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1.
Transl Lung Cancer Res ; 13(9): 2254-2268, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39430316

RESUMEN

Background: The prognostic predictors of the synchronous multiple primary lung cancer (SMPLC) still remain unclear, and there is a lack of studies on the prognosis of SMPLC patients excluding those with multifocal ground-glass/lepidic (GG/L) nodules. The aim of this study is to develop an effective model for predicting survival of SMPLC patients. Methods: In this multicenter cohort study, a total of 831 SMPLC patients presenting for lung cancer resection from January 2004 to January 2018 at five institutions were included for developing and validating a nomogram model. Specifically, 499 patients from the Cancer Hospital, Chinese Academy of Medical Sciences, and Beijing Chao-Yang Hospital, Capital Medical University were served as the training cohort. A total of 332 patients from The Third Xiangya Hospital of Central South University, the First Affiliated Hospital of University of Science and Technology of China, and Beijing Liangxiang Hospital were served as the external validation cohort. The nomogram model was compared with the Tumor Node Metastasis (TNM) system for the overall survival. The C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the model performance. A user-friendly website for SMPLC survival probability calculation was also provided for a better understanding of prognosis of patients with resected SMPLC. Results: A total of seven independent risk factors were selected by conducting a multivariate analysis on the training set. Further, a nomogram model was developed with these factors. Both the internal and external validations exhibited good discrimination (C-index: internal, 0.827; external, 0.784). The NRI and IDI of this model were 0.33 and 0.21, respectively. The survival rates for 1-year, 3-year, and 5-year were consistent with the actual observed values. A set of cutoff values were determined by grouping the patients into three different groups. For each group, we should expect a significant distinction between survival curves. Conclusions: The novel nomogram model enables accurate survival risk stratification of patients with resected SMPLC and may assist in decision-making that is conducive to patients with SMPLC at high risk.

2.
Echocardiography ; 41(10): e15944, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39387115

RESUMEN

BACKGROUND: Gestational diabetes mellitus (GDM) poses a risk for cardiovascular damage during pregnancy. This study focused on evaluating changes in left ventricular myocardial performance in GDM patients using the left ventricular pressure-strain loop (LV-PSL) method and examining risk factors associated with reduced myocardial function. METHODS: A prospective, randomized study involving 112 pregnant women diagnosed with GDM was conducted from June 2021 to June 2024. Additionally, 84 healthy pregnant women from the same period served as the control group. Utilizing both conventional echocardiography and two-dimensional speckle tracking echocardiography, left ventricular myocardial work metrics were assessed using LV-PSL technology. RESULTS: GDM patients demonstrated significantly reduced values for global longitudinal strain (GLS), global work index (GWI), global work efficiency (GWE), and global constructive work (GCW) (p < 0.05), while conventional ultrasound measures showed no significant difference between GDM and control groups. GWI, GWE, GCW, and GLS had high predictive value for cardiac function changes in GDM patients, with GWE showing the highest predictive value {Area under curve (AUC) = 0.866, cutoff value = 95.5%, specificity = 0.77, sensitivity = 0.87}. GWI, GWE, and GCW were negatively correlated with GLS (r = -0.532, -0.411, -0.425, all p < 0.001), whereas global wasted work (GWW) showed a positive correlation with GLS (r = 0.325 and p < 0.001). These parameters were also correlated with HbA1c levels (r = -0.316, -0.256, -0.260, all p < 0.001 for negative correlations, and r = 0.172, p < 0.05 for positive correlations). Multivariate logistic regression indicated that 1-h OGTT (mmol/L), 2-h OGTT (mmol/L), and HbA1c (%) were significant predictors of left ventricular systolic function (GWE) in GDM patients. CONCLUSIONS: LV-PSL is an effective tool for early detection of left ventricular systolic function impairment in GDM patients.


