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1.
World J Clin Cases ; 12(25): 5769-5774, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39247731

RESUMEN

BACKGROUND: Gynaecologists should be aware of a rare obstructive Mullerian duct abnormality like Robert's uterus and perform further surgery when necessary. CASE SUMMARY: We report a 41-year-old mother of two children with Robert's uterus who was examined and treated by laparoscopy and hysteroscopy. Unlike the existing cases reported in the literature, this patient had a late onset of Robert's uterus symptoms. Due to right tubal ectopic pregnancy 3 years previously, the patient was treated with right salpingectomy and left tubal ligation but suffered aggravated left lower abdominal pain. She was examined and treated by laparoscopy and hysteroscopy, and is completely asymptomatic at 5-year follow-up. CONCLUSION: The typical obstructive Mullerian abnormality requires further surgery. Combined laparoscopy and hysteroscopy is an effective, minimally invasive technique with better recovery outcomes than traditional transabdominal procedures.

2.
Food Res Int ; 194: 114907, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39232532

RESUMEN

Methylglyoxal (MG) serves as the primary precursor for the nonenzymatic glycation of proteins and DNA, leading to advanced glycation end products (AGEs). Regular intake of dietary MG is strongly correlated with low-grade inflammation, potentially accelerating the pathogenesis of metabolic diseases, including obesity, diabetes, cancers, liver diseases, Alzheimer's disease, cardiovascular diseases, aging, and bone loss. Although pharmaceutical agents (pimagedine and candesartan) have been developed to inhibit MG formation, they often come with serious side effects (nausea, diarrhea, headache, gastrointestinal disturbance, symptomatic hypotension, abnormal renal and liver function tests, development of antinuclear antibody, pernicious-like anemia, and hyperkalemia), highlighting the need for an efficient and safe approach to scavenging MG. Phyllanthus emblica Linn fruit, a nutritious edible fruit, and medicinal plant contains over 300 bioactive compounds. Among twenty-three herbals, 100 µg/mL of the aqueous extract of Phyllanthus emblica fruit (APF) exhibits the highest potency in trapping MG, achieving an 87.3 % reduction under d-fructose induced BSA-AGEs formation. However, there are few reports detailing APF and its related foods' specific impact on disease prevention through MG trapping. This review summarizes the mechanisms through which MG is linked to the development of metabolic diseases and provides several strategies for reducing MG levels using APF and its bioactive compounds. The potential antiglycation properties of APF may offer new applications in the food industry and pharmacological research.


Asunto(s)
Frutas , Enfermedades Metabólicas , Phyllanthus emblica , Extractos Vegetales , Piruvaldehído , Phyllanthus emblica/química , Piruvaldehído/metabolismo , Humanos , Extractos Vegetales/farmacología , Enfermedades Metabólicas/prevención & control , Frutas/química , Productos Finales de Glicación Avanzada/metabolismo , Animales
3.
Small ; : e2406545, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39282814

RESUMEN

Artificial DNA circuits represent a versatile yet promising toolbox for in situ monitoring and concomitant regulation of diverse biological events within live cells. Nonetheless, their performance is significantly impeded by the diffusion-dominated slow reaction kinetics and the uncontrollable off-target activation. Herein, a self-localized cascade (SLC) circuit is reported for the robust and efficient microRNA (miRNA) analysis in living cells. The SLC circuit consists of the cell-specific localization module and the analyte-specific signal amplification module. By integrating the reaction probes of these two modules, the complexity of the system is reduced to realize the responsive co-localization of circuitry probes and the simultaneous cascade signal amplification. Taking advantage of the specifically activated, self-localized, and cascade design, the SLC circuit successfully achieves the robust miRNA-21 (miR-21) imaging and the accurate cells differentiation. Moreover, the reverse regulation mechanism is successfully explored between messenger RNA (mRNA) and miRNA through the engineered SLC circuit and further elucidates the underlying signaling pathways between them. Therefore, the SLC circuit provides a powerful tool for the sensitive detection of intracellular biomolecules and the study of the corresponding cell regulatory mechanisms.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39284768

