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1.
Front Oncol ; 14: 1396281, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38725617

RESUMEN

Background: Very well-differentiated gastric adenocarcinoma (VWDA) is a rare variant of gastric cancer, for which the diagnostic criteria and clinical behavior are not fully established. We reported a case of an intramucosal VWDA of gastric type with a lymphovascular invasion (LVI). Case presentation: A 67-year-old female was diagnosed as intramucosal gastric adenocarcinoma after a biopsy at the local hospital 3 weeks ago and then visited our hospital for further treatment. The endoscopic examination in our hospital showed a rough, slightly faded, 30-mm, flat, and elevated lesion on the lesser curvature of the middle gastric body. Histopathologically, the lesion consisted of superficial foveolar-type papillary adenocarcinoma and deep pyloric gland-type tubular adenocarcinoma. The immunostaining results showed that the foveolar-type papillary adenocarcinoma was positive for MUC5AC and had a high index of Ki-67, but the pyloric gland-type tubular adenocarcinoma was positive for MUC6 and had a low index of Ki-67. Both components were negative for MSH2 and MSH6, which suggested the high microsatellite instability phenotype. Moreover, a LVI was detected in the lesion. The pathological diagnosis was VWDA of gastric type. Conclusion: The case has unique histological and immunophenotypic characteristics, which not only indicates the importance of architectural features in the diagnosis of VWDA but also further proves that the aggressive behavior of VWDA is correlated with tumor histological type and immunophenotype.

2.
Colloids Surf B Biointerfaces ; 239: 113953, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38729021

RESUMEN

Ascorbic acid (AA) is a powerful antioxidant in food safety and disease treatment. It is of great significance to develop a low-cost, high-stability, and easy-to-operate colorimetric method for quantitative detection of AA in food or human body. Although various nanozymes have been developed for the colorimetric detection of AA, the size regulation of the catalytic center of nanozymes remains a challenge. In this work, we propose a combined strategy of flow chemistry synthesis and pyrolysis to realize the controllable adjustment of the catalytic center size of nanozymes. Zinc-cobalt zeolitic imidazole frameworks (ZnCo-ZIFs) with different sizes are synthesized by flow chemistry. Nitrogen-doped carbon materials with different Co catalytic centers (80 nm-10 nm) are then obtained by pyrolysis of ZnCo-ZIFs precursors. Among them, cobalt quantum dot embedded nitrogen-doped carbon (Co QDs/N-C) exhibits excellent oxidase activity, with Vmax and Km of 4.19 × 10-7 M s-1 and 0.12 mM. Therefore, a simple, low-cost, and stable colorimetric method for the detection of AA is established with a good linear relationship (3-500 µM) and low detection limit (0.40 µM). This work has certain guiding significance for the size regulation of catalytic center of nanozyme, and the detection method has broad application prospects in biochemical sensing field.

3.
PLoS Med ; 21(5): e1004389, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38728364

RESUMEN

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina , Cetuximab , Neoplasias Colorrectales , Fluorouracilo , Leucovorina , Neoplasias Hepáticas , Compuestos Organoplatinos , Proteínas Proto-Oncogénicas B-raf , Humanos , Cetuximab/administración & dosificación , Cetuximab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/tratamiento farmacológico , Femenino , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Proteínas Proto-Oncogénicas B-raf/genética , Anciano , Adulto , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/administración & dosificación , Resultado del Tratamiento , Proteínas ras/genética
4.
Gene ; : 148544, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38734187

RESUMEN

This study introduces an efficient RPA-PfAgo detection system for the MTHFR C677T polymorphism, proposing a potential strategy to simplify the genotyping process. By optimizing recombinase polymerase amplification (RPA) with Pyrococcus furiosus Argonaute (PfAgo) nucleases, we achieved DNA amplification at a constant temperature. The assay was fine-tuned through meticulous primer and guide DNA selection, with optimal conditions established at 2.0 µL of MgAc, a reaction temperature of 42 °C, and a 10-minute reaction time for RPA. Further optimization of the PfAgo cleavage assay revealed the ideal concentrations of MnCl2, guide DNA, molecular beacon probes, the PfAgo enzyme, and the RPA product to maximize sensitivity and specificity. Clinical validation of 20 samples showed 100 % concordance with Sanger sequencing, confirming the method's precision. The RPA-PfAgo system is a promising tool for on-site genotyping, with broad applications in personalized medicine and disease prevention.