Asunto(s)
Diabetes Gestacional , Ecocardiografía , Ventrículos Cardíacos , Humanos , Diabetes Gestacional/fisiopatología , Femenino , Embarazo , Adulto , Estudios Prospectivos , Ecocardiografía/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Función Ventricular Izquierda/fisiología , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Presión Ventricular/fisiología
3.
Front Microbiol ; 15: 1444235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39386365

RESUMEN

In this study, a ddPCR method for the detection of scale drop disease virus (SDDV) in yellowfin seabream (Acanthopagrus latus) was established based on Real-time fluorescence quantitative PCR detection methods and principles. The reaction conditions were optimized, and the sensitivity, specificity, accuracy, and reproducibility were assessed. The results showed that threshold line position was determined to be 1900 by the ddPCR method; the optimum annealing temperature for SDDV detection by the ddPCR method was 60°C; the limit of detection was 1.4-1.7 copies/µL; the results of specific detection of other common viruses, except for SDDV specific amplification, were all negative; and the relative standard deviation (RSD) for the reproducibility validation was 0.77%. The samples of yellowfin seabream (Acanthopagrus latus) liver, spleen, kidney, heart, intestine, brain, blood, muscle, skin and ascites with three replicates, respectively, were tested using the ddPCR method, and the results were consistent with clinical findings. The ddPCR method established in this study has the advantages of high sensitivity, high specificity, good reproducibility and simple steps for the quantitative detection of SDDV, which could be used for the nucleic acid detection of clinical SDDV samples, and provided a new quantitative method for the diagnosis of yellowfin seabream SDDV in the early stage of pathogenesis.

5.
J Am Coll Cardiol ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39387764

RESUMEN

BACKGROUND: Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) have been used to reduce the level of low-density lipoprotein cholesterol (LDL-C), but require either biweekly or monthly dosing frequency. Recaticimab is a new humanized monoclonal antibody selectively targeting PCSK9, with long-acting characteristic. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of recaticimab monotherapy in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk, and to explore different dosing strategies to provide patients with flexible administration options. METHODS: This was a randomized, double-blind, placebo-controlled, phase 3 study conducted at 59 sites in China. Patients with fasting LDL-C ≥2.6 to <4.9 mmol/L, fasting triglyceride ≤5.6 mmol/L, and 10-year ASCVD risk score <10% were randomly assigned (2:2:2:1:1:1) to receive subcutaneous injections of recaticimab at 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg every 12 weeks (Q12W), or matching placebo, on background lipid-lowering diet. Primary endpoint was percentage change in LDL-C from baseline to week 12 for 150 mg Q4W and 450 mg Q12W and to week 16 for 300 mg Q8W. RESULTS: A total of 703 patients underwent randomization and received recaticimab (n = 157, 156, and 155 for 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W, respectively) or placebo (n = 78, 79, and 78, respectively). Compared with placebo, recaticimab further reduced LDL-C by 49.6% (95% CI: 44.2%-54.9%) at 150 mg Q4W, 52.8% (95% CI: 48.3%-57.2%) at 300 mg Q8W, and 45.0% (95% CI: 41.0%-49.0%) at 450 mg Q12W (P < 0.0001 for all comparisons). Safety with recaticimab was comparable to placebo. After 12 or 16 weeks of treatment, patients who received recaticimab continued treatment until week 24, whereas those allocated to placebo were switched to recaticimab treatment with the same dosing strategy. Both 24-week recaticimab and 12- or 8-week recaticimab switched from placebo were effective. With 24 weeks of recaticimab treatment, the most common treatment-related adverse event was injection site reaction (n = 23 [4.9%]). CONCLUSIONS: Recaticimab monotherapy yielded significant LDL-C reductions and showed comparable safety vs placebo in patients with nonfamilial hypercholesterolemia and mixed hyperlipemia at low-to-moderate ASCVD risk, even with an infrequent dosing interval up to Q12W.