RESUMEN

Abdominal wall scar endometriosis (AWE) is a rare endometriosis that usually occurs after gynecological or obstetric surgery and for which surgical resection is the standard treatment. For large tissue defects after resection, abdominal wall reconstruction is needed. Here, we describe a mesh bridging technique using biological and polypropylene meshes for abdominal wall reconstruction. A 34-year-old woman visited the center with complaints of low abdominal wall pain during menstruation for more than 5 years. Her surgical history included undergoing a cesarean section delivery twice. A mass measuring 6 cm × 5 cm × 3 cm was found above the symphysis pubis in the lower part of the abdominal incision. Endometriosis lesion was considered based on abdominal ultrasound and magnetic resonance imaging findings. After a multidisciplinary discussion that included surgical experts and gynecologists, the decision was made to perform abdominal endometrial focus excision plus abdominal wall reconstruction. Two kinds of mesh were skillfully used in the operation of this patient. Biological mesh was used close to the peritoneal side and covered with polypropylene mesh to reduce the stimulation by the polypropylene mesh of the peritoneum, enhance the strength of the biological mesh, and reduce the incidence of abdominal wall hernia. Our case demonstrates that accurate diagnosis of AWE followed by complete resection and reconstruction of the abdominal wall using a combination of biological and polypropylene mesh bridging can achieve good therapeutic results and patient satisfaction.

5.
Front Cardiovasc Med ; 11: 1421025, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267800

RESUMEN

Background: The role of routine intravascular imaging in percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) remains unclear. This study evaluated the clinical outcomes of PCI guided by different imaging modalities in AMI patients. Materials and methods: Data from AMI patients who had undergone PCI between 2012 and 2022 were analyzed. The mean follow-up was 12.9 ± 1.73 months. The imaging modality-either intravascular ultrasound (IVUS), optical coherence tomography (OCT), or angiography alone-was selected at the operator's discretion. The primary endpoint was major adverse cardiac events (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), target vessel revascularization. Results: Of the 1,304 PCIs performed, 47.5% (n = 620) were guided by angiography alone, 37.0% (n = 483) by IVUS, and 15.4% (n = 201) by OCT. PCI guided by intravascular imaging modalities was associated with lower 1-year rates of MI (1.3%, P = 0.001) and MACE (5.2%, P = 0.036). OCT-guided PCI was linked to lower rates of 1-year CV death (IVUS vs. OCT: 6.2% vs. 1.5%, P = 0.016) and MACE (IVUS vs. OCT: 6.4% vs. 2.5%, P = 0.032). Intravascular imaging modalities and diabetes were identified as predictors of better and worse 1-year MACE outcomes, respectively. Conclusion: PCI guided by intravascular imaging modalities resulted in improved 1-year clinical outcomes compared to angiography-guided PCI alone in AMI patients. OCT-guided PCI was associated with lower 1-year MACE rates compared to IVUS-guided PCI. Therefore, intravascular imaging should be recommended for PCI in AMI, with OCT being particularly considered when appropriate.

