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1.
Acta Pharmacol Sin ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862818

RESUMEN

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

2.
Biomed Environ Sci ; 37(5): 503-510, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38843923

RESUMEN

Objective: VATER/VACTERL-like association is associated with adverse pregnancy outcomes. Genetic evidence of this disorder is sporadic. In this study, we aimed to provide genetic insights to improve the diagnosis of VACTERL. Methods: We have described a Chinese family in which four members were affected by renal defects or agenesis, anal atresia, and anovaginal fistula, which is consistent with the diagnosis of a VACTERL-like association. Pedigree and genetic analyses were conducted using genome and exome sequencing. Results: Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals, harboring a 196-380 kb microdeletion on Xq27.1, which was identified by familial exome sequencing. Genome sequencing was performed on the affected male, confirming a -196 kb microdeletion in Xq27.1, which included a 28% loss of the CDR-1 gene. Four family members were included in the co-segregation analysis, and only VACTERL-like cases with microdeletions were reported in X27.1. Conclusion: These results suggest that the 196-380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association. However, further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.


Asunto(s)
Canal Anal , Cromosomas Humanos X , Linaje , Adulto , Femenino , Humanos , Masculino , Canal Anal/anomalías , China , Deleción Cromosómica , Cromosomas Humanos X/genética , Pueblos del Este de Asia/genética , Esófago/anomalías , Cardiopatías Congénitas , Riñón/anomalías , Deformidades Congénitas de las Extremidades/genética , Columna Vertebral/anomalías , Tráquea/anomalías
3.
Tob Control ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844345

RESUMEN

BACKGROUND: Although Singapore has completely banned vaping, it is heavily promoted on social media. This study explored vaping-related social media content that Singaporeans are exposed to, and how it shapes vaping-related perceptions and experiences in the context of Singapore's strict regulations. METHODS: We held 10 focus group discussions with 63 Singaporeans aged 21-40 years, with diversity by sociodemographics, smoking history, vaping history and self-reported exposure to vaping-related social media content. Participants provided screenshots of any vaping-related content they encountered on their social media. Subsequently, in focus groups, they were shown a variety of this content and asked to discuss. We coded transcripts using inductive methods. RESULTS: Participants had encountered vape advertisements from neighbouring countries featuring attractive products, flavours, celebrity endorsements and entertainment shows, which they found highly appealing. Participants encountered posts that did not overtly advertise vaping but depicted people vaping in social settings, thereby normalising vaping despite its illegal status. They perceived government campaigns to deter vaping as biased and agenda driven, calling for a more nuanced message and use of local influencers and personal stories to communicate the rationale of the vaping regulations to the public. CONCLUSION: Having a law that bans vaping may not be enough; it needs to be complemented with more comprehensive marketing restrictions on social media platforms and effective enforcement of bans on social media promotions from overseas.

4.
Soft Matter ; 20(20): 4052-4056, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38738402

RESUMEN

Stimuli-responsive upconversion nanoparticle (UCNP)-poly-N-isopropylacrylamide (pNIPAM)/DNA core-shell microgels with tunable sizes and programmable functions have been prepared. Thanks to the near-infrared (NIR)-responsive UCNP cores and thermosensitive polymeric shells, functional DNA-incorporated microgels with high DNA activity and loading efficiency are obtained, and the activity of the loaded DNA structures can be smartly regulated by NIR illumination and temperature simultaneously.