5.
Front Immunol ; 15: 1345381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736890

RESUMEN

Sjögren's syndrome (SS) is a chronic systemic autoimmune disease that typically presents with lymphocyte, dendritic cell, and macrophage infiltration of exocrine gland ducts and the formation of ectopic germinal centers. The interactions of lymphocyte homing receptors and addressins and chemokines and their receptors, such as α4ß7/MAdCAM-1, LFA-1/ICAM-1, CXCL13/CXCR5, CCL25/CCR9, CX3CL1/CX3CR1, play important roles in the migration of inflammatory cells to the focal glands and the promotion of ectopic germinal center formation in SS. A variety of molecules have been shown to be involved in lymphocyte homing, including tumor necrosis factor-α, interferon (IFN)-α, IFN-ß, and B cell activating factor. This process mainly involves the Janus kinase-signal transducer and activator of transcription signaling pathway, lymphotoxin-ß receptor pathway, and nuclear factor-κB signaling pathway. These findings have led to the development of antibodies to cell adhesion molecules, antagonists of chemokines and their receptors, compounds interfering with chemokine receptor signaling, and gene therapies targeting chemokines and their receptors, providing new targets for the treatment of SS in humans. The aim of this study was to explore the relationship between lymphocyte homing and the pathogenesis of SS, and to provide a review of recent studies addressing lymphocyte homing in targeted therapy for SS.


Asunto(s)
Quimiocinas , Síndrome de Sjögren , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/metabolismo , Humanos , Quimiocinas/metabolismo , Quimiocinas/inmunología , Transducción de Señal , Animales , Receptores Mensajeros de Linfocitos/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Receptores de Quimiocina/metabolismo , Receptores de Quimiocina/inmunología
6.
Chem Commun (Camb) ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764428

RESUMEN

An innovative method to improve the oxidation efficiency of benzyl alcohol utilizes Ni-Co hexacyanoferrate hollow nanoprisms. Synthesized via a gentle self-sacrificial template method, this catalyst exhibits substantial catalytic activity and selectivity towards benzyl alcohol oxidation, facilitated by the strategic incorporation of Co to modulate CN vacancy density. Impressively, it achieves a current density of 10 mA cm-2 at 1.33 V and a remarkable 98% efficiency in benzyl alcohol conversion at 1.4 V.

7.
Sensors (Basel) ; 24(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38732884

RESUMEN

The performance of the tire has a very important impact on the safe driving of the car, and in the actual use of the tire, due to complex road conditions or use conditions, it will inevitably cause immeasurable wear, scratches and other damage. In order to effectively detect the damage existing in the key parts of the tire, a tire surface damage detection method based on image processing was proposed. In this method, the image of tire side is captured by camera first. Then, the collected images are preprocessed by optimizing the multi-scale bilateral filtering algorithm to enhance the detailed information of the damaged area, and the optimization effect is obvious. Thirdly, the image segmentation based on clustering algorithm is carried out. Finally, the Harris corner detection method is used to capture the "salt and pepper" corner of the target region, and the segmsegmed binary image is screened and matched based on histogram correlation, and the target region is finally obtained. The experimental results show that the similarity detection is accurate, and the damage area can meet the requirements of accurate identification.

8.
Food Funct ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738935

RESUMEN

Inflammatory bowel disease (IBD) comprises a group of highly prevalent and chronic inflammatory intestinal tract diseases caused by multiple factors. Despite extensive research into the causes of the disease, IBD's pathogenic mechanisms remain unclear. Moreover, side effects of current IBD therapies restrict their long-term clinical use. In contrast, natural polysaccharides exert beneficial anti-IBD effects and offer advantages over current anti-IBD drugs, including enhanced safety and straightforward isolation from abundant and reliable sources, and thus may serve as components of functional foods and health products for use in IBD prevention and treatment. However, few reviews have explored natural polysaccharides with anti-IBD activities or the relationship between polysaccharide conformation and anti-IBD biological activity. Therefore, this review aims to summarize anti-IBD activities and potential clinical applications of polysaccharides isolated from plant, animal, microorganismal, and algal sources, while also exploring the relationship between polysaccharide conformation and anti-IBD bioactivity for the first time. Furthermore, potential mechanisms underlying polysaccharide anti-IBD effects are summarized, including intestinal microbiota modulation, intestinal inflammation alleviation, and intestinal barrier protection from IBD-induced damage. Ultimately, this review provides a theoretical foundation and valuable insights to guide the development of natural polysaccharide-containing functional foods and nutraceuticals for use as dietary IBD therapies.