6.
Front Pharmacol ; 15: 1377501, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234114

RESUMEN

Introduction: Chronic alcoholism is one of the most common neurological diseases in modern society. However, the key mechanisms underlying learning and memory impairments caused by chronic alcohol exposure remain unclear. In this study, a microRNA-messenger RNA (miRNA-mRNA) network was constructed to explore the potential function of key genes in chronic alcohol exposure, their effects on the hippocampus, and their mechanisms which facilitate brain injury in mice. Methods: The Morris water maze test was used to assess the learning ability of mice in each group. Mitochondrial ATPase activity and H2S levels in the hippocampi of mice were determined. Differentially expressed miRNAs and mRNAs in the mouse hippocampus were identified using second-generation sequencing. Using the TargetScan, miRTarBase, and miRDB databases, we predicted miRNA target genes and constructed a miRNA-mRNA regulatory network. Furthermore, using the Gene Ontology and KEGG databases we performed functional enrichment and protein-protein interaction analyses. Real-time quantitative polymerase chain reaction (qPCR) and other methods were employed to verify the mRNA expression of related genes. Results: The Morris water maze test revealed that mice exposed to chronic alcohol exhibited a significantly reduced learning ability compared to the control group (p < 0.05). Compared with the control group, the activity of mitochondrial ATPase in the hippocampal tissue of alcohol-treated mice was significantly decreased (p < 0.01), suggesting brain injury. In the model group, H2S significantly increased in the mice hippocampi (p < 0.01), indicating that chronic alcohol exposure could activate cystathionineß-synthase (CBS) and catalyze the mass formation of H2S, suggesting brain injury. A total of 208 differentially expressed miRNAs and 377 differentially expressed mRNAs were screened through bioinformatic analysis. Enrichment analysis indicated that the main pathways were involved in neurodegeneration and regulation of the Wnt signaling pathway. The PCR detected a significant downregulation in the expressions of FOS and EGR1 genes. Discussion: Consequently, chronic alcohol exposure may regulate the expression of FOS and EGR1 in the hippocampus through miR-222-3p, miR-132-3p, miR-212-3p, and miR-191-5p, reduce the activity of hippocampal mitochondrial ATPase, activate CBS, catalyze the large amount of H2S formation, and destroy the mitochondrial structure, resulting in decreased learning ability. Our findings revealed valuable genes and miRNAs for the study of chronic alcohol exposure.

7.
Front Med ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39266905

RESUMEN

Treatment options for patients with esophageal squamous cell carcinoma (ESCC) often result in poor prognosis and declining health-related quality of life. Screening FDA-approved drugs for cancer chemoprevention is a promising and cost-efficient strategy. Here, we found that dronedarone, an antiarrhythmic drug, could inhibit the proliferation of ESCC cells. Moreover, we conducted phosphorylomics analysis to investigate the mechanism of dronedarone-treated ESCC cells. Through computational docking models and pull-down assays, we demonstrated that dronedarone could directly bind to CDK4 and CDK6 kinases. We also proved that dronedarone effectively inhibited ESCC proliferation by targeting CDK4/CDK6 and blocking the G0/G1 phase through RB1 phosphorylation inhibition by in vitro kinase assays and cell cycle assays. Subsequently, we found that knocking out CDK4 and CDK6 decreased the susceptibility of ESCC cells to dronedarone. Furthermore, dronedarone suppressed the growth of ESCC in patient-derived tumor xenograft models in vivo. Thus, our study demonstrated that dronedarone could be repurposed as a CDK4/6 inhibitor for ESCC chemoprevention.

8.
Drug Des Devel Ther ; 18: 4017-4027, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39258273

RESUMEN

Objective: Ciprofol is a novel anesthetic agent, its efficacy and safety had been verified and its clinical implementation has been expanded. However, the knowledge about ciprofol in children is meager. The aim of study is to evaluate the safety and effectiveness of ciprofol in general anesthesia in children undergoing adenoidectomy and adenotonsillectomy, compared with propofol. Materials: We retrospectively analyzed data of children who underwent adenoidectomy or adenotonsillectomy with general anesthesia from June to August 2023 to evaluate the safety and effectiveness of ciprofol. The primary outcomes included hemodynamic changes during induction and postoperative complications in post-anesthesia care unit. The secondary outcomes were extubation time, pediatric anesthesia emergence delirium (PAED) score. Meanwhile, subgroup analysis was performed based on age. Results: 301 children met the inclusion criteria, 157 received ciprofol induction and 144 received propofol. Patient demographics and operation-related information were similar in the two groups. However, the dosage of dexmedetomidine in the propofol group was significantly higher than that of the ciprofol group (p=0.001). The trends of hemodynamic shift during induction and intubation were the same in the two groups. The PAED scores on post-extubation 10min and 20min were significantly reduced in the ciprofol group (p<0.001 and p=0.046). Moreover, in the ≤72 months and the >72 months subgroups, the scores were also significantly lower in the ciprofol group on post-extubation 10min. With the score of >10, the incidence of emergence delirium of the ciprofol group was significantly lower on post-extubation 10min and 20min in the population and the ≤72 months subgroups (p=0.03 and p=0.02). There were no obvious postoperative complications in both groups. Conclusion: Ciprofol exhibited advantageous characteristics in the induction of children, such as stable hemodynamics, a relatively lower incidence of postoperative delirium without apparent post-anesthesia complications. Ciprofol may emerge as a novel option for general anesthesia in pediatric patients.