5.
Innovation (Camb) ; 5(4): 100624, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38746910

RESUMEN

The broader application of lithium-ion batteries (LIBs) is constrained by safety concerns arising from thermal runaway (TR). Accurate prediction of TR is essential to comprehend its underlying mechanisms, expedite battery design, and enhance safety protocols, thereby significantly promoting the safer use of LIBs. The complex, nonlinear nature of LIB systems presents substantial challenges in TR modeling, stemming from the need to address multiscale simulations, multiphysics coupling, and computing efficiency issues. This paper provides an extensive review and outlook on TR modeling technologies, focusing on recent advances, current challenges, and potential future directions. We begin with an overview of the evolutionary processes and underlying mechanisms of TR from multiscale perspectives, laying the foundation for TR modeling. Following a comprehensive understanding of TR phenomena and mechanisms, we introduce a multiphysics coupling model framework to encapsulate these aspects. Within this framework, we detail four fundamental physics modeling approaches: thermal, electrical, mechanical, and fluid dynamic models, highlighting the primary challenges in developing and integrating these models. To address the intrinsic trade-off between computational accuracy and efficiency, we discuss several promising modeling strategies to accelerate TR simulations and explore the role of AI in advancing next-generation TR models. Last, we discuss challenges related to data availability, model scalability, and safety standards and regulations.

6.
Medicine (Baltimore) ; 103(20): e38235, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758857

RESUMEN

BACKGROUND: This randomized controlled trial aimed to evaluate the efficacy of preoperative inhaled budesonide combined with intravenous dexamethasone on postoperative sore throat (POST) after general anesthesia in patients who underwent thyroidectomy. METHODS: Patients who underwent elective thyroidectomy were randomly divided into the intravenous dexamethasone group (group A) and budesonide inhalation combined with intravenous dexamethasone group (group B). All patients underwent general anesthesia. The incidence and severity of POST, hoarseness, and cough at 1, 6, 12, and 24 hours after surgery were evaluated and compared between the 2 groups. RESULTS: There were 48 and 49 patients in groups A and B, respectively. The incidence of POST was significantly lower at 6, 12, and 24 hours in group B than that in group A (P < .05). In addition, group B had a significantly lower incidence of coughing at 24 hours (P = .047). Compared with group A, the severity of POST was significantly lower at 6 (P = .027), 12 (P = .004), and 24 (P = .005) hours at rest, and at 6 (P = .002), 12 (P = .038), and 24 (P = .015) hours during swallowing in group B. The incidence and severity of hoarseness were comparable at each time-point between the 2 groups (P > .05). CONCLUSION: Preoperative inhaled budesonide combined with intravenous dexamethasone reduced the incidence and severity of POST at 6, 12, and 24 hours after extubation compared with intravenous dexamethasone alone in patients who underwent thyroidectomy. Additionally, this combination decreased the incidence of postoperative coughing at 24 hours.


Asunto(s)
Budesonida , Dexametasona , Faringitis , Complicaciones Posoperatorias , Cuidados Preoperatorios , Tiroidectomía , Humanos , Masculino , Femenino , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Budesonida/administración & dosificación , Tiroidectomía/efectos adversos , Faringitis/prevención & control , Faringitis/etiología , Faringitis/epidemiología , Persona de Mediana Edad , Administración por Inhalación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Adulto , Cuidados Preoperatorios/métodos , Administración Intravenosa , Quimioterapia Combinada , Ronquera/prevención & control , Ronquera/etiología , Ronquera/epidemiología , Anestesia General/métodos , Anestesia General/efectos adversos , Glucocorticoides/administración & dosificación , Resultado del Tratamiento
7.
Front Endocrinol (Lausanne) ; 15: 1361447, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38812818

RESUMEN

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.


Asunto(s)
Índice de Masa Corporal , Factores de Riesgo Cardiometabólico , Capacidad Cardiovascular , Humanos , Masculino , Femenino , Niño , Capacidad Cardiovascular/fisiología , China/epidemiología , Adiposidad/fisiología , Obesidad Infantil/epidemiología , Obesidad Infantil/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Pueblos del Este de Asia
8.
J Microbiol Biotechnol ; 34(6): 1-10, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38755002

RESUMEN

This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxideGrapheneOxide/Chitosan/ß-Glycerophosphate (ZnO-GO/CS/ß-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/ß-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/ß-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/ß-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/ß-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

9.
Fitoterapia ; 176: 106007, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38744384

RESUMEN

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

10.
Taiwan J Obstet Gynecol ; 63(3): 307-311, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38802192

RESUMEN

Trace metals play a vital role in a variety of biological processes, but excessive amounts can be toxic and are receiving increasing attention. Trace metals in the environment are released from natural sources, such as rock weathering, volcanic eruptions, and other human activities, such as industrial emissions, mineral extraction, and vehicle exhaust. Lifestyle, dietary habits and environmental quality are the main sources of human exposure to trace metals, which play an important role in inducing human reproductive infertility. The purpose of this review is to summarize the distribution of various trace metals in oocyte and to identify the trace metals that may cause oocyte used in the design and execution of toxicological studies.