9.
Endocrine ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758293

RESUMEN

PURPOSE: The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults. METHODS: This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types. RESULTS: Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses. CONCLUSION: We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.

10.
J Robot Surg ; 18(1): 193, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38693446

RESUMEN

Conducting clinical trials can evaluate the effectiveness and safety of surgical robots. To promote the advancement of academic robotic programs in surgery, this study captures the development trend and research hotspots of clinical trials related to surgical robots by bibliometric analysis. Bibliometrix package in R software was used to analyze the publication year, authors, countries, institutes, and journals. The visualization maps of keywords were formed using VOSviewer. The keywords with the strongest citation bursts and the institutional collaboration map were created by CiteSpace. Urology dominates with 31.3% of publications and the controlled clinical trials in urology and orthopedic accounted for the highest proportion, reaching 73%. North America, the USA, and Seoul National University lead in productivity. The most productive country, region and institution are North America, USA and Seoul National University, respectively. The trend of collaboration is regional instead of international. Keyword and burst keyword analysis revealed a primary focus in clinical research on robotic surgery: evaluating process improvements, comparing robotic and traditional surgery, and assessing feasibility. Long-term clinical trials assess surgical robots not only intraoperative performance but also postoperative complications and overall surgical outcomes. The development in the field is unbalanced between regions and countries. To promote multi-center clinical trials, governments can streamline review procedures and establish international consensus review standards, while academic institutions can form academic alliances. Also, the study offers recommendations for the development of academic robotic programs and regional collaboration units in robotic surgery, which may provide researchers with a strong reference for future research.


Asunto(s)
Bibliometría , Ensayos Clínicos como Asunto , Procedimientos Quirúrgicos Robotizados , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/tendencias , Humanos
11.
Nat Plants ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714768

RESUMEN

Phytochrome A (phyA) is the plant far-red (FR) light photoreceptor and plays an essential role in regulating photomorphogenic development in FR-rich conditions, such as canopy shade. It has long been observed that phyA is a phosphoprotein in vivo; however, the protein kinases that could phosphorylate phyA remain largely unknown. Here we show that a small protein kinase family, consisting of four members named PHOTOREGULATORY PROTEIN KINASES (PPKs) (also known as MUT9-LIKE KINASES), directly phosphorylate phyA in vitro and in vivo. In addition, TANDEM ZINC-FINGER/PLUS3 (TZP), a recently characterized phyA-interacting protein required for in vivo phosphorylation of phyA, is also directly phosphorylated by PPKs. We reveal that TZP contains two intrinsically disordered regions in its amino-terminal domain that undergo liquid-liquid phase separation (LLPS) upon light exposure. The LLPS of TZP promotes colocalization and interaction between PPKs and phyA, thus facilitating PPK-mediated phosphorylation of phyA in FR light. Our study identifies PPKs as a class of protein kinases mediating the phosphorylation of phyA and demonstrates that the LLPS of TZP contributes significantly to more production of the phosphorylated phyA form in FR light.

12.
Leuk Res ; 141: 107499, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38640632

RESUMEN

Acute myeloid leukemia (AML) is a hematopoietic malignancy with a high relapse rate and progressive drug resistance. Alternative polyadenylation (APA) contributes to post-transcriptional dysregulation, but little is known about the association between APA and AML. The APA quantitative trait locus (apaQTL) is a powerful method to investigate the relationship between APA and single nucleotide polymorphisms (SNPs). We quantified APA usage in 195 Chinese AML patients and identified 4922 cis-apaQTLs related to 1875 genes, most of which were newly reported. Cis-apaQTLs may modulate the APA selection of 115 genes through poly(A) signals. Colocalization analysis revealed that cis-apaQTLs colocalized with cis-eQTLs may regulate gene expression by affecting miRNA binding sites or RNA secondary structures. We discovered 207 cis-apaQTLs related to AML risk by comparing genotype frequency with the East Asian healthy controls from the 1000 Genomes Project. Genes with cis-apaQTLs were associated with hematological phenotypes and tumor incidence according to the PHARMGKB and MGI databases. Collectively, we profiled an atlas of cis-apaQTLs in Asian AML patients and found their association with APA selection, gene expression, AML risk, and complex traits. Cis-apaQTLs may provide insights into the regulatory mechanisms related to APA in AML occurrence, progression, and prognosis.