Asunto(s)
Adenoidectomía , Anestesia General , Tonsilectomía , Humanos , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Niño , Adenoidectomía/efectos adversos , Anestesia General/efectos adversos , Tonsilectomía/efectos adversos , Propofol/administración & dosificación , Propofol/efectos adversos , Complicaciones Posoperatorias , Lactante , Estudios de Cohortes
9.
Artículo en Inglés | MEDLINE | ID: mdl-39265182

RESUMEN

Despite extensive investigation into estrogen's role in pulmonary hypertension (PH) development, its effects-whether beneficial or detrimental-remains contentious. This study aimed to elucidate estrogen's potential role in PH under normoxic and hypoxic conditions. Utilizing norfenfluramine- and hypoxia-induced rat models of PH, the study evaluated the impact of 17ß-estradiol (E2) on PH progression. E2 promoted PH development under normoxia while providing protection under hypoxia. Mechanistically, under normoxia, E2 upregulated methyltransferase-like 3 (METTL3) gene transcription and protein via an estrogen response element-dependent pathway, which in turn elevated the m6A methylation and translational efficiency of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) mRNA, leading to increased PFKFB3 protein levels and enhanced proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Conversely, under hypoxia, E2 downregulated METTL3 transcription through a hypoxia response element-dependent mechanism, driven by elevated hypoxia-induced factor 1α (HIF-1α) levels, resulting in reduced PFKFB3 protein expression and diminished PASMCs proliferation and migration. Both METTL3 and PFKFB3 proteins are upregulated in the pulmonary arteries of patients with PAH. Collectively, these findings suggest that E2 exerts differential effects on PH progression via dual regulation of the METTL3/PFKFB3 protein under normoxic and hypoxic conditions, positioning the METTL3/PFKFB3 protein as a potential therapeutic target for PH treatment.

10.
Clin Exp Rheumatol ; 2024 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-39263792

RESUMEN

OBJECTIVES: To explore whether the balance of CD226 and TIGIT is disturbed in CD3+CD56-TCRαß+CD4-CD8- (DN) T cells and have a better understanding of the potential role of DN T cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: The percentage of DN T cells as well as the expression of CD226 and TIGIT was identified by flowmetry. After in vitro stimulation, we further detected the expression of activation and cytotoxic marker, as well as intracellular cytokines secreted by DN T cells. RESULTS: DN T cells were found to expand in the peripheral blood of pSS patients (1.77±0.66%) and correlate with IgG (r=0.451, p<0.05), C3 (r=-0.438, p<0.05) and C4 (r=-0.470, p<0.05). Imbalanced CD226/TIGIT was observed on peripheral DN T cells of pSS patients, especially the overexpression of inhibitory immunoreceptor TIGIT. The expression ratio of TIGIT and CD226 on DN T cells was elevated in pSS patients and correlated with ESSDAI scores≥5 (r=0.743, p<0.05). Besides, these DN T cells were found to be activated and show strong cytotoxicity. CONCLUSIONS: The balance between CD226 and TIGIT on DN T cells was disturbed and correlated with the disease activity in pSS patients, which may be implicated in the pathogenesis of pSS.