Asunto(s)
Oocitos , Oligoelementos , Humanos , Oocitos/efectos de los fármacos , Oligoelementos/análisis , Oligoelementos/efectos adversos , Femenino , Exposición a Riesgos Ambientales/efectos adversos , Metales Pesados/análisis , Metales/efectos adversos , Metales/análisis
11.
DNA Cell Biol ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700464

RESUMEN

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH), a type of overgrowth syndrome, is characterized by progressive megalencephaly, cortical brain malformations, and distal limb anomalies. Previous studies have revealed that the overactivity of the phosphatidylinositol 3-kinase-Protein kinase B pathway and the increased cyclin D2 (CCND2) expression were the main factors contributing to this disease. Here, we present the case of a patient who exhibited megalencephaly, polymicrogyria, abnormal neuronal migration, and developmental delay. Serum tandem mass spectrometry and chromosome examination did not detect any metabolic abnormalities or copy number variants. However, whole-exome sequencing and Sanger sequencing revealed a de novo nonsense mutation (NM_001759.3: c.829C>T; p.Gln277X) in the CCND2 gene of the patient. Bioinformatics analysis predicted that this mutation may disrupt the structure and surface charge of the CCND2 protein. This disruption could potentially prevent polyubiquitination of CCND2, leading to its resistance against degradation. Consequently, this could drive cell division and growth by altering the activity of key cell cycle regulatory nodes, ultimately contributing to the development of MPPH. This study not only presents a new case of MPPH and expands the mutation spectrum of CCND2 but also enhances our understanding of the mechanisms connecting CCND2 with overgrowth syndromes.

12.
Infect Agent Cancer ; 19(1): 21, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693556

RESUMEN

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

13.
Anal Chem ; 96(23): 9379-9389, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38805056

RESUMEN

Over the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.


Asunto(s)
Cromatografía de Gases y Espectrometría de Masas , Metabolómica , Cromatografía de Gases y Espectrometría de Masas/métodos , Metabolómica/métodos , Animales , Factores de Tiempo , Análisis de Datos
14.
Sci Total Environ ; 927: 172338, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608897

RESUMEN

Algal blooms in lakes have been a challenging environmental issue globally under the dual influence of human activity and climate change. Considerable progress has been made in the study of phytoplankton dynamics in lakes; The long-term in situ evolution of dominant bloom-forming cyanobacteria in meso-eutrophic plateau lakes, however, lacks systematic research. Here, the monthly parameters from 12 sampling sites during the period of 1997-2022 were utilized to investigate the underlying mechanisms driving the superiority of bloom-forming cyanobacteria in Erhai, a representative meso-eutrophic plateau lake. The findings indicate that global warming will intensify the risk of cynaobacteria blooms, prolong Microcystis blooms in autumn to winter or even into the following year, and increase the superiority of filamentous Planktothrix and Cylindrospermum in summer and autumn. High RUETN (1.52 Biomass/TN, 0.95-3.04 times higher than other species) under N limitation (TN < 0.5 mg/L, TN/TP < 22.6) in the meso-eutrophic Lake Erhai facilitates the superiority of Dolichospermum. High RUETP (43.8 Biomass/TP, 2.1-10.2 times higher than others) in TP of 0.03-0.05 mg/L promotes the superiority of Planktothrix and Cylindrospermum. We provided a novel insight into the formation of Planktothrix and Cylindrospermum superiority in meso-eutrophic plateau lake with low TP (0.005-0.07 mg/L), which is mainly influenced by warming, high RUETP and their vertical migration characteristics. Therefore, we posit that although the obvious improvement of lake water quality is not directly proportional to the control efficacy of cyanobacterial blooms, the evolutionary shift in cyanobacteria population structure from Microcystis, which thrives under high nitrogen and phosphorus conditions, to filamentous cyanobacteria adapted to low nitrogen and phosphorus levels may serve as a significant indicator of water quality amelioration. Therefore, we suggest that the risk of filamentous cyanobacteria blooms in the meso-eutrophic plateau lake should be given attention, particularly in light of improving water quality and global warming, to ensure drinking water safety.