13.
Artículo en Inglés | MEDLINE | ID: mdl-38626346

RESUMEN

Background: The incidence of chronic obstructive pulmonary disease (COPD) and osteoporosis are rising worldwide. Observational studies showed that COPD is associated with increased risk of osteoporosis. We performed the Mendelian randomization (MR) study to genetically investigate the causality of COPD on osteoporosis. Methods: We explored the causal effect of COPD on osteoporosis by the MR analysis. A total of 108 genetic loci single nucleotide polymorphisms were related to COPD. The primary approach in this MR analysis was the inverse variance-weighted (IVW) method. Simple median, weighted median, MR Egger and penalized weighted median analyzed the sensitivity. Results: The study found that genetically predicted COPD is causally linked to an increased risk of osteoporosis, as evidenced by both the fixed-effect IVW model and random-effect IVW model (odds ratio [OR], 1.010; 95% CI, 1.001-1.019, P=0.021; OR, 1.010; 95% CI, 1.001-1.020, P=0.039). This association was also observed in other methods, including the simple median, weighted median, Penalised weighted median, MR-Egger method, and MR Egger (bootstrap) method. The results of the IVW and MR-Egger analyses showed no heterogeneity (Q=131.374, P=0.061 and Q=128.895, P=0.069, respectively). Additionally, MR-Egger regression did not reveal any pleiotropic influence through genetic variants (intercept, -0.004; P=0.101). Lastly, the leave-one-out sensitivity analysis did not identify any individual SNP that significantly influenced the association between COPD and osteoporosis. Conclusion: The Mendelian randomization analysis showed a significant detrimental effect of COPD on the risk of osteoporosis.

14.
Biochem Pharmacol ; 223: 116193, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38582268

RESUMEN

Ovarian aging leads to infertility and birth defects. We aimed to clarify the role of Indole-3-carbinol (I3C) in resistance to oxidative stress, apoptosis, and fibrosis in ovarian aging. I3C was administered via intraperitoneal injection for 3 weeks in young or old mice. Immunohistochemistry; Masson, Sirius red, and TUNEL staining; follicle counting; estrous cycle analysis; and Western blotting were used for validating the protective effect of I3C against ovarian senescence. Human granulosa-like tumor cell line and primary granulosa cells were used for in vitro assay. The results indicated that I3C inhibited ovarian fibrosis and apoptosis while increasing the number of primordial follicles. Mechanistic studies have shown that I3C promoted the nuclear translocation of nuclear factor-erythroid 2-related factor (Nrf2) and upregulated the expression of heme oxygenase 1 (HO-1). Additionally, I3C increased cell viability and decreased lactate dehydrogenase, malondialdehyde, reactive oxygen species and JC-1 levels. Furthermore, the antioxidant effect of I3C was found to be dependent on the activation of Nrf2 and HO-1, as demonstrated by the disappearance of the effect upon inhibition of Nrf2 expression. In conclusion, I3C can alleviate the ovarian damage caused by aging and may be a protective agent to delay ovarian aging.


Asunto(s)
Hemo-Oxigenasa 1 , Indoles , Factor 2 Relacionado con NF-E2 , Ratones , Femenino , Humanos , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Hemo-Oxigenasa 1/metabolismo , Estrés Oxidativo , Fibrosis , Apoptosis
15.
Int J Biol Macromol ; 268(Pt 1): 131503, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38663697