6.
Eur J Prev Cardiol ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39400052

RESUMEN

BACKGROUND: Although prior observational studies have suggested that patients with non-alcohol fatty liver disease (NAFLD) may have a higher risk of coronary artery calcification (CAC), these findings remain controversial. This study aimed to explore the causal association between NAFLD and CAC at genetic level by two-sample Mendelian randomization (MR) analysis. METHOD: Utilizing summary-level data from multiple large-scale genome-wide association studies (GWAS) in European populations, a two-sample MR analysis was initially conducted to explore the potential causal association between NAFLD and CAC. The results of the MR analysis were pooled through random-effect meta-analysis. The inverse variance weighting (IVW) method served as the primary approach for MR analysis. Additionally, the weighted median, MR-Egger and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods was applied for sensitivity analysis. Summary-level data on liver fatty content was utilized for validation analysis, while summary-level data on cirrhosis served as positive control, further ensuring the validity and robustness of our findings. Reverse MR analysis was performed to assess the association between CAC and NAFLD, employing instrument variables derived from CAC. RESULTS: The MR analysis indicated that genetically predicted NAFLD had no effects on the risk of CAC (Beta: 0.01, 95% CI: -0.02 to 0.03, P = 0.74). Likewise, the reverse MR analysis found no significant genetic association between CAC and NAFLD (OR: 1.00, 95% CI: 0.96 to 1.06, P = 0.88). Validation analysis yielded consistent results, showing no significant association between fatty liver content and CAC. CONCLUSION: Our two-sample MR analysis did not support that there is a causal association between NAFLD and CAC at genetic level. The association between NAFLD and CAC reported in some previous observational studies may rely on NAFLD complicated with metabolic disorders, rather than being directly linked to the hepatic steatosis.


This study used a genetic approach to investigate whether non-alcoholic fatty liver disease (NAFLD) directly causes coronary artery calcification (CAC), finding no evidence of a causal relationship at genetic level. The Mendelian randomization (MR) analysis revealed no genetic association between NAFLD and the risk of developing CAC, as well as no reverse association from CAC to NAFLD. The findings suggest that previous reports association between NAFLD and CAC may be influenced by metabolic disorders rather than a direct connection between the two conditions.

7.
Schizophr Bull ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39406395

RESUMEN

BACKGROUND AND HYPOTHESIS: Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. STUDY DESIGN: We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. STUDY RESULTS: The FES group showed higher serum NMDAR Ab levels [(9.23 ±â€…4.15) ng/mL vs. (7.08 ±â€…2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). CONCLUSIONS: Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

9.
Adv Mater ; : e2410676, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39402913

RESUMEN

Chiral inorganic nanomaterials (CINMs) have garnered significant interest due to their exceptional optical, electronic, and catalytic properties, offering promising advancements in energy conversion, data storage, catalysis, and biomedicine. While traditional optical spectrophotometers reveal the chiroptical performance of CINMs on an ensemble level, the direct structural visualization for the qualitative and quantitative discernment of their chiral features has become increasingly distinct with the advancements of transmission electron microscopy (TEM) techniques. The need for reasonable and high-standard discrimination requirements of CINMs has driven the progress of chirality-based TEM technologies. Therefore, this review in the good season takes the initiative to summarize the current advancements in TEM technologies for CINMs characterization, emphasizing a qualitative analysis of chiral atomic-level features, 0D, 1D, and 2D nanocrystals, and assembled nanomaterials. Then, the quantitative methods for determining chirality is also highlighted, such as 3D electron tomography, and further address the evolution of chiral structures monitored by the Ex-situ and In-situ TEM technologies. By providing a roadmap for the current challenges and proposing future advancements in TEM technologies for the qualitative, quantitative, and real-time analysis of CINMs, it can drive innovations in the field of chiral nanomaterials as well as the development of TEM technologies.