11.
Eur J Clin Nutr ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191954

RESUMEN

OBJECTIVE: We intended to reveal the joint effects between LAE and uPDI on cognition in Chinese older adults. METHODS: Data were collected from the Chinese Longitudinal Healthy Longevity Survey. In total, 10,617 individuals aged 65 years and above without cognitive impairment or dementia at baseline were enrolled in 2008 and followed up in 2011, 2014, and 2018. The uPDI and the scores of LAE were derived from survey responses, and both were categorized into three groups (low, intermediate, and high). Individuals with a Mini-Mental State Examination (MMSE) score lower than 18 were considered to have cognitive impairment. Cox proportional hazards models were employed to explore the joint association of uPDI and LAE on cognitive impairment, followed by restricted cubic spline (RCS) to observe the effects of the continuous-type variable of uPDI and the scores of LAE on the risk of cognitive impairment. Stratified analysis was applied to examine the association of LAE with cognitive impairment in uPDI groups (high uPDI vs. low uPDI). RESULTS: Compared to participants maintained low scores of LAE and high uPDI, those who maintained high scores of LAE and low uPDI had a decreased risk of cognitive impairment (HR = 0.52, 95% CI, 0.43-0.62). The findings of the stratified analysis demonstrated that the protective effects of high scores of LAE on cognition was pronounced in individuals with low uPDI (HR = 0.61, 95% CI: 0.47-0.79) and those with high uPDI (HR = 0.63, 95% CI: 0.51-0.78). CONCLUSIONS: In this cohort study, a higher score of uPDI, which indicated higher intake of salt-preserved vegetables, sugars, and refined grains, was associated with an increased risk of cognitive impairment, whereas this association may be mitigated by regular engagement in leisure activities.

12.
Exp Ther Med ; 28(4): 378, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39113909

RESUMEN

The present systematic review and meta-analysis aimed to generate high-quality evidence on the association between preterm delivery (PTD) and subsequent risk of renal disease in the mother. A literature search was conducted on PubMed, Embase, CENTRAL and Scopus until the 15th of May 2023 for studies reporting an adjusted association between PTD and the risk of maternal renal disease. A total of seven studies were eligible. The pooled analysis found that women with PTD had a statistically significant increased risk of chronic kidney disease in the long term [hazard ratio (HR): 1.82 95% confidence interval (CI): 1.38, 2.40; I2=85%]. Similarly, the meta-analysis also found a statistically significant increased risk of end-stage renal disease (ESRD) amongst women with PTD as compared with those without PTD (HR: 2.22 95% CI: 1.95, 2.53; I2=0%). Overall, the pooled analysis showed a significantly higher incidence of renal disorders with PTD (HR: 1.98; 95% CI: 1.57, 2.50; I2=88%). The results were unchanged on sensitivity analysis. Women with PTD could be at increased risk of future chronic kidney disease and ESRD. The small number of studies and retrospective nature of data are important limitations. Further studies are needed to supplement the available evidence.

13.
Plant Sci ; 348: 112213, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39117001

RESUMEN

Soil salinization, especially in arid environments, is a leading cause of land degradation and desertification. Excessive salt in the soil is detrimental to plants. Plants have developed various sophisticated regulatory mechanisms that allow them to withstand adverse environments. Through cross-adaptation, plants improve their resistance to an adverse condition after experiencing a different kind of adversity. Our analysis of Ammopiptanthus nanus, a desert shrub, showed that mechanical wounding activates the biosynthesis of jasmonic acid (JA) and abscisic acid (ABA), enhancing plasma membrane H+-ATPase activity to establish an electrochemical gradient that promotes Na+ extrusion via Na+/H+ antiporters. Mechanical wounding reduces K+ loss under salt stress, improving the K/Na and maintaining root ion balance. Meanwhile, mechanical damage enhances the activity of antioxidant enzymes and the content of osmotic substances, working together with cellular ions to alleviate water loss and growth inhibition under salt stress. This study provides new insights and approaches for enhancing salt tolerance and stress adaptation in plants by elucidating the signaling mechanisms of cross-adaptation.