Asunto(s)
Cianobacterias , Eutrofización , Lagos , Temperatura , Lagos/microbiología , Lagos/química , China , Monitoreo del Ambiente , Nitrógeno/análisis , Fitoplancton , Cambio Climático , Estaciones del Año , Fósforo/análisis , Nutrientes/análisis , Calentamiento Global
15.
Biochem Biophys Res Commun ; 715: 149999, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38678787

RESUMEN

Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition and metabolic disorder, has emerged as a significant health issue worldwide. D-mannose, a natural monosaccharide widely existing in plants and animals, has demonstrated metabolic regulatory properties. However, the effect and mechanism by which D-mannose may counteract NAFLD have not been studied. In this study, network pharmacology followed by molecular docking analysis was utilized to identify potential targets of mannose against NAFLD, and the leptin receptor-deficient, genetically obese db/db mice was employed as an animal model of NAFLD to validate the regulation of D-mannose on core targets. As a result, 67 targets of mannose are predicted associated with NAFLD, which are surprisingly centered on the mechanistic target of rapamycin (mTOR). Further analyses suggest that mTOR signaling is functionally enriched in potential targets of mannose treating NAFLD, and that mannose putatively binds to mTOR as a core mechanism. Expectedly, repeated oral gavage of supraphysiological D-mannose ameliorates liver steatosis of db/db mice, which is based on suppression of hepatic mTOR signaling. Moreover, daily D-mannose administration reduced hepatic expression of lipogenic regulatory genes in counteracting NAFLD. Together, these findings reveal D-mannose as an effective and potential NAFLD therapeutic through mTOR suppression, which holds translational promise.


Asunto(s)
Manosa , Farmacología en Red , Enfermedad del Hígado Graso no Alcohólico , Serina-Treonina Quinasas TOR , Animales , Manosa/farmacología , Manosa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Ratones , Masculino , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos
17.
Artículo en Inglés | MEDLINE | ID: mdl-38639616

RESUMEN

Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

18.
Heliyon ; 10(7): e28959, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38601542

RESUMEN

Stroke represents a significant threat to global human health, characterized by high rates of morbidity, disability, and mortality. Predominantly, strokes are ischemic in nature. Ischemic stroke (IS) is influenced by various cell death pathways, notably autophagy and ferroptosis. Recent studies have increasingly highlighted the interplay between autophagy and ferroptosis, a process likely driven by the accumulation of reactive oxygen species (ROS). Post-IS, either the inhibition of autophagy or its excessive activation can escalate ROS levels. Concurrently, the interaction between ROS and lipids during ferroptosis further augments ROS accumulation. Elevated ROS levels can provoke endoplasmic reticulum stress-induced autophagy and, in conjunction with free iron (Fe2+), can trigger ferroptosis. Moreover, ROS contribute to protein and lipid oxidation, endothelial dysfunction, and an inflammatory response, all of which mediate secondary brain injury following IS. This review succinctly explores the mechanisms of ROS-mediated crosstalk between autophagy and ferroptosis and the detrimental impact of increased ROS on IS. It also offers novel perspectives for IS treatment strategies.

19.
RSC Med Chem ; 15(4): 1198-1209, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38665835

RESUMEN

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

20.
BMC Genomics ; 25(1): 354, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594645

RESUMEN

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.


Asunto(s)
Actinidia , Proteínas de Homeodominio , Proteínas de Homeodominio/genética , Genoma de Planta , Filogenia , Actinidia/genética , Leucina Zippers/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Perfilación de la Expresión Génica
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