10.
Molecules ; 29(19)2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39407639

RESUMEN

In this study, four previously undescribed flavonoids, named epimesatines P (1), Q (2), R (3), and S (4), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were confirmed via spectroscopic analyses, quantum chemical electronic circular dichroism (ECD) calculations, Mo2(OAc)4-induced ECD, and Rh2(OCOCF3)4-induced ECD experiments. Epimesatines Q and R were characterized by the presence of furan rings. A cytotoxicity assay demonstrated that epimesatines P-S exhibited significant inhibitory effects on the viability of MCF-7 human breast cancer cells, with IC50 values ranging from 1.27 to 50.3 µM. Notably, epimesatines Q and R exhibited superior efficacy against MCF-7 cells compared to epimesatines P and S, suggesting that the presence of furan rings may enhance their activity against MCF-7 cells. Specifically, epimesatine Q displayed a more potent inhibitory effect at 1.27 µM compared to a positive control, docetaxel, which had an IC50 of 2.13 µM, highlighting its potential as a therapeutic agent for breast cancer. Importantly, none of the tested compounds exhibited obvious toxicity toward MCF-10A human breast epithelial cells. Furthermore, compounds 1, 3, and 4 were found to significantly inhibit the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells.


Asunto(s)
Epimedium , Flavonoides , Humanos , Epimedium/química , Flavonoides/farmacología , Flavonoides/química , Flavonoides/aislamiento & purificación , Células MCF-7 , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Estructura Molecular , Supervivencia Celular/efectos de los fármacos
11.
Am J Cancer Res ; 14(9): 4665-4682, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39417198

RESUMEN

Cervical cancer accounts for 10-15% of cancer-related mortality among women globally. Infection with high-risk human papillomavirus (HPV) types constitutes a significant etiological factor in the development of cervical carcinoma. The integration of HPV DNA into the host genome is considered a pivotal event in cervical carcinogenesis. Nevertheless, the precise mechanisms underlying HPV integration and its role in promoting cancer progression remain inadequately understood. Therefore, this study aims to identify potential common denominators at HPV DNA integration sites and to analyze the adjacent cellular sequences. We conducted whole-genome sequencing on 13 primary cervical cancer samples, employing the chromosomal coordinates of 537 breakpoints to assess the statistical overrepresentation of integration sites in relation to various chromatin features. Our analysis, which encompassed all chromosomes, identified several integration hotspots within the human genome, notably at 14q32.2, 10p15, and 2q37. Additionally, our findings indicated a preferential integration of HPV DNA into intragenic and gene-dense regions of human chromosomes. A substantial number of host cellular genes impacted by the integration sites were associated with cancer, including IKZF2, IL26, AHRR, and PDCD6. Furthermore, the cellular genes targeted by integration were enriched in tumor-related terms and pathways, as demonstrated by gene ontology and KEGG analysis. In conclusion, these findings enhance our understanding of HPV integration sites and provide deeper insights into the molecular mechanisms underlying the pathogenesis of cervical carcinoma.

12.
Phytochemistry ; : 114307, 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39442594

RESUMEN

Seven unreported compounds were isolated from dried flower buds of Ochrocarpus longifolius in this study, including an alkaloid ochrocaracid A (1), five coumarins ochrocarpins I (2), J (3), K (4), L (5), and M (6), and one styryl-2-pyranone compound iresinoacid (7) and nine known compounds (8-16). All these compounds were found in O. longifolius for the first time. Their structural elucidation was achieved through NMR, HR-ESI-MS, and ECD data. Additionally, a glucose uptake-promoting activity assay revealed that compounds 10 (128.21 µM) and 16 (123.15 µM) increased the glucose uptake capacity of L6 cells by 1.49-fold and 1.48-fold, respectively. These bioactive compounds could be potential candidates for further pharmaceutical applications.