Asunto(s)
Homeostasis , Raíces de Plantas , Tolerancia a la Sal , Raíces de Plantas/metabolismo , Raíces de Plantas/fisiología , Ciclopentanos/metabolismo , Clima Desértico , Oxilipinas/metabolismo , Ácido Abscísico/metabolismo , Sodio/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , ATPasas de Translocación de Protón/metabolismo
14.
Sci Rep ; 14(1): 19071, 2024 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154046

RESUMEN

The calcium-binding protein S100A9 has emerged as a pivotal biomolecular actor in oncology, implicated in numerous malignancies. This comprehensive bioinformatics study transcends traditional boundaries, investigating the prognostic and therapeutic potential of S100A9 across diverse neoplastic entities. Leveraging a wide array of bioinformatics tools and publicly available cancer genomics databases, such as TCGA, we systematically examined the S100A9 gene. Our approach included differential expression analysis, mutational burden assessment, protein interaction networks, and survival analysis. This robust computational framework provided a high-resolution view of S100A9's role in cancer biology. The study meticulously explored S100A9's oncogenic facets, incorporating comprehensive analyses of its relationship with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration across various tumor types. This study presents a panoramic view of S100A9 expression across a spectrum of human cancers, revealing a heterogeneous expression landscape. Elevated S100A9 expression was detected in malignancies such as BLCA (Bladder Urothelial Carcinoma), CESC (Cervical squamous cell carcinoma and endocervical adenocarcinoma), COAD (Colon adenocarcinoma), ESCA (Esophageal carcinoma), and GBM (Glioblastoma multiforme), while reduced expression was noted in BRCA (Breast invasive carcinoma), HNSC (Head and Neck squamous cell carcinoma), and KICH (Kidney Chromophobe). This disparate expression pattern suggests that S100A9's role in cancer biology is multifaceted and context-dependent. Prognostically, S100A9 expression correlates variably with patient outcomes across different cancer types. Furthermore, its expression is intricately associated with TMB and MSI in nine cancer types. Detailed examination of six selected tumors-BRCA, CESC, KIRC (Kidney renal clear cell carcinoma), LUSC (Lung squamous cell carcinoma), SKCM (Skin Cutaneous Melanoma); STAD (Stomach adenocarcinoma)-revealed a negative correlation of S100A9 expression with the infiltration of most immune cells, but a positive correlation with neutrophils, M1 macrophages, and activated NK cells, highlighting the complex interplay between S100A9 and the tumor immune environment. This bioinformatics synthesis posits S100A9 as a significant player in cancer progression, offering valuable prognostic insights. The data underscore the utility of S100A9 as a prognostic biomarker and its potential as a therapeutic target. The therapeutic implications are profound, suggesting that modulation of S100A9 activity could significantly impact cancer management strategies.


Asunto(s)
Calgranulina B , Biología Computacional , Neoplasias , Humanos , Calgranulina B/genética , Calgranulina B/metabolismo , Biología Computacional/métodos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Metilación de ADN , Inestabilidad de Microsatélites , Mutación , Mapas de Interacción de Proteínas/genética
15.
Drug Resist Updat ; 77: 101139, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39178713

RESUMEN

Herein, we first isolated two MCR-9- and KPC-2-co-producing K. pneumoniae isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS903B, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.