RESUMEN

Herbivorous insects utilize intricate olfactory mechanisms to locate food plants. The chemical communication of insect-plant in primitive lineage offers insights into evolutionary milestones of divergent olfactory modalities. Here, we focus on a system endemic to the Qinghai-Tibetan Plateau to unravel the chemical and molecular basis of food preference in ancestral Lepidoptera. We conducted volatile profiling, neural electrophysiology, and chemotaxis assays with a panel of host plant organs to identify attractants for Himalaya ghost moth Thitarodes xiaojinensis larvae, the primitive host of medicinal Ophiocordyceps sinensis fungus. Using a DREAM approach based on odorant induced transcriptomes and subsequent deorphanization tests, we elucidated the odorant receptors responsible for coding bioactive volatiles. Contrary to allocation signals in most plant-feeding insects, T. xiaojinensis larvae utilize tricosane from the bulbil as the main attractant for locating native host plant. We deorphanized a TxiaOR17b, an indispensable odorant receptor resulting from tandem duplication of OR17, for transducing olfactory signals in response to tricosane. The discovery of this ligand-receptor pair suggests a survival strategy based on food location via olfaction in ancestral Lepidoptera, which synchronizes both plant asexual reproduction and peak hatch periods of insect larvae.


Asunto(s)
Larva , Mariposas Nocturnas , Receptores Odorantes , Animales , Mariposas Nocturnas/fisiología , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Olfato/fisiología , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Proteínas de Insectos/química , Filogenia , Quimiotaxis , Alcoholes Grasos/farmacología , Alcoholes Grasos/química
16.
J Nanobiotechnology ; 22(1): 195, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643173

RESUMEN

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-ß-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.


Asunto(s)
Cardiomiopatías , Células Madre Pluripotentes Inducidas , MicroARNs , Humanos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Cardiomiopatías/inducido químicamente , Transducción de Señal , Doxorrubicina
17.
BMC Pregnancy Childbirth ; 24(1): 236, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575874

RESUMEN

BACKGROUND: To analyze the impact of the time of natural cessation of the umbilical cord on maternal and infant outcomes in order to explore the time of clamping that would be beneficial to maternal and infant outcomes. METHODS: The study was a cohort study and pregnant women who met the inclusion and exclusion criteria at the Obstetrics and Gynecology Department of Qilu Hospital of Shandong University from September 2020 to September 2021. Analysis using Kruskal-Wallis rank sum test, Pearson's Chi-squared test, generalized linear mixed model (GLMM) and repeated measures ANOVA. If the difference between groups was statistically significant, the Bonferroni test was then performed. A two-sided test of P < 0.05 was considered statistically significant. RESULTS: A total of 345 pregnants were included in this study. The subjects were divided into the ≤60 seconds group (n = 134), the 61-89 seconds group (n = 106) and the ≥90 seconds group (n = 105) according to the time of natural arrest of the umbilical cord. There was no statistically significant difference in the amount of postpartum hemorrhage and the need for iron, medication, or supplements in the postpartum period between the different cord spontaneous arrest time groups for mothers (P > 0.05). The weight of the newborns in the three groups was (3316.27 ± 356.70) g, (3387.26 ± 379.20) g, and (3455.52 ± 363.78) g, respectively, and the number of days of cord detachment was 12.00 (8.00, 15.75) days, 10.00 (7.00, 15.00) days and 9.00 (7.00, 13.00) days, respectively, as the time of natural cessation of the cord increased. The neonatal lymphocyte ratio, erythrocyte pressure, and hemoglobin reached a maximum in the 61-89 s group at (7.41 ± 2.16) %, (61.77 ± 8.17) % and (194.52 ± 25.84) g/L, respectively. Lower incidence of neonatal hyperbilirubinemia in the 61-89 s group compared to the ≥90s group 0 vs 4.8 (P < 0.05). CONCLUSIONS: In full-term singleton vaginal births, maternal and infant outcomes are better when waiting for 61-89 s after birth for the cord to stop pulsating naturally, suggesting that we can wait up to 90s for the cord to stop pulsating naturally, and if the cord does not stop pulsating after 90s, artificial weaning may be more beneficial to maternal and infant outcomes.


Asunto(s)
Hemorragia Posparto , Cordón Umbilical , Lactante , Recién Nacido , Embarazo , Humanos , Femenino , Estudios de Cohortes , Estudios Prospectivos , Nacimiento a Término
18.
Nano Lett ; 24(17): 5371-5378, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38647348

RESUMEN

Artificial synapses and bionic neurons offer great potential in highly efficient computing paradigms. However, complex requirements for specific electronic devices in neuromorphic computing have made memristors face the challenge of process simplification and universality. Herein, reconfigurable Ag/HfO2/NiO/Pt memristors are designed for feasible switching between volatile and nonvolatile modes by compliance current controlled Ag filaments, which enables stable and reconfigurable synaptic and neuronal functions. A neuromorphic computing system effectively replicates the biological synaptic weight alteration and continuously accomplishes excitation and reset of artificial neurons, which consist of bionic synapses and artificial neurons based on isotype Ag/HfO2/NiO/Pt memristors. This reconfigurable electrical performance of the Ag/HfO2/NiO/Pt memristors takes advantage of simplified hardware design and delivers integrated circuits with high density, which exhibits great potency for future neural networks.