13.
J Thorac Dis ; 16(9): 5539-5558, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39444875

RESUMEN

Background: Brain metastasis is a frequent complication in small cell lung cancer (SCLC), and there is an urgent need for new treatment modalities, given the limited success of traditional approaches. This study evaluates the combined efficacy and safety of brain radiotherapy (BRT), chemotherapy, and immune checkpoint inhibitors (ICIs) in the treatment of brain metastases in patients with extensive-stage SCLC (ES-SCLC). Additionally, it seeks to identify prognostic factors in these cases. Methods: A retrospective analysis was performed on 187 patients with ES-SCLC and brain metastases treated at Zhejiang Cancer Hospital from January 2017 to October 2023. Patients were divided into three groups based on their initial treatment: BRT alone, ICI alone, and a combined ICI + BRT approach, with chemotherapy included in all regimens. Variables such as age, number of brain metastases, symptoms, comorbidities, Karnofsky Performance Status (KPS) scores, smoking history, Graded Prognostic Assessment (GPA) scores, survival time, and treatment-related adverse events (TRAEs), including hematologic and hepatic toxicities were evaluated. Prognostic factors were assessed using univariate and multivariate analyses via Cox's proportional hazards model. The study also compared outcomes and TRAEs between patients undergoing synchronous treatment (ICI and BRT within four weeks) versus those with asynchronous therapy (more than four weeks apart). Results: Median overall survival (OS) times differed significantly across the groups: 11.6 months for BRT, 11.6 months for ICI, and 20.9 months for ICI + BRT (P<0.001). The ICI + BRT group also exhibited notably better progression-free survival (PFS) and intracranial PFS (iPFS), with medians of 12.6 and 14.9 months, respectively (P<0.001). This group demonstrated significantly improved systemic and intracranial objective response rates (ORR) and disease control rates (DCR). No significant differences in acute radiation injury rates were observed between the BRT and ICI + BRT groups. Multivariate analysis identified several factors influencing OS, including treatment regimen, number of chemotherapy and ICI cycles, presence of bone and multiple brain metastases, and antiangiogenesis therapies and extracranial radiotherapy. Both atezolizumab and serplulimab ICIs, in combination with various radiotherapy regimens [whole BRT (WBRT), WBRT with boost], were effective. Notably, asynchronous ICI and BRT treatment demonstrated advantages in PFS and iPFS over concurrent therapy, with no significant differences in other therapeutic indices or TRAE incidence rates. Conclusions: For ES-SCLC patients with synchronous brain metastases, combined ICI and BRT, alongside chemotherapy, surpasses the efficacy of either treatment alone with manageable TRAEs. Importantly, asynchronous ICI and BRT therapy showed superior outcomes compared to synchronous treatment modalities.

14.
Phytomedicine ; 135: 156129, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39427523

RESUMEN

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune condition characterized by inflammation and the deterioration of joints. Current treatments often have side effects, highlighting the need for safer options. This study investigates the therapeutic effects of Kunduan Yimu Decoction (KDYMD) on RA, focusing on the role of miR-124 in regulating Th17/Treg differentiation. METHODS: PBMCs from RA patients were analyzed before and after KDYMD treatment. RT-qPCR was used to measure the miR-124 expressions. Flow cytometry was used to assess the ratios of Th17 to Treg cells. ELISA was used to quantify the cytokine concentrations. The effects of KDYMD on JAK2/STAT3 signaling were evaluated by western blot analysis. A CIA mouse model was used to validate the in vivo effects of KDYMD. RESULTS: MiR-124 expression was significantly upregulated in PBMCs of RA patients after KDYMD treatment. This upregulation was associated with increased Tip60 and Foxp3 expression and decreased RORγt expression. In the cytokine analysis, IL-1, IL-6, and IL-17A were decreased, and IL-10 and TGF- were increased after treatment. Flow cytometry showed a restoration of the Th17/Treg balance, with a decrease in Th17 and an increase in Treg cells. In vivo, KDYMD treatment ameliorated ankle swelling and arthritis index in CIA mice, comparable to methotrexate (MTX). In addition, KDYMD modulated JAK2/STAT3 signaling and enhanced anti-inflammatory responses. CONCLUSIONS: KDYMD exerts significant anti-inflammatory effects in RA by upregulating miR-124, which in turn regulates Th17/Treg differentiation and modulates JAK2/STAT3 signaling. A novel mechanism involving miR-124 and immune cell balance suggests KDYMD could be a promising therapeutic agent for RA.