16.
Ecotoxicol Environ Saf ; 284: 116869, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39178759

RESUMEN

BACKGROUND: Diesel exhaust particles (DEPs), a predominant component of ambient particulate matter (PM), are classified as ultrafine particles with the capacity to penetrate the cerebral blood-brain barrier (BBB). This penetration is implicated in the pathogenesis of central nervous system (CNS) disorders. The integrity of the BBB is inextricably linked to cerebrovascular homeostasis and the development of neurodegenerative disease, highlighting the importance of studying the effects and mechanisms of DEPs on BBB function damage. METHODS AND RESULTS: Utilizing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we explored the detrimental effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an upregulation in the secretion of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, , and diminished tight junction (TJ) protein expression. Microarray analysis revealed that 23 miRNAs were upregulated and 11 were downregulated in response to a 50 µg/mL DEPs treatment, with miR-466d-3p being notably differentially expressed. Wnt3 was identified as a target of miR-466d-3p, with the Wnt signaling pathway being significantly enriched. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/ß-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and ß-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression. CONCLUSIONS: Our study further confirmed that DEPs can induce the disruption of BBB integrity through inflammatory processes. We identified alterations in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a key regulator of tight junction (TJ) proteins, essential for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ ß-catenin and Wnt/PCP signaling pathway can be activated by DEPs and are regulated by miR-466d-3p. Under the combined effects of Wnt/PCP and inflammation, there is an ultimate increase in BBB hyperpermeability. METHODS AND RESULTS: Employing mouse cerebral microvascular endothelial cells (bEnd.3 cells) as an in vitro model of the BBB, we investigated the adverse effects of DEPs exposure on BBB permeability and integrity, with particular focus on inflammation, cell apoptosis, and miRNA expression profiles. Our findings revealed that exposure to DEPs at varying concentrations for 48 h resulted in the inhibition of bEND.3 cell proliferation, induction of cell apoptosis, and an increase in the release of inflammatory cytokines/chemokines and adhesion molecules. The BBB integrity was further compromised, as evidenced by a decrease in trans-epithelial electrical resistance(TEER), a reduction in cytoskeletal F-actin, loss of intercellular junctional organization, and diminished tight junction (TJ) protein expression. Microarray analysis disclosed that 23 miRNAs were upregulated and 11 were downregulated in bEND.3 cells treated with 50 µg/mL DEPs compared to the controls. In particular, miR-466d-3p was identified as a significantly differentially expressed miRNA. Wnt3 was predicted to be a target of miR-466d-3p, and the Wnt signaling pathway was identified as one of the most significantly enriched pathways. We validated that miR-466d-3p expression was downregulated, and the protein expression levels of Wnt/ß-catenin and Wnt/PCP signaling components were elevated. The modulation of the Wnt signaling pathway by miR-466d-3p was demonstrated by the transfection of miR-466d-3p mimic, which resulted in a downregulation of Wnt3 and ß-catenin protein expression, and the mRNA level of Daam1, as well as an enhancement of TJ proteins ZO-1 and Claudin-5 expression. CONCLUSIONS: Our study further confirmed that DEPs can induce the disruption of BBB integrity by inflammation. We identified changes in the expression profile of microRNAs (miRNAs) in endothelial cells, with miR-466d-3p emerging as a regulator of tight junction (TJ) proteins, which are critical for maintaining BBB integrity. Additionally, our findings primarily demonstrated that the Wnt/ ß-catenin and Wnt/PCP signaling pathway can be activated by DEPs and is regulated by miR-466d-3p, and under the combined effects of Wnt/PCP and inflammation ultimately led to hyperpermeability BBB.