19.
Insights Imaging ; 15(1): 109, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38679659

RESUMEN

OBJECTIVE: To determine whether quantitative parameters of detector-derived dual-layer spectral computed tomography (DLCT) can reliably identify epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC who underwent arterial phase (AP) and venous phase (VP) DLCT between December 2021 and November 2022 were subdivided into the mutated and wild-type EGFR groups following EGFR mutation testing. Their baseline clinical data, conventional CT images, and spectral images were obtained. Iodine concentration (IC), iodine no water (INW), effective atomic number (Zeff), virtual monoenergetic images, the slope of the spectral attenuation curve (λHU), enhancement degree (ED), arterial enhancement fraction (AEF), and normalized AEF (NAEF) were measured for each lesion. RESULTS: Ninety-two patients (median age, 61 years, interquartile range [51, 67]; 33 men) were evaluated. The univariate analysis indicated that IC, normalized IC (NIC), INW and ED for the AP and VP, as well as Zeff and λHU for the VP were significantly associated with EGFR mutation status (all p < 0.05). INW(VP) showed the best diagnostic performance (AUC, 0.892 [95% confidence interval {CI}: 0.823, 0.960]). However, neither AEF (p = 0.156) nor NAEF (p = 0.567) showed significant differences between the two groups. The multivariate analysis showed that INW(AP) and NIC(VP) were significant predictors of EGFR mutation status, with the latter showing better performance (p = 0.029; AUC, 0.897 [95% CI: 0.816, 0.951] vs. 0.774 [95% CI: 0.675, 0.855]). CONCLUSION: Quantitative parameters of DLCT can help predict EGFR mutation status in patients with NSCLC. CRITICAL RELEVANCE STATEMENT: Quantitative parameters of DLCT, especially NIC(VP), can help predict EGFR mutation status in patients with NSCLC, facilitating appropriate and individualized treatment for them. KEY POINTS: Determining EGFR mutation status in patients with NSCLC before starting therapy is essential. Quantitative parameters of DLCT can predict EGFR mutation status in NSCLC patients. NIC in venous phase is an important parameter to guide individualized treatment selection for NSCLC patients.

20.
Materials (Basel) ; 17(8)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38673257

RESUMEN

Microwave heating is an emerging alternative pretreatment method for road maintenance in cold seasons. The thermal behavior of asphalt pavement under microwave heating is mainly determined by the complex permittivity of the asphalt mixture. In this study, an innovative approach for calculating the complex permittivity of an asphalt mixture based on a three-dimensional meso-scale heterogeneous structure was proposed. A series of experiments was conducted to verify the accuracy of this approach. The effect of porosity, void size, moisture content and aggregate gradation on the complex permittivity for an asphalt mixture were computationally analyzed based on the validated approach. Moreover, the applicability of commonly used classical dielectric models was analyzed. The classical Lichtenecker-Rother (LR) dielectric model was modified on the basis of simulation data for various conditions. The results showed that the real part of the complex permittivity decreased with the increase in porosity. Some sudden change in the imaginary part of the complex permittivity was observed within the frequency range from 2.6 GHz to 3.9 GHz. A larger air void size would lead to a larger frequency at which sudden change occurs. The real part and imaginary part of the complex permittivity tend to be smaller when more coarse aggregates are replaced with fine aggregates. Both the real part and the imaginary part of the complex permittivity increase with higher moisture content due to the stronger dielectric property of water. Each 1% increase in moisture content would lead to about a 3~4% increase in the real part of the complex permittivity. The determination coefficients R2 for the real part and the imaginary part of the complex permittivity fitted by the modified Brown model were the maximum values, which were 0.922 and 0.980, respectively. The method presented in this study is useful for transportation agencies to optimize microwave heating during winter maintenance.

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