15.
Fitoterapia ; 179: 106247, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39395698

RESUMEN

Six undescribed compounds (1-6) and twenty-three known analogues (7-29) were isolated from the fresh roots of Rehmannia glutinosa. The structures of the compounds (1-29) were established through the application of spectroscopic analysis. Compounds 3, 4, 6, 8, 13, 18, 21, 22, 25, and 28 exhibited excellent anti-pulmonary fibrosis activity. The potential mechanistic pathway of 3 was also investigated, whose results indicate that compound 3 ameliorate TGF-ß1 induced BEAS-2B cell injury via PI3K/AKT/NF-κB signaling pathway.

16.
Nanomaterials (Basel) ; 14(19)2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39404327

RESUMEN

Carbon-based nanomaterials have garnered widespread attention and application because of their exceptional electrical conductivity, thermal conductivity, mechanical strength, and optical properties [...].

17.
Discov Med ; 36(189): 2098-2110, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39463230

RESUMEN

BACKGROUND: The impact of remifentanil on hypogastric flap function following ischemia-reperfusion (I/R) injury remains largely unknown, limiting its potential clinical application in flap surgery. This study investigated the therapeutic effects of remifentanil on hypogastric flap I/R injury. METHODS: Aortic endothelial cells were extracted from the hypogastric flap I/R injury models established in-house using Sprague-Dawley rats, and were treated under hypoxic conditions. The cells were treated with 0.1, 1, 10 and 100 ng/mL remifentanil and 10 ng/mL anisomycin (the activator of c-Jun N-terminal kinase [JNK]). Histopathological changes and tumor necrosis factor alpha (TNF-α) content of the flaps were observed after hematoxylin-eosin staining and immunohistochemistry. Immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry were employed for apoptosis evaluation. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were utilized to assess the protein and gene expression levels of TNF receptor 1 (TNFR1), JNK1, phosphorylated (p)-JNK1, malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO) and TNF-α in the flaps and cells. RESULTS: The endothelial necrosis and cell apoptosis of rat flaps induced by I/R injury were ameliorated by remifentanil, and declining aortic endothelial cell viability and augmented apoptosis induced by hypoxia were reversed by remifentanil (10, 100 ng/mL) (p < 0.05). Remifentanil reversed the increased expressions of TNFR1, JNK1, p-JNK1, MDA and TNF-α induced by I/R injury or hypoxia in the flaps and cells (p < 0.05), and counteracted the decreased levels of NO and SOD induced by I/R injury in the flaps (p < 0.05). Anisomycin reversed the effects of remifentanil on suppressing TNFR1, JNK1 and p-JNK1 levels and apoptosis in the cells (p < 0.05). CONCLUSION: Remifentanil ameliorates cell apoptosis and vascular endothelial necrosis induced by I/R injury in the hypogastric flap, likely by downregulating the TNF-α/TNFR1 pathway and JNK1 signaling. These findings suggest that remifentanil may be a promising therapeutic agent for improving hypogastric flap survival in clinical settings.


Asunto(s)
Apoptosis , Ratas Sprague-Dawley , Remifentanilo , Daño por Reperfusión , Animales , Remifentanilo/farmacología , Daño por Reperfusión/patología , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Ratas , Masculino , Apoptosis/efectos de los fármacos , Colgajos Quirúrgicos/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Piperidinas/farmacología , Piperidinas/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Transducción de Señal/efectos de los fármacos
18.
Molecules ; 29(20)2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39459279