17.
Cell Prolif ; : e13695, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39086110

RESUMEN

Retinal ischemia/reperfusion injury (RI/R) is a common pathological process in ophthalmic diseases, which can cause severe visual impairment. The mechanisms underlying RI/R damage and repair are still unclear. Scholars are actively exploring effective intervention strategies to restore impaired visual function. With the development of nucleic acid nanomaterials, tetrahedral framework nucleic acids (tFNAs) have shown promising therapeutic potential in various fields such as stem cells, biosensors, and tumour treatment due to their excellent biological properties. Besides, miRNA-22-3p (miR-22), as an important regulatory factor in neural tissue, has been proven to have positive effects in various neurodegenerative diseases. By stably constructing a complex of tetrahedral framework nucleic acids miR22 (tFNAs-miR22), we observed that tFNAs-miR22 had a positive effect on the repair of RI/R injury in retinal neural tissue. Previous studies have shown that tFNAs can effectively deliver miR-22 into damaged retinal neurons, subsequently exerting neuroprotective effects. Interestingly, we found that there was a certain synergistic effect between tFNAs and miR-22. tFNAs-miR22 can selectively activated the ERK1/2 signalling pathway to reduce neuronal apoptosis, accelerate cell proliferation, and restore synaptic functional activity. In this study, we established a simple yet effective small molecule drug for RI/R treatment which may become a promising neuroprotectant for treating this type of vision impairment disease in the future.

18.
Phytochem Anal ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103224

RESUMEN

INTRODUCTION: Schisandrae Chinensis Fructus (SCF), a traditional Chinese medicine, has been used in treating virtual injury and strain since ancient times. The Chinese Pharmacopoeia reveals that SCF includes raw (RSCF) and vinegar-processed (VSCF) decoction pieces. OBJECTIVE: This study developed an effective method combining the electronic eye (e-eye), electronic tongue (e-tongue), and chemometrics to discriminate RSCF and VSCF from the perspective of chemical composition, color, and taste. MATERIAL AND METHODS: First, RSCF were collected and processed into VSCF, and their color parameters, e-tongue sensory properties, high-performance liquid chromatography (HPLC) and ultra-HPLC (UPLC) characteristic fingerprints, and nominal ingredients were determined. Multivariate statistical analyses, including principal component, linear discriminant, similarity, and partial least squares discriminant analyses, were conducted. RESULTS: HPLC and UPLC fingerprints were established, demonstrating a > 0.900 similarity. The content determination indicated increased schisantherin A, schisantherin B, and schisandrin A contents in VSCF. The e-eye data demonstrated a > 1.5 total color difference before and after processing ΔE*ab, indicating the significantly changed sample color and appearance before and after processing. The e-tongue technology was used to quantitatively characterize the taste of RSCF and VSCF. The t-test revealed significantly reduced sourness, aftertaste-bitter, and aftertaste-astringent values of SCF after vinegar processing. Principal component and partial least squares discriminant analyses indicated that e-eye and e-tongue realize the rapid RSCF and VSCF identification. CONCLUSION: The proposed comprehensive strategy of electronic eye and electronic tongue combined with chemometrics demonstrated satisfactory results with high efficiency, accuracy, and reliability. This can be developed into a novel and accurate method for discriminating RSCF and VSCF.

19.
Nat Mater ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107570

RESUMEN

Ion transport is essential to energy storage, cellular signalling and desalination. Polymers have been explored for decades as solid-state electrolytes by either adding salt to polar polymers or tethering ions to the backbone to create less flammable and more robust systems. New design paradigms are needed to advance the performance of solid polymer electrolytes beyond conventional systems. Here the role of a helical secondary structure is shown to greatly enhance the conductivity of solvent-free polymer electrolytes using cationic polypeptides with a mobile anion. Longer helices lead to higher conductivity, and random coil peptides show substantially lower conductivity. The macrodipole of the helix increases with peptide length, leading to larger dielectric constants. The hydrogen bonding of the helix also imparts thermal and electrochemical stability, while allowing for facile dissolution back to monomer in acid. Peptide polymer electrolytes present a promising platform for the design of next-generation ion-transporting materials.

20.
JAMA Ophthalmol ; 142(8): e241225, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39145830

RESUMEN

This case report describes a diagnosis of streaky multifocal choroiditis in a boy who presented with distorted vision in his left eye for 3 years.


Asunto(s)
Coroiditis , Angiografía con Fluoresceína , Coroiditis Multifocal , Humanos , Masculino , Niño , Coroiditis/diagnóstico , Coroiditis/tratamiento farmacológico , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Agudeza Visual
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