
Proliferación Celular , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Vía de Señalización Wnt , beta Catenina , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Femenino , Vía de Señalización Wnt/genética , beta Catenina/metabolismo , beta Catenina/genética , Proliferación Celular/genética , Línea Celular Tumoral , Animales , Movimiento Celular/genética , Ratones , Regulación Neoplásica de la Expresión Génica/genética , Exosomas/metabolismo , Exosomas/genética , MicroARNs/genética , MicroARNs/metabolismo , Progresión de la Enfermedad , Ratones Desnudos
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