RESUMEN

Bismuth-based photocatalytic materials have been widely used in the field of photocatalysis in recent years due to their unique layered structure. However, single bismuth-based photocatalytic materials are greatly limited in their photocatalytic performance due to their poor response to visible light and easy recombination of photogenerated charges. At present, constructing semiconductor heterojunctions is an effective modification method that improves quantum efficiency by promoting the separation of photogenerated electrons and holes. In this study, the successful preparation of an In2O3/Bi2WO6 (In2O3/BWO) II-type semiconductor heterojunction composite material was achieved. XRD characterization was performed to conduct a phase analysis of the samples, SEM and TEM characterization for a morphology analysis of the samples, and DRS and XPS testing for optical property and elemental valence state analyses of the samples. In the II-type semiconductor junction system, photogenerated electrons (e-) on the In2O3 conduction band (CB) migrate to the BWO CB, while holes (h+) on the BWO valence band (VB) transfer to the In2O3 VB, promoting the separation of photoinduced charges, raising the quantum efficiency. When the molar ratio of In2O3/BWO is 2:6, the photocatalytic degradation degree of rhodamine B (RhB) is 59.4% (44.0% for BWO) after 60 min illumination, showing the best photocatalytic activity. After four cycles, the degradation degree of the sample was 54.3%, which is 91.4% of that of the first photocatalytic degradation experiment, indicating that the sample has good reusability. The XRD results of 2:6 In2O3/BWO before and after the cyclic experiments show that the positions and intensities of its diffraction peaks did not change significantly, indicating excellent structural stability. The active species experiment results imply that h+ is the primary species. Additionally, this study proposes a mechanism for the separation, migration, and photocatalysis of photoinduced charges in II-type semiconductor junctions.

19.
Pharmaceutics ; 16(10)2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39458634

RESUMEN

BACKGROUND/OBJECTIVES: Numerical simulation plays an important role in pharmaceutical preparation recently. Mechanistic models, as a type of numerical model, are widely used in the study of pharmaceutical preparations. Mechanistic models are based on a priori knowledge, i.e., laws of physics, chemistry, and biology. However, due to interdisciplinary reasons, pharmacy researchers have greater difficulties in using computer models. METHODS: In this paper, we highlight the application scenarios and examples of mechanistic modelling in pharmacy research and provide a reference for drug researchers to get started. RESULTS: By establishing a suitable model and inputting preparation parameters, researchers can analyze the drug preparation process. Therefore, mechanistic models are effective tools to optimize the preparation parameters and predict potential quality problems of the product. With product quality parameters as the ultimate goal, the experiment design is optimized by mechanistic models. This process emphasizes the concept of quality by design. CONCLUSIONS: The use of numerical simulation saves experimental cost and time, and speeds up the experimental process. In pharmacy experiments, part of the physical information and the change processes are difficult to obtain, such as the mechanical phenomena during tablet compression and the airflow details in the nasal cavity. Therefore, it is necessary to predict the information and guide the formulation with the help of mechanistic models.

20.
J Cell Sci ; 2024 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-39479887

RESUMEN

Microtubules are vital components of the cytoskeleton. Their plus ends are dynamic and respond to changes in cell morphology, while the minus ends are stable and serve a crucial role in microtubule seeding and maintaining spatial organization. In mammalian cells, the calmodulin-regulated spectrin-associated proteins (CAMSAPs), play a key role in directly regulating the dynamics of non-centrosomal microtubules minus ends. However, the molecular mechanisms are not yet fully understood. Our study reveals that CAMSAP3 forms dimers through its C-terminal α-helix; this dimerization not only enhances the microtubule-binding affinity of the CKK domain but also enables the CKK domain to regulate the dynamics of microtubules. Furthermore, CAMSAP3 also specializes in decorating at the minus end of microtubules through the combined action of the microtubule-binding domain (MBD) and the C-terminal α-helix, thereby achieving dynamic regulation of the minus ends of microtubules. These findings are crucial for advancing our understanding and treatment of diseases associated with non-centrosomal microtubules